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Abstract Background Laccase (LAC) gene family plays a pivotal role in plant lignin biosynthesis and adaptation to various stresses. Limited research has been conducted on laccase genes in common beans. Results 29 LAC gene family members were identified within the common bean genome, distributed unevenly in 9 chromosomes. These members were divided into 6 distinct subclades by phylogenetic analysis. Further phylogenetic analyses and synteny analyses indicated that considerable gene duplication and loss presented throughout the evolution of the laccase gene family. Purified selection was shown to be the major evolutionary force through Ka / Ks. Transcriptional changes of PvLAC genes under low temperature and salt stress were observed, emphasizing the regulatory function of these genes in such conditions. Regulation by abscisic acid and gibberellins appears to be the case for PvLAC3, PvLAC4, PvLAC7, PvLAC13, PvLAC14, PvLAC18, PvLAC23, and PvLAC26, as indicated by hormone induction experiments. Additionally, the regulation of PvLAC3, PvLAC4, PvLAC7, and PvLAC14 in response to nicosulfuron and low-temperature stress were identified by virus-induced gene silence, which demonstrated inhibition on growth and development in common beans. Conclusions The research provides valuable genetic resources for improving the resistance of common beans to abiotic stresses and enhance the understanding of the functional roles of the LAC gene family.

Abstract Background The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. Methods This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. Results 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p

This study focuses on the application of in-situ laser-assisted single-point diamond turning (ILAT) on SiCp/Al metal matrix composites (MMCs), renowned for their exceptional mechanical properties and difficult-to-cut nature. The surface and subsurface response to the in-situ laser assistance under a small uncut chip thickness (UCT) is investigated. The results demonstrate that appropriate laser energy can reduce subsurface crystal defects while maintaining surface quality during machining. As the laser power increases, the surface damage pattern shifts from cut-through to fracture, eventually leading to severe matrix deformation. Slight compressive stress is observed on the Al phase of surfaces machined with either conventional single-point diamond turning (SPDT) or ILAT. Al crystals near the machined surface and SiC particles in the SPDT sample exhibit a notable accumulation of dislocations. Laser assistance is beneficial for mitigating dislocations and improving the crystalline integrity of Al grains, while Al grains close to the machined surface in both SPDT and ILAT samples present comparable amounts of stacking faults. The findings enhance the understanding of surface and subsurface generation of SiCp/Al composites in ILAT, providing a reference for the application of ILAT on other MMCs.

Abstract Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8+ T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

Abstract The poor prognosis observed in elderly individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains a serious clinical burden and the underlying mechanism is unclear, which necessities detailed investigation of disease characteristics and research for efficient countermeasures. To simulate lethal coronavirus disease 2019 (COVID‐19) in senescent human patients, 80‐week‐old male hamsters are intranasally inoculated with different doses of SARS‐CoV‐2 Omicron BA.5 variant. Exposure to a low dose of the Omicron BA.5 variant results in early activation of the innate immune response, followed by rapid viral clearance and minimal lung damage. However, a high dose of BA.5 results in impaired interferon signaling, cytokine storm, uncontrolled viral replication, and severe lung injury. To decrease viral load and reverse the deterioration of COVID‐19, a new bio‐mimic decoy called CoVR‐MV is used as a preventive or therapeutic agent. Administration of CoVR‐MV as a preventive or therapeutic intervention in the early stages of infection can effectively suppress viral load, regulate the immune response, and rescue animals from death and critical illness. These findings underscore the risk associated with SARS‐CoV‐2 Omicron BA.5 exposure in senescent hamsters and highlight the importance of early intervention to prevent disease progression.

Developing general resilience measures that take into account spatio-temporal dynamics to withstand the adverse effects of shocks on the economy is urgent during the COVID-19 pandemic. However, rapid perception of city economic resilience at large scales is currently a challenge during disasters. Using machine learning to massively simulate hourly anthropogenic NO2 emissions from 2016 to 2020, a resilience quantification framework based on an undesired output perspective is proposed to assess the resilience of Chinese cities’ economic operations during the COVID-19 pandemic. The results show that NO2 can characterize economic activity except for the primary industry. Spatially, the economic resilience of Chinese cities at different stages of the pandemic showed a binary pattern of Huanyong Hu line divergence and north-south divergence, respectively. Temporally, economic resilience had a hysteresis effect. Moreover, cities with larger economies recovered more quickly, despite being hit harder. Measurement of economic resilience based on undesired output required integration of information on fluctuations and trends in emissions. Our study provides a new tool for perceiving resilience during disasters from an undesired output perspective to provide support and insight into city management and planning in the post-pandemic era.

ABSTRACTThe increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults (n = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMTS112 = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.

W-band (75–110 GHz) is a potential radio frequency band to provide long-distance wireless links for mobile data transmission. This paper proposes and experimentally demonstrates high-speed wireless transmission at W-band using photonics-aided method, including optical heterodyne, photonics-aided down-conversion without RF oscillator and coherent detection. A comparison between the photonics-aided method and the conventional electronic method employing solid-state electronic devices is conducted for the first time. The photonics-aided method is shown to offer advantages such as lower harmonic components, spur, reduced nonlinearity, and no local oscillator leakage, results in a 2.5 dB better performance of the photonic-aided W-band mm-wave transmitter compared to the electronic one. In the terms of receiver, the photonics-aided method can surpass the electronic method, with the help of larger electro-optical modulator bandwidth and lower drive voltage in the photonic down-conversion stage. Ultimately, using the photonics-aided method, a recorded equivalent transmission distance of 29 km@84 GHz and 45km@75.6GHz is achieved respectively for 1Gbaud QPSK signal.

ObjectiveGastric cancer (GC) is the world’s third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration.MethodsWe assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05).ResultsWe found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren’s type cells, T cells (CD4+ and CD8+), and CD68+ macrophages in the TME. Kaplan–Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor.ConclusionOur study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

Market participants can only bid with lagged information disclosure under the existing market mechanism, which can lead to information asymmetry and irrational market behavior, thus influencing market efficiency. To promote rational bidding behavior of market participants and improve market efficiency, a novel electricity market mechanism based on cloudedge collaboration is proposed in this paper. Critical market information, called residual demand curve, is published to market participants in real-time on the cloud side, while participants on the edge side are allowed to adjust their bids according to the information disclosure prior to closure gate. The proposed mechanism can encourage rational bids in an incentive-compatible way through the process of dynamic equilibrium while protecting participants' privacy. This paper further formulates the mathematical model of market equilibrium to simulate the process of each market participant's strategic bidding behavior towards equilibrium. A case study based on the IEEE 30-bus system shows the proposed market mechanism can effectively guide bidding behavior of market participants, while condensing exchanged information and protecting privacy of participants.

Abstract Enhancing energy-environmental efficiency (EEE) is crucial for achieving energy conservation and emission reduction goals. Investigating the mechanism through which green technology innovation (GTI) affects EEE and understanding the role of environmental regulation (ER) in this process provides a theoretical basis for efficient utilization of GTI and ER. This study employs a Dynamic Spatial Durbin Model and utilizes panel data from 2003 to 2017 for 30 Chinese provinces to examine the impact of GTI on EEE in the presence of ER. The empirical results reveal: (1) GTI has a U-shaped impact on EEE, primarily driven by SubGI. (2) GTI’s influence on EEE is predominantly reflected in PTE, also stemming from SubGI. (3) The interaction term between ER and GTI is 0.0022, while the GTI coefficient is − 0.0741, and the GTI quadratic term coefficient is 0.0007, all statistically significant. This implies that ER mitigates the negative impact of GTI on EEE while strengthening its positive effect. These findings provide empirical evidence and policy insights for more effectively utilizing GTI and ER to enhance EEE and achieve energy conservation and emissions reduction goals.

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice—responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Rhinoviruses (RVs) are major causes of the common cold and are related to severe respiratory tract diseases, leading to a considerable economic burden and impacts on public health. Available and stable viral resources of rhinoviruses for laboratory use are important for promoting studies on rhinoviruses and further vaccine or therapeutic drug development. Reverse genetic technology can be useful to produce rhinoviruses and will help to promote studies on their pathogenesis and virulence. In this study, rhinovirus A89, an RV-A species that has been found to be highly involved in hospitalization triggered by RV infections, was selected to construct an infectious clone based on its sequence as a representative. The viral mRNA produced by a T7 RNA transcript system was transfected into H1-HeLa cells, and the rescued RV-A89 viruses were harvested and confirmed by sequencing. The rescued RV-A89 induced a similar cytopathic effect (CPE) and shared almost identical growth kinetics curves with parental RV-A89. Moreover, 9A7, a prescreened monoclonal antibody against the parental RV-A89, had a good and specific reaction with the rescued RV-A89, and further characterization showed almost the same morphology and protein composition of both viruses; thus, recombinant RV-A89 with similar biological characterization and virulence to the parental virus was obtained. In summary, the infectious clone of RV-A89 was successfully established, and the development of reverse genetic technology for rhinovirus will provide a framework for further studies on rhinoviruses.

Abstract Background Varicella zoster virus (VZV), which is a human restricted alpha-herpesvirus, causes varicella (chickenpox) and zoster (shingles). The subsequent post-herpetic neuralgia (PHN) due to VZV infection is excruciating for most patients. Thus, developing specific therapeutics against VZV infection is imperative. RNA interference (RNAi) represents an effective approach for alternative antiviral therapy. This study aimed to develop a novel anti-VZV therapeutics based on RNAi. Results In this study, we screened and found the open reading frame 7 (ORF7) of the VZV genome was an ideal antiviral target based on RNAi. Therefore, a novel siRNA targeting ORF7 (si-ORF7) was designed to explore the potential of RNAi antiviral treatment strategy toward VZV. We used a bio-engineering approach to manufacture recombinant siRNA agents with high yield in E. coli. Then, the efficacy of recombinant ORF7-siRNA (r/si-ORF7) in inhibiting VZV infection both in cellular level and 3D human epidermal skin model was evaluated. The r/si-ORF7 was proved to inhibit the VZV replication and reduce the virus copy numbers significantly in vitro. Furthermore, flexible nano-liposomes were established to deliver r/si-ORF7 to 3D human epidermal skin model and found r/si-ORF7 also could inhibit the VZV infection, thus maintaining normal skin morphology. Conclusions Taken together, our results highlighted that transdermal administration of antiviral r/si-ORF7 was a promising therapeutic strategy for functional cure of VZV infection.

Abstract The dual functions of TMEM16F as Ca2+-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca2+-activated Cl- channel. Here, we report evidence for a lipid scrambling pathway along a groove harboring a lipid trail outside the ion permeation pore. This groove contains the binding pocket for niclosamide and 1PBC. Mutations of two residues in this groove specifically affect lipid scrambling. Whereas mutations of some residues in the binding pocket of niclosamide and 1PBC reduce their inhibition of TMEM16F-mediated Ca2+ influx and PS exposure, other mutations preferentially affect the ability of niclosamide and/or 1PBC to inhibit TMEM16F-mediated PS exposure, providing further support for separate pathways for ion permeation and lipid scrambling.

Citrus tristeza virus (CTV) is a globally pervasive and economically significant virus that negatively impacts citrus trees, leading to substantial reductions in fruit yield. CTV occurs within the phloem of infected plants, causing a range of disease phenotypes, such as stem pitting (SP), quick decline (QD), and other detrimental diseases. Research on CTV is challenging due to the large size of its RNA genome and the diversity of CTV populations. Comparative genomic analyses have uncovered genetic diversity in multiple regions of CTV isolates’ genomes, facilitating the classification of the virus into distinct genotypes. Despite these challenges, notable advancements have been made in identifying and controlling CTV strains through serological and molecular methods. The following review concentrates on the techniques of nucleic acid identification and serological analysis for various CTV isolates, assisting in the comparison and evaluation of various detection methods, which are crucial for the effective management of CTV diseases, and so contributes to the innovation and development of CTV detection methods.

Arbuscular mycorrhizal (AM) fungi can enhance the uptake of soil nutrients and water by citrus, promoting its growth. However, the specific mechanisms underlying the action of AM fungi in promoting the growth of citrus were not fully elucidated. This study aimed to explore the role of AM fungi Funneliformis mosseae in the regulatory mechanisms of P. trifoliata growth. Pot experiments combined with non-targeted metabolomics methods were used to observe the growth process and changes in metabolic products of P. trifoliata under the conditions of F. mosseae inoculation. The results showed that F. mosseae could form an excellent symbiotic relationship with P. trifoliata, thereby enhancing the utilization of soil nutrients and significantly promoting its growth. Compared with the control, the plant height, stem diameter, number of leaves, and aboveground and underground dry weight in the F. mosseae inoculation significantly increased by 2.57, 1.29, 1.57, 4.25, and 2.78 times, respectively. Moreover, the root system results confirmed that F. mosseae could substantially promote the growth of P. trifoliata. Meanwhile, the metabolomics data indicated that 361 differential metabolites and 56 metabolic pathways were identified in the roots of P. trifoliata and were inoculated with F. mosseae. This study revealed that the inoculated F. mosseae could participate in ABC transporters by upregulating their participation, glycerophospholipid metabolism, aminoacyl tRNA biosynthesis, tryptophan metabolism and metabolites from five metabolic pathways of benzoxazinoid biosynthesis [mainly enriched in lipid (39.50%) and amino acid-related metabolic pathways] to promote the growth of P. trifoliata.

Abstract The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Background/purpose: Intravenous sedation with propofol in the dental treatment offers an alternative to inhalation sedation or general anesthesia. The aim of this study was to evaluate the safety and identify risk factors for intraoperative complications. Materials and methods: Uncooperative children who could not complete dental treatment under non-pharmacological behavior management or mild-to-moderate sedation in the outpatient pediatric department were selected. Details and time of dental treatment; intraoperative vital signs data, including blood pressure, heart rate, respiratory rate, pulse oxygen saturation (SpO2), end-tidal carbon dioxide, and electrocardiogram; and incidence of intraoperative and postoperative complications were recorded. Results: Overall, 344 children were selected, with 342 completing dental treatment. The dental treatment time was 20–155 (median, 85; interquartile range, 70–100) min. The number of treated teeth was at least 1 and at most 13 (median, 6; interquartile range, 5–8). Among 342 children, 35 (10.2%) had their treatment interrupted temporarily due to choking cough. No serious complications occurred; the incidence rate of minor complications was 47/342 (13.7%). Tachycardia was observed in 5/342 (1.5%) cases, oxygen desaturation (SpO2 < 95%) in 18, and hypoxemia (SpO2 ≤ 90%) in 25. The treatment duration was significant longer in cases with than without complications (P

As a new resource food in China, acer truncatum seed oil is rich in oleic acid, linoleic acid and neuroic acid and other components, and their nutritional value and medicinal health care effects are prominent, which has been increasingly valued by the industry and consumers. In recent years, the new preparation and application development technology of Acer truncatum seed oil has been continuously presented. It has not only been developed for food, but also appeared successively in the flavoring of Acer truncatum seed oil, complex dairy products,tablet candy, etc. It has also been applied in the fields of daily chemical industry, medical care and so on. This paper reviewed the current research progress and the existing problems in the preparation, efficacy evaluation, industrial application and development, and putted forward some suggestions for these problems, which could promote the development and perfection of Acer truncatum seed oil industry.

This study analyzes the use of ride-hailing and bus services from a multi-modal user perspective by jointly modeling individuals’ monthly frequency of use of both bus and ride-hailing services. A bivariate ordered probit model is estimated to capture the influence of socio-demographic and attitudinal characteristics as well as unobserved factors that may simultaneously influence the travel frequency by both modes. We use data collected in a survey of travelers from Porto Alegre, Brazil. The results characterize the profile of local frequent ride-hailing users as young, medium-income, self-employed individuals with a propensity toward the use of technology and a low inclination for car ownership. Most importantly, we observe that after controlling for unobserved factors that simultaneously contribute to higher trip frequencies by both modes, frequent bus users demonstrate a lower propensity toward ride-hailing use.

ABSTRACT Viral vector vaccine represents one of the important research directions of novel vaccines. Viral vectors can efficiently deliver foreign genes and drive robust transgene expression in vivo. Generally, viral vector vaccines can achieve high immunogenicity and rapid response to a new pandemic. However, few types of viral vectors have been thoroughly evaluated for vaccine development, and the application of viral vectors is often limited by packaging capacity, vector immunogenicity, or pre-existing immunity. Cytomegalovirus (CMV) has been regarded as a promising novel vaccine vector because it has the advantages of high package capacity, good safety profiles, and the capacity to induce long-lasting immune responses. In this study, a luciferase-tagged reporter murine CMV (MCMV) was constructed, and the viral dissemination feature in vivo was studied. Furthermore, MCMVs expressing three structural proteins of SARS-CoV-2 were constructed and used to immunize mice. The level of binding antibodies and neutralizing antibodies against the original Wuhan strain and the Omicron variant (BA.2) was compared. Moreover, the CMV vector’s transmission capacity and pre-existing immunity’s influence on CMV-vectored vaccine efficacy were studied. The results showed that CMV vector could only cause transient systemic, but not persistent, infection. Immunization of CMV-vectored vaccines was able to elicit neutralizing antibodies against the Omicron variant (BA.2). However, the titer of neutralizing antibodies against BA.2 is much lower when compared with the original strain. The studies also showed that the CMV vectors would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. Collectively, the CMV-vectored vaccine represents a promising approach to developing novel vaccines against epidemic pathogens. IMPORTANCE Cytomegalovirus (CMV) has been used as a novel viral vector for vaccine development and gene therapy. Coronavirus disease 2019 is an infectious disease caused by the SARS-CoV-2 virus, which is highly mutable and is still circulating globally. The study showed that the CMV viral vector caused transient systemic infection and induced robust transgene expression in vivo. CMV vectors expressing different SARS-CoV-2 proteins were immunogenic and could elicit neutralizing antibodies against a highly mutated Omicron variant (BA.2). The expression level of receptor-binding domain (RBD) protein was higher than that of full-length S protein using CMV as a vaccine vector, and CMV vector expression RBD protein elicited higher RBD-binding and neutralizing antibodies. Moreover, the study showed that CMV-vectored vaccines would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. These works provide meaningful insights for the development of a CMV-based vector vaccine platform and the prevention and control strategies for SARS-CoV-2 infection.

Medium chain triglycerides has the effect of reducing body weight, regulating lipid metabolism, relieving fatigue and so on, and it is liquid at room temperature. In order to facilitate its application in the field of food, the medium chain triglycerides microcapsules were prepared by spray drying with whey protein and inulin as composite wall materials. The effects of composite wall material proportion, wall material addition amount, core-wall ratio, emulsifier addition amount and composite emulsifier proportion on the embedding rate of medium chain triglycerides microcapsules were investigated by single factor experiment. Box-Behnken design response surface test was used to optimize the preparation formula of medium chain triglycerides microcapsules, and the basic physical and chemical properties of the prepared medium chain triglyceride microcapsules were determined. The response surface method results showed that the optimal preparation conditions of medium chain triglycerides microcapsules were as follows: whey protein: inulin ratio of 3∶1 (w/w), emulsifier supplemental amount of 0.4 g/100 mL, core wall ratio of 1∶1 (w/w), compound wall material (whey protein and inulin) supplemental amount of 14 g/100 mL, compound emulsifier (monoglycerol∶sodium carboxymethyl cellulose) ratio of 1∶1 (w/w), under this condition, the embedding rate of carbon chain fatty acid triglyceride microcapsules can reach 95%. The medium chain triglycerides microcapsules had good fluidity, dispersibility and solubility. The microcapsules had uniform particle size, the average particle size were 4.43 μm.

Abstract Objective The study’s purpose is to explore the link of serum albumin on renal progression in patients with chronic kidney disease (CKD). Methods This study was a secondary analysis of a prospective cohort study in which a total of 954 participants were non-selectively and consecutively collected from the research of CKD-ROUTE in Japan between November 2010 and December 2011. We evaluated the association between baseline ALB and renal prognosis (initiation of dialysis or 50% decline in eGFR from baseline) and renal function decline (annual eGFR decline) using the Cox proportional-hazards and linear regression models, respectively. We performed a number of sensitivity analyses to ensure the validity of the results. In addition, we performed subgroup analyses. Results The included patients had a mean age of (66.86 ± 13.41) years, and 522 (69.23%) were male. The mean baseline ALB and eGFR were (3.89 ± 0.59) g/dL and (33.43 ± 17.97) ml/min/1.73 m2. The annual decline in eGFR was 2.65 mL/min/1.73 m2/year. 218 (28.9%) individuals experienced renal prognosis during a median follow-up period of 36.0 months. The baseline ALB was inversely linked with renal prognosis (HR = 0.61, 95%CI: 0.45, 0.81) and renal function decline (β = -1.41, 95%CI: -2.11, -0.72) after controlling for covariates. The renal prognosis and ALB had a non-linear connection, with ALB’s inflection point occurring at 4.3 g/dL. Effect sizes (HR) were 0.42 (0.32, 0.56) and 6.11 (0.98, 38.22) on the left and right sides of the inflection point, respectively. There was also a non-linear relationship between ALB and renal function decline, and the inflection point of ALB was 4.1 g/dL. The effect sizes(β) on the left and right sides of the inflection point were -2.79(-3.62, -1.96) and 0.02 (-1.97, 1.84), respectively. Conclusion This study shows a negative and non-linear association between ALB and renal function decline as well as renal prognosis in Japanese CKD patients. When ALB is lower than 4.1 g/dL, ALB decline was closely related to poor renal prognosis and renal function decline. From a therapeutic point of view, reducing the decline in ALB makes sense for delaying CKD progression.

Diabetes is a complex metabolic disease. In recent years, diabetes and its chronic complications have become a health hotspot of global concern. I t is very important to find promising therapeutic targets and directions. Ferroptosis is a new type of programmed cell death that is different from cell necrosis, apoptosis, and autop hagy. Ferroptosis is mainly characterized by iron-dependent lipid peroxidation. With the reduction of the anti-oxidative capacity of cells, the accumulated reactive lipid oxygen species will cause oxidative cell death and lead to ferroptosis at lethal levels. Recent studies have shown that ferroptosis plays an important regulatory role in the initiation and development of diabetes, as well as various complications of diabetes. In this review, we will summ arize new findings related to ferroptosis and diabetic complications and propose ferroptosis as a potential target for treating diabetic complications.

Multi-energy integrations provide great opportunities for economic and efficient resource utilization. In the mean-time, power system operation requires enough flexible resources to deal with contingencies such as transmission line tripping. Besides economic benefits, this paper focuses on the security benefits that can be provided by multi-energy integrations. This paper first proposes an operation scheme to coordinate multiple energy production and local system consumption considering transmission networks. The integrated flexibility model, constructed by the feasible region of integrated demand response (IDR), is then formulated to aggregate and describe local flexibility. Combined with system security constraints, a multi-energy system operation model is formulated to schedule multiple energy production, transmission, and consumption. The effects of local system flexibility on alleviating power flow violations during $N-1$ line tripping contingencies are then analyzed through a multi-energy system case. The results show that local system flexibility can not only reduce the system operation costs, but also reduce the probability of power flow congestion or violations by approximately 68.8% during $N-1$ line tripping contingencies.

The three macronutrients of lipid, protein and carbohydrate are closely related to human health, and their supply is basically sufficient. However, with the increasing number of patients suffered from hyperlipidemia, obesity, etc., as well as the deepening of the aging process, traditional nutrients can not fulfill the nutritional needs of these people anymore. Therefore, nutritional, processing and organoleptic properties of these three major nutrients need to be enhanced by the deep-processing. Nowadays, the recombinant protein and carbohydrate industries have made great progress in China, but the recombinant lipid industry is just in its infancy. Hence, this paper briefly introduced the status, development opportunities and challenges of domestic structure lipid industry，and expounded the underlying efficacy mechanisms of several main structure lipids. The latest research progress on the health effects and preparation technology of structure lipid were also presented. In addition, in view of the existing problems, future development advices are proposed from the perspectives of theoretical breakthrough, technological innovation, and industrial upgrading, aiming to provide valuable references for the development of domestic structure industry.