Enhancing docosahexaenoic acid production from Schizochytrium sp. by using waste Pichia pastoris as nitrogen source based on two-stage feeding control.

To reduce the cost of docosahexaenoic acid (DHA) production from Schizochytrium sp., the waste Pichia pastoris was successfully used as an alternative nitrogen source to achieve high-density cultivation during the cell growth phase. However, due to the high oxygen consumption feature when implementing high-density cultivation, the control of both the nitrogen source and dissolved oxygen concentration (DO) at each sufficient level was impossible; thus, two realistic control strategies, including "DO sufficiency-nitrogen limitation" and "DO limitation-nitrogen sufficiency", were proposed. When using the strategy of "DO sufficiency-nitrogen limitation", the lowest maintenance coefficient of glucose (12.3 mg/g/h vs. 17.0 mg/g/h) and the highest activities of related enzymes in DHA biosynthetic routes were simultaneously obtained; thus, a maximum DHA concentration of 12.8 ± 1.2 g/L was achieved, which was 1.58-fold greater than that of the control group. Overall, two-stage feeding control for alternative nitrogen sources is an efficient strategy to industrial DHA fermentation.

MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Modified EBP-bFGF targeting endogenous renal extracellular matrix protects against renal ischemia-reperfusion injury in rats.

Acute kidney injury (AKI) is a life-threatening disease primarily caused by renal ischemia-reperfusion (I/R) injury, which can result in renal failure. Currently, growth factor therapy is considered a promising and effective approach for AKI treatment. Basic fibroblast growth factor (bFGF), an angiogenic factor with potent activity, efficiently stimulates angiogenesis and facilitates regeneration of renal tissue. However, the unrestricted diffusion of bFGF restricts its clinical application in AKI treatment. Therefore, developing a novel sustained released system for bFGF could enhance its potential in treating AKI. In this study, we genetically engineered a multifunctional recombinant protein by fusing bFGF with a specific peptide (EBP). EBP-bFGF effectively binds to the extracellular matrix in the injured kidney, enabling slow release of bFGF in AKI. Furthermore, following orthotopic injection into I/R rats' ischemic kidneys, EBP-bFGF exhibited stable retention within the tissue. Additionally, EBP-bFGF suppressed apoptosis of renal cells, reduced renal fibrosis, and facilitated recovery of renal function. These findings suggest that EBP-bFGF delivery system represents a promising strategy for treating AKI.

L-tryptophan anaerobic fermentation for indole acetic acid production: Bacterial enrichment and effects of zero valent iron.

Indole acetic acid (IAA) as a plant hormone, was one of the valuable products of anaerobic fermentation. However, the enriching method remained unknown. Moreover, whether zero valent iron (ZVI) could enhance IAA production was unexplored. In this work, IAA producing bacteria Klebsiella (63 %) was enriched successfully. IAA average production rate and concentration were up to 3 mg/L/h and 56 mg/L. With addition of 1 g/L ZVI, IAA average production rate and concentration was increased for 2 and 3 folds. Mechanisms indicated ZVI increased Na+K+-ATP activity and electron transport activity for 2 folds and 1 fold. Moreover, macro transcription determined indole pyruvate pathway activity like primary-amine oxidase, indole pyruvate decarboxylase and aldehyde dehydrogenase were increased for 146 %, 187 %, and 557 %, respectively. Therefore, ZVI was suitable for enhancement IAA production from mixed culture anaerobic fermentation.

Invasive cellular blue nevus in the cervical spine: A case report.

INTRODUCTION: Cellular blue nevus is an uncommon neoplasm in the spine. PATIENT CONCERNS: Here, we present a case of a 24 years old male with a 2 months history of numbness in the right upper limb and shoulder. DIAGNOSIS: Cervical spine and subcutaneous tissue invasive cellular blue nevus. INTERVENTIONS: The patient underwent C4 laminectomy and partial C3 and C5 laminectomy for total resection of the lesion. Histopathology revealed a nodular tumor with unclear boundaries, which was composed of heavily pigmented dendritic cells and more pigmented spindle cells. OUTCOMES: There was no recurrence during 3 years follow-up. CONCLUSION: Invasive cellular blue nevus of the spine can be wrongly diagnosed as spinal meningeal melanocytoma and meningeal melanoma due to its special cell behavior and rarity. Therefore, it is important to understand its pathological and clinical characteristics to avoid over-treatment.

Development and application of a low-priced duplex quantitative PCR assay based on SYBR Green I for the simultaneous detection of porcine deltacoronavirus and porcine sapelovirus.

Porcine deltacoronavirus (PDCoV) and porcine sapelovirus (PSV) are two viruses that can cause diarrhoea in pigs and bring great economic loss to the pig industry. In this research, a duplex real-time quantitative polymerase chain reaction (qPCR) assay based on SYBR Green I was developed to simultaneously detect PDCoV and PSV. No specific melting peaks were found in other porcine diarrhoea-associated viruses, indicating that the method developed in this study had good specificity. The detection limits of PDCoV and PSV were 1.0 × 101 copies µl-1 and 1.0 × 102 copies µl-1, respectively. The duplex real-time qPCR assay tested two hundred and three (203) intestinal and faecal samples collected from diarrhoeal and asymptomatic pigs. The positive rates of PDCoV and PSV were 20.2% and 23.2%, respectively. The co-infection rate of PDCoV and PSV was 13.8%. To evaluate the accuracy of the developed method, conventional PCR and singular TaqMan real-time qPCR assays for PDCoV/PSV were also used to detect the samples. The results showed that the duplex real-time qPCR assay was consistent with the singular assays, but its sensitivity was higher than conventional PCR methods. This duplex real-time qPCR assay provides a rapid, sensitive and reliable method in a clinic to simultaneously detect PDCoV and PSV.

Controllable Preparation of a N-Doped Hierarchical Porous Carbon Framework Derived from ZIF-8 for Highly Efficient Capacitive Deionization.

Capacitive deionization (CDI) is a promising desalination technology, and metal-organic framework (MOF)-derived carbon as an electrode material has received more and more attention due to its designable structure. However, MOF-derived carbon materials with single-pore structures have been difficult to meet the technical needs of related fields. In this work, the ordered hierarchical porous carbon framework (OMCF) was prepared by the template method using zeolitic imidazolate frameworks-8 (ZIF-8) as a precursor. The pore structures, surface properties, electrochemical properties, and CDI performances of the OMCF were investigated and compared with the microporous carbon framework (MCF), also derived from ZIF-8. The results show that the hierarchical porous carbon OMCF possessed a higher specific surface area, better hydrophilic surface (with a contact angle of 13.45°), and higher specific capacitance and ion diffusion rate than those of the MCF, which made the OMCF exhibit excellent CDI performances. The adsorption capacity and salt adsorption rate of the OMCF in a 500 mg·L-1 NaCl solution at 1.2 V and a 20 mL·min-1 flow rate were 12.17 mg·g-1 and 3.34 mg·g-1·min-1, respectively, higher than those of the MCF. The deionization processes of the OMCF and MCF closely follow the pseudo-first-order kinetics, indicating the double-layer capacitance control. This work serves as a valuable reference for the CDI application of N-doped hierarchical porous carbon derived from MOFs.

Fabricating Ru Atom-Doped Novel FeP4/Fe2PO5 Heterogeneous Interface for Overall Water Splitting in Alkaline Environment.

Developing bifunctional electrocatalysts with low-content noble metals and high activity and stability is crucial for water splitting. Herein, we reported a novel Ru doped FeP4/Fe2PO5 heterogeneous interface catalyst (Ru@FeP4/Fe2PO5) for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) by heat treatment coupling electrodeposition strategy. Experiments disclosed that Ru@FeP4/Fe2PO5 proclaimed excellent catalytic activity for the OER (249 mV@100 mA cm-2) and HER (49 mV@10 mA cm-2) in a 1 M KOH environment. More importantly, the mass activity and turnover frequency of Ru@FeP4/Fe2PO5 were 117 and 108 times higher than that of commercial RuO2 at an overpotential of 300 mV during the OER, respectively. In addition, the assembled Ru@FeP4/Fe2PO5 || Ru@FeP4/Fe2PO5 system could retain superior durability in a two-electrode system for 134 h at 300 mA cm-2. Further mechanism studies revealed that Ru atoms in Ru@FeP4/Fe2PO5 act in a key role for the excellent activity during water splitting because the electronic structure of Ru sites could be optimized by the interaction between Ru and Fe atoms at the interface to strengthen the adsorption of reaction intermediates. Besides, the introduction of Ru atoms could also enhance the charge transfer, which effectually accelerates the reaction kinetics. The strategy of anchoring Ru atom on novel heterostructure provides a promising path to boost the overall activity of electrocatalysts for water splitting.

Investigating the Psychological, Social, Cultural, and Religious Predictors of COVID-19 Vaccine Uptake Intention in Digital Age: A Media Dependency Theory Perspective.

Media exposure to health communication contents related to the COVID-19 pandemic alone is inadequate to measure the influence of media on individuals in adopting precautionary behaviors against COVID-19, such as vaccine uptake. Certain individuals may pay attention to and be influenced by communication content. However, literature has suggested other instrumental determinants in developing and adopting health precautionary measures, such as culture or religion, especially regarding vaccination. In times of crisis, such as the COVID-19 pandemic, it is valuable to examine the interrelationships among psychological, sociocultural, and informational factors. This can provide valuable insights for policymakers in developing effective communication strategies. Drawing an analogy between the Media dependency theory (MDT) and the Theory of Planned Behavior (TPB) model, this study unravels the factors underpinning the COVID-19 vaccine uptake intention among Pakistanis. The study utilized a cross-sectional research design and employed a survey method to gather data from a sample of 993 participants. The findings obtained from the PLS-SEM analysis confirmed that individuals relied on both traditional and social media to cope with the COVID-19 pandemic. The findings show that individuals rely more on the informational content disseminated through conventional media channels. The findings also suggest that individuals from Asian countries, such as Pakistan, tend to be more inclined toward collectivism. The findings about the moderating role of religiosity suggest that religious beliefs significantly shape individuals' reliance on traditional media. Hence, this study has uniquely contributed to public health and media management by providing a strategy for managers to address disseminating misinformation related to religion and its impact on vaccination-related health issues. The study has theoretically confirmed the principles of media dependency theory. As a result, it is recommended that various information sources be utilized to cultivate resilience among individuals to manage health crises effectively.

Mapping the Acetylamino and Carboxyl Groups on Glycans by Engineered α-Hemolysin Nanopores.

Glycan is a crucial class of biological macromolecules with important biological functions. Functional groups determine the chemical properties of glycans, which further affect their biological activities. However, the structural complexity of glycans has set a technical hurdle for their direct identification. Nanopores have emerged as highly sensitive biosensors that are capable of detecting and characterizing various analytes. Here, we identified the functional groups on glycans with a designed α-hemolysin nanopore containing arginine mutations (M113R), which is specifically sensitive to glycans with acetamido and carboxyl groups. Molecular dynamics simulations indicated that the acetamido and carboxyl groups of the glycans produce unique electrical signatures by forming polar and electrostatic interactions with the M113R nanopores. Using these electrical features as the fingerprints, we mapped the length of the glycans containing acetamido and carboxyl groups at the monosaccharide, disaccharide, and trisaccharide levels. This proof-of-concept study provides a promising foundation for developing single-molecule glycan fingerprinting libraries and demonstrates the capability of biological nanopores in glycan sequencing.

sccomp: Robust differential composition and variability analysis for single-cell data.

Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

Expression of codon-optimized PDCoV-RBD protein in baculovirus expression system and immunogenicity evaluation in mice.

Porcine deltacoronavirus (PDCoV) is a global epidemic enteropathogenic coronavirus that mainly infects piglets, and causes huge losses to the pig industry. However, there are still no commercial vaccines available for PDCoV prevention and controlment. Receptor-binding domain (RBD) is located at the S1 subunit of PDCoV and is the major target for developing viral inhibitor and vaccine. In this study, the characteristics of the RBD were analyzed by bioinformatic tools, and codon optimization was performed to efficiently express the PDCoV-RBD protein in the insect baculovirus expression system. The purified PDCoV-RBD protein was obtained and fully emulsified with CPG2395 adjuvant, aqueous adjuvant and Al(OH)3 adjuvant, respectively, to develop vaccines. The humoral and cellular immune responses were assessed on mice. The results showed that both the RBD/CPG2395 and RBD/aqueous adjuvant could induce stronger immune responses in mice than that of RBD/Al(OH)3. In addition, the PDCoV challenge infection was conducted and the RBD/CPG2395 could provide better protection against PDCoV in mice. Our study showed that the RBD protein has good antigenicity and can be used as a protective antigen, which provided a basis for the development of the PDCoV vaccine.

User acceptance of smart home voice assistant: a comparison among younger, middle-aged, and older adults.

Voice assistants are widely used in smart home environments. This study aimed to investigate user acceptance of a smart home voice assistant. A questionnaire was designed, and 471 Chinese adults were recruited to complete the questionnaire. The data were analyzed using exploratory factor analysis and regression analysis. The results revealed that user requirements of adults were composed of six factors: hedonic motivation and trust (ß = .41, p < .001), social influence (ß = .22, p < .001), performance expectancy (ß = .15, p < .001), effort expectancy (ß = .08, p = .018), product features (ß = .15, p = .009), and facilitating conditions (ß = .06, p = .049). Among these six factors, hedonic motivation and trust are considered the most important. Younger, middle-aged, and older adults differed significantly in their requirements and acceptance of a smart home voice assistant. These findings have implications for the design of smart home voice assistants so that they are more acceptable to younger and older adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s10209-022-00936-1.

Formation, structure and stability of high internal phase Pickering emulsions stabilized by BSPI-C3G covalent complexes.

Food-grade high internal phase Pickering emulsions (HIPPEs) are stabilized by protein-based particles, which have attracted extensive attention due to their good gel-like structure. The black soybean isolate protein/cyanidin-3-O-glucoside (BSPI-C3G) covalent particles were used as a particulate emulsifier to form stable HIPPEs with oil phase fractions (74 % v/v) and low particle concentrations (0.5 %-3 % w/v) The particle size distribution and microstructure demonstrated that the BSPI-C3G covalent particles acted as an interfacial layer and surrounded the oil droplets. As the concentration of BSPI-C3G particles increased from 0.5 % to 3 %, the droplet size, elasticity, antioxidant capacity of the heated or stored HIPPEs more stable. So, the HIPPEs had the best stability with the BSPI-C3G particle at 3 % (w/v) concentration. These findings may extend the application of BSPI and C3G in foods and provide the guidelines for the rational design of food-grade HIPPEs stabilized by protein/anthocyanin complexes.

Effects of communication style, anthropomorphic setting and individual differences on older adults using voice assistants in a health context.

BACKGROUND: Voice assistants enable older adults to communicate regarding their health as well as facilitate ageing in place. This study investigated the effects of communication style, anthropomorphic setting, and individual differences on the trust, acceptance, and mental workload of older adults using a voice assistant when communicating health issues. METHODS: This is a mixed-methods study utilising both quantitative and qualitative methods. One hundred and six older adults (M = 71.8 years, SD = 4.6 years) participated in a 2 (communication style: social- vs. task-oriented; between-subject)[Formula: see text] 2 (anthropomorphic setting: ordinary profession vs. medical background; within-subject) mixed design experiment. The study used multivariate analysis of variance (MANOVA) to examine the effects of communication style, anthropomorphic setting of the voice assistant, and participants' use frequency of digital devices on the trust, technology acceptance, and mental workload of older adults using a voice assistant in a health context. End-of-study interviews regarding voice assistant use were conducted with participants. Qualitative content analyses were used to assess the interview findings about the communication content, the more trustworthy anthropomorphic setting, and suggestions for the voice assistant. RESULTS: Communication style, anthropomorphic setting, and individual differences all had statistically significant effects on older adults' evaluations of the voice assistant. Compared with a task-oriented voice assistant, older adults preferred a social-oriented voice assistant in terms of trust in ability, integrity, and technology acceptance. Older adults also had better evaluations for a voice assistant with a medical background in terms of trust in ability, integrity, technology acceptance, and mental workload. In addition, older adults with more experience using digital products provided more positive evaluations in terms of trust in ability, integrity, and technology acceptance. CONCLUSIONS: This study suggests that when designing a voice assistant for older adults in the health context, using a social-oriented communication style and providing an anthropomorphic setting in which the voice assistant has a medical background are effective ways to improve the trust and acceptance of older adults of voice assistants in an internet-of-things environment.

Correction: Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates.

Correction for 'Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates' by Ziyang Dong et al., Chem. Commun., 2022, 58, 7980-7983, https://doi.org/10.1039/D2CC02882D.

Development and immunogenicity evaluation of porcine deltacoronavirus inactivated vaccine with different adjuvants in mice.

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in pigs of various ages, especially in suckling piglets, and there are no effective measures to prevent and control PDCoV currently. In this study, two adjuvants Al(OH)3 and ODN2395 working through different mechanisms were used to prepare inactivated PDCoV vaccines, and the immune effects of PDCoV inactivated vaccines were assessed in mice. From the results, we found that both PDCoV/Al(OH)3 vaccine and PDCoV/2395 vaccine could induce IgG and neutralizing antibodies with high levels in mice. At the same time, cytokines of IFN-γ, IL-4 and chemokine ligand of CXCL13 in serum were significantly increased after immunization, and reached the highest levels in PDCoV/2395 vaccine group, which suggested that PDCoV/2395 could promote the production of both Th1 and Th2 polarized cytokines. In addition, histopathological observations showed that vaccination helped mice resist PDCoV infection. These results indicated that both the two inactivated vaccines have good immune effects. Moreover, the PDCoV/2395 vaccine worked better than the PDCoV/Al(OH)3 vaccine for PDCoV/2395 having the good ability to induce both humoral and cellular immunogenicity. The PDCoV/2395 inactivated vaccine developed in this study might be an effective tool for the prevention of PDCoV infection.

Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates.

1,2,3-Thiadiazoles serve as masked S-electrophilic thia-1,3-dipoles. Under rhodium/racemic BINAP catalysis, they undergo denitrogenative (3 + 2) umpolung transannulations with aryl isothiocyanates with inverse regioselectivity and excellent stereoselectivity, yielding N-aryl 3H-1,2-dithiol-(Z)-3-imines in a redox-neutral, step-efficient, and functionality-tolerant manner. An intramolecular S-S bond is impressively forged.

SIK2 Improving Mitochondrial Autophagy Restriction Induced by Cerebral Ischemia-Reperfusion in Rats.

Previous studies have shown that Salt-induced kinase-2(SIK2) is involved in the regulation of various energy-metabolism-related reactions, and it also can regulate angiogenesis after cerebral ischemia-reperfusion. However, it is unclear whether SIK2 can regulate energy metabolism in cerebral ischemia-reperfusion injury. As mitochondria plays an important role in energy metabolism, whether SIK2 regulates energy metabolism through affecting mitochondrial changes is also worth to be explored. In this study, rats were treated with adeno-associated virus-SIK2-Green fluorescent protein (AAV-SIK2-GFP) for the overexpression of SIK2 before middle cerebral artery occlusion (MCAO). We found that SIK2 overexpression could alleviate the neuronal damage, reduce the area of cerebral infarction, and increase the adenosine triphosphate (ATP) content, which could promote the expression of phosphorylated-mammalian target of rapamycin-1 (p-mTORC1), hypoxia-inducible factor-1α (HIF-1α), phosphatase and tensin homologue-induced putative kinase 1 (PINK1) and E3 ubiquitinligating enzyme (Parkin). Transmission electron microscopy revealed that SIK2 overexpression enhanced mitochondrial autophagy. It is concluded that SIK2 can ameliorate neuronal injury and promote the energy metabolism by regulating the mTOR pathway during cerebral ischemia-reperfusion, and this process is related to mitochondrial autophagy.