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Age-related macular degeneration (AMD) is the first permanent cause of vision loss in developed countries, which is also a disease with high incidence and blindness rate in China. Studies have demonstrated that lipid metabolism is one of the key mechanisms of AMD. However, the precise mechanism remains unclear and medications for AMD treatments based on this mechanism have not yet been established. In this review, we critically review relevant studies to examine the associations between lipid metabolism and AMD from the perspectives of lipoproteins, lipid metabolism-related molecular, and lipid metabolism-related treatments, aiming to help understand the roles that lipid metabolism mechanisms play in the development and progression of AMD and to provide ideas for future targeted lipid metabolism therapies.

Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

In view of the natural endowment of mercury in fossil fuels and mineral resources, as well as the mercury emission controlling and regulating in the energy and resource utilization processes, the research and development on the mercury continuous emissions monitoring system (Hg-CEMS) with proprietary intellectual property rights is the most important requirement in science and technology in China. As a critical component of the Hg-CEMS system, the flue gas pretreatment system is a core technology that limits the development and application of the Hg-CEMS technology in China. This paper presents a comprehensive review of the research progress in the four key modules of the Hg-CEMS flue gas pretreatment technology, including the dilution sampling, Hg0/Hg2+ separation, Hg2+ reduction and Hg2+ calibration gas generation. Firstly, the dilution sampling techniques are highlighted in their characteristics and principles. The working principles, structures, and design considerations of the critical parameters for both critical hole and thermal dilution injectors are summarized. Emphasis is focused on the connection of numerical simulation with the optimal design methodology for the thermal dilution injector and critical hole. Secondly, regarding the Hg0/Hg2+ separation technology, various partitioning methodologies encompassing the wet absorption separation, physical adsorption separation and chemical adsorption separation are discussed. Particular attention is given to the separation and adsorption efficiency of the advanced dry chemical adsorption techniques involving the novel selective adsorbents of KCl and CaO with their updated theoretical and experimental outcomes under practical operating conditions. Thirdly, in aspect of the Hg2+ reduction technology, a comparative analysis of wet chemical reduction, low-temperature reduction and high-temperature reduction techniques is expatiated. Particular focus is on the active components of solid-state reducing agents, the impact of temperature on the reduction of divalent mercury, and the detrimental influences of flue gas components on the re-oxidation of the reduced elemental mercury in the low-temperature reduction techniques. An in-depth investigation of the impact of filler materials, acidic gas components and acid removal techniques on the reduction of divalent mercury in the high-temperature reduction techniques is highlighted. Finally, facing the technical problems, a solid generation method of the Hg2+ calibration gas is invented and its industrial utilization feasibility is verified in chemistry and experiments. In conjunction with the current status of research and application of the Hg-CEMS technology, the research technical routs, the solutions to some problems and development prospect for the above-mentioned four key modules are put forward.

ABSTRACT: Infectious laryngotracheitis (ILT) and Newcastle disease (ND) are 2 highly infectious avian respiratory diseases that have caused significant economic losses in the poultry industry worldwide. In ovo vaccination is administered during the late stage of incubation and is an attractive immunization method for poultry industry. However, most of the avian live vaccine strains that are safe for use after hatching are highly pathogenic to chicken embryos and therefore unsafe for in ovo vaccination. Previously, a recombinant Newcastle disease virus (NDV) strain, rTS-gB, expressing the gB protein of Infectious laryngotracheitis virus (ILTV), was demonstrated to be safe and immunogenic as a bivalent vaccine for hatched birds. In this study, we evaluated the safety and protective efficacy of rTS-gB as an in ovo vaccine. This vaccine strain was found to be safe for in ovo vaccination, with a hatchability and survival rate of 93.3% in chickens vaccinated in ovo with rTS-gB. In ovo vaccination with rTS-gB induced effective ILTV- and NDV-specific antibody responses in birds and conferred complete protection against virulent NDV and ILTV challenges. Furthermore, shedding of the challenged ILTV in cloacal and tracheal samples from in ovo vaccinated chickens was greatly reduced. These results indicate that the rNDV strain rTS-gB is a safe and highly immunogenic in ovo vaccine candidate against both ND and ILT.

The industrialization of animal agriculture has undoubtedly contributed to the improvement of human well-being by increasing the efficiency of food animal production. At the same time, it has also drastically impacted the natural environment and human society. The One Health initiative emphasizes the interdependency of the health of ecosystems, animals, and humans. In this paper, we discuss some of the most profound consequences of animal agriculture practices from a One Health perspective. More specifically, we focus on impacts to host-microbe interactions by elaborating on how modern animal agriculture affects zoonotic infections, specifically those of bacterial origin, and the concomitant emergence of antimicrobial resistance (AMR). A key question underlying these deeply interconnected issues is how to better prevent, monitor, and manage infections in animal agriculture. To address this, we outline approaches to mitigate the impacts of agricultural bacterial zoonoses and AMR, including the development of novel treatments as well as non-drug approaches comprising integrated surveillance programs and policy and education regarding agricultural practices and antimicrobial stewardship. Finally, we touch upon additional major environmental and health factors impacted by animal agriculture within the One Health context, including animal welfare, food security, food safety, and climate change. Charting how these issues are interwoven to comprise the complex web of animal agriculture's broad impacts on One Health will allow for the development of concerted, multidisciplinary interventions which are truly necessary to tackle these issues from a One Health perspective.

Purpose: Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. Methods: Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. Results: DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. Conclusion: DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

Background: Medium- to high-risk classification-gastrointestinal stromal tumors (MH-GIST) have a high recurrence rate and are difficult to treat. This study aims to predict the recurrence of MH-GIST within 3 years after surgery based on clinical data and preoperative Delta-CT Radiomics modeling. Methods: A retrospective analysis was conducted on clinical imaging data of 242 cases confirmed to have MH-GIST after surgery, including 92 cases of recurrence and 150 cases of normal. The training set and test set were established using a 7:3 ratio and time cutoff point. In the training set, multiple prediction models were established based on clinical data of MH-GIST and the changes in radiomics texture of enhanced computed tomography (CT) at different time periods (Delta-CT radiomics). The area under curve (AUC) values of each model were compared using the Delong test, and the clinical net benefit of the model was tested using decision curve analysis (DCA). Then, the model was externally validated in the test set, and a novel nomogram predicting the recurrence of MH-GIST was finally created. Results: Univariate analysis confirmed that tumor volume, tumor location, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), diabetes, spicy hot pot, CT enhancement mode, and Radscore 1/2 were predictive factors for MH-GIST recurrence ( P

Abstract In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.

In the photoacoustic detection of breast cancer, the weak intensity and severe energy attenuation of photoacoustic signals excited by the breast tissue become an important factor limiting the efficient acquisition of the ultrasound transducer. To overcome this problem, we proposed a linear defect channel and bifurcated acoustic transmission channel models at the front of the ultrasonic transducers based on the phononic crystal bandgap characteristics and defect state structure. The results of numerical analyses and simulations carried out using COMSOL demonstrated that the photoacoustic signal transmission channel proposed could confine the acoustic energy within the defects, while achieving the directional transmission and local enhancement of the acoustic field of high-frequency breast photoacoustic signals. This design effectively reduces the signal transmission loss and amplifies the mammographic signal intensity, which is conducive to efficient acquisition. In addition, the directional transmission effect is found to be strongly dependent on frequency, which makes the channel have great frequency selectivity. Through the flexible modulation of the transmission path of the artificial acoustic structure, breast photoacoustic signals of specific frequencies can be exported in separate paths to reduce the interference of noise signals. This study combines biomedical tumor detection with phononic crystals to present a novel method for efficient acquisition and deep detection of acoustic signals in tissue photoacoustic detection from the signal perspective, which is conducive to improving the sensitivity of breast cancer detection.

BackgroundPeritoneal fibrosis (PF) is the main complication of peritoneal dialysis (PD) and the most common cause of cessation from PD. There is still no effective therapeutic approach to reserve PF. We aimed to investigate the role of miR-132-3p and underlying potential mechanisms in PF.MethodsA total of 18 Sprague-Dawley (SD) rats were divided randomly into three groups (n = 6): (i)Control group (ii)PF group (iii)PF+Losartan group; Rats in the PF group and PF+Losartan group received daily intraperitoneal injections of 3 mg/kg chlorhexidine for 14 days, and rats in the PF+Losartan group simultaneously received daily intraperitoneal injections of 2 mg/kg losartan for 14 days. The control group was injected with saline in the same volume. Met-5A cells were treated for 24h with TGF-β1 dissolved in recombinant buffered saline at a concentration of 10 ng/ml, meanwhile, PBS solution as a negative control. The human peritoneal solution was collected for the detection of miR-132-3p.ResultsIn vivo, SD rats were infused with chlorhexidine to establish PF model, and we found that miR-132-3p significantly decreased and the expressions of transforming growth factor-β1 (TGF-β1), and Smad2/3 were up-regulated in PF. In vitro, miR-132-3p mimics suppressed TGF-β1/Smad2/3 activity, whereas miR-132-3p inhibition activated the pathway. In human peritoneal solution, we found that the expression of miR-132-3p decreased in a time-dependent model and its effect became more pronounced with longer PD duration.ConclusionMiR-132-3p ameliorated PF by suppressing TGF-β1/Smad2/3 activity, suggesting that miR-132-3p represented a potential therapeutic approach for PF.

Triphenyl phosphate (TPHP) has been widely used as flame retardants and been detected with increasing frequency in environment. TPHP can transform into mono-hydroxylated phosphate (OH-TPHP) and diester diphenyl phosphate (DPHP) through biotransformation. So far, information on the cytotoxicity and molecular regulatory mechanisms of TPHP metabolites are still limit. This study investigated the adverse effects of TPHP, OH-TPHP, and DPHP in HepG2 cells in terms of cell proliferation, lactate dehydrogenase release, reactive oxygen species generation, and mitochondrial membrane potential. The transcriptomic changes were measured using RNA sequencing, and bioinformatics characteristics including biological functions, signal pathways and protein-protein interaction were analyzed to explore the potential molecular mechanisms. Results displayed that the order of cytotoxicity was OH-TPHP> TPHP> DPHP. The prioritized biological functions changes induced by TPHP and OH-TPHP were correlated with lipid metabolism. Significant lipid accumulation was observed as confirmed by increased total cholesterol and triglycerides contents, and enhanced oil red O staining. Enrichment of PPARα/γ and down-stream genes suggested the participation of PPARs signal pathway in lipid metabolism disorder. In addition, TPHP and OH-TPHP induced endoplasmic reticulum stress (ERS), which was further confirmed by the ERS inhibitor experiment. In general, TPHP and OH-TPHP had obvious cytotoxic effects in HepG2 cells. PPARs signal pathway and endoplasmic reticulum stress may be involved in the lipid metabolism disorder induced by TPHP and OH-TPHP.

Abstract Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.

Blood flow is an important physiological parameter of the human body. Real-time measurement of blood flow in the brain, skeletal muscle, and breast tissue is of great significance for disease diagnosis, treatment, surgery, and intensive care. Near-Infrared Diffuse Correlation Spectroscopy (DCS) is a new-type tissue blood flow measurement technology. When using DCS technology for blood flow measurement, the light source-detector (S-D) at each distance contains different degrees of mixed signals of superficial and deep tissues, among which the superficial signals show greater impact on the extraction of blood flow in deep tissues. This paper combines the Nth order linear algorithm (NL algorithm) with the independent component analysis algorithm (Independent Component Analysis, ICA) to separate and process the short-range and long-range optical signals obtained by DCS technology. The computer simulation shows that the algorithm proposed in this paper can better separate the blood flow signals of the superficial and deep tissues, and demonstrates important potential for the application of DCS technology in clinical blood flow measurement in the future.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans. Goal: This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods: With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan University (NCT04275947, B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. The effects of different diagnostic factors were ranked based on the results from a single factor analysis, with 0.05 as the significance level for factor inclusion and 0.1 as the significance level for factor exclusion. Independent variables were selected by the step-forward multivariate logistic regression analysis to obtain the probability model. Findings: We applied the statistical method of a multivariate regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are accessible. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). Discussion: With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results.

Abstract Background Early-life antibiotic exposure is associated with the development of later obesity through the disruption of gut microbiota in the animal models. However, the related epidemiological evidence is still conflicting. Methods A birth cohort was consisted of 2140 mother-infant pairs in Chaoyang District Maternal and Child Health Care Hospital in this study. Here, their available antibiotic exposure during the first one year of life was ascertained using a open-ended questionnaire and related anthropometric parameters from the health screening program. The compositions of gut microbiota were comprehensively analyzed by16S rRNA high throughput sequencing. Then the spearman correlations were performed by the multiple covariance-adjusted regressions between the antibiotic exposure with anthropometric parameters and compositions of gut microbiota. Results Among the 2140 subjects, the antibiotic exposure during the first one year of life was 53.04%, mainly by Cephalosporins (53.39%) and Erythromycins(27.67%) for the treatment of respiratory tract infection (79.56%), which were not significantly different among the subgroups. Compared to the control group, both childhood overweight and obesity at two and a half years were higher in the antibiotic exposed group, with higher percents of Faecalibacterium, Agathobacter and Klebsiella, and lower percentage of Bifidobacterium. Moreover, there were positively potential associations between early-life antibiotic exposure with the accelerated anthropometric parameters and disruption of Faecalibacterium, Agathobacter, Klebsiella and Bifidobacterium at two and a half years. Conclusion These above results proved that early-life antibiotic exposure was positively associated with the accelerated childhood overweight and obesity from one year to two and a half years by impacting the disorders of Faecalibacterium, Agathobacter, Klebsiella and Bifidobacterium, which would propose the theoretical basis for rationalizing the personalized antibiotic exposure among the infants to truly reflect the fairness of public health.

In recent years, energetic molecular perovskites, which serve as an energetic material design platform, have shown potential for designing primary and secondary explosives. To explore their potential in gunpowder and pyrotechnics, this study constructed a new nitrate-bridged molecular perovskite, (H2dabco)[K(NO3)3] (DAN-2, H2dabco2+ ​= ​1,4-diazabicyclo-[2.2.2.]octane-1,4-diium), based on potassium nitrate—a major component of black powder. The single-crystal structure analysis indicated that DAN-2 possesses a cubic perovskite structure in the space group Pm 3¯ m. Theoretical calculations revealed that DAN-2 has an energy level slightly higher than TNT and much higher than black powder. Adding DAN-2 into a typical propellant formulation can increase the impetus while significantly lowering the flame temperature. Moreover, DAN-2 has a lower sensitivity (IS ​= ​29 ​J, FS > 360 ​N) than TNT (IS ​= ​15 ​J, FS ​= ​360 ​N). It is worth mentioning that DAN-2 can avoid the environmental concern of sulfide-induced acid rain since it does not bear any sulfur. Therefore, DAN-2 can be considered a new single explosive and a modern edition of black powder obtained via mixing oxidative KNO3 and a reductive organic fuel at the molecular scale. Furthermore, it displays promising potential in the field of gunpowder and pyrotechnics.

Research on the structural responses to thermal stimuli for crystalline energetic materials is crucial to their practical applications. DAP-4 is a metal-free molecular perovskite high-energetic material attracting increasing attentions on its application potential as heat-resistant explosive. In order to reveal its structural responses to thermal stimuli, herein we investigated the structural phase transitions and thermal expansion of DAP-4 by DSC, single-crystal X-ray diffraction, and variable-temperature capillary powder X-ray diffraction. The results show that DAP-4 undergoes two-step reversible phase transitions at 300.4/298.9 K and 548.4/547.7 K, respectively, which are caused by two-step order-disorder transition of the molecular components during a heating/cooling cycle. The axial and the volumetric expansion coefficients of DAP-4 are estimated based on the temperature-dependent cell parameters obtained by Pawley refinement in a large temperature range of 173–353 K, and they are close to those estimated for β-HMX. Notably, although a volume change of 0.77% occur in the near-room-temperature phase transition, all the crystalline phases of DAP-4 possess cubic structures with isotropic expansibility, rather than the commonly-observed anisotropic one in the most of known energetic crystals, which may be propitious to reduce the adverse effect of its volume change on the formulation design.

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

Acetohydroxyacid synthase (AHAS) is the target of more than 50 commercial herbicides, with many site-of-action resistance isolates identified in weeds. Here, the authors report the structural and kinetic characterizations to explain the effect AHAS mutations have on herbicide potency.

Abstract Background Abnormal expression of long non-coding RNAs (lncRNAs) has been shown to be associated with the pathogenesis of cancers, including colorectal cancer (CRC). It has been reported that LINC00022 is highly expressed in some typs of cancer and its overexpression indicates poor prognosis. The function of LINC00022 in CRC progression remains unclear and is mainly investigated in the present study. Methods LINC00022 expression in CRC tissues was analyzed by using the TNMplot software. LINC00022 expression in CRC cells was measured by quantitative real-time PCR. The effects of LINC00022 on the malignant behaviors of CRC cells were detected by a series of in vitro and in vivo experiments. Dual-luciferase assays were used to verify the targeting relationship between LINC00022 and miR-375-3p and between miR-375-3p and Forkhead box F1 (FOXF1), followed by the rescue experiment. Results LINC00022 was highly expressed in CRC tissues compared with paired para-carcinoma tissues (n = 41). CRC cells with LINC00022 knockdown exhibited decreased cell proliferation, migration, and invasion abilities but increased apoptosis accompanied by decreased protein levels of c-Myc, cyclin D1, cleaved caspase 3, cleaved poly(ADP-ribose) polymerase, matrix metalloproteinase (MMP) 2, and MMP9. Additionally, LINC00022 downregulation in CRC cells suppressed the tube formation of human umbilical vein endothelial cells (HUVECs) as evidenced by decreased vascular endothelial growth factor A levels in LINC00022-silenced cells. The inhibitory effect of LINC00022 knockdown on tumor growth was also observed in an in vivo model. Conversely, LINC00022 overexpression showed that opposite effect. We further demonsrtaed that LINC00022 could upregulate FOXF1 expression through sponging miR-375-3p. Moreover, miR-375-3p knockdown reversed the effects of LINC00022 down-regulation. Conclusions LINC00022 may up-regulate FOXF1 expression via competitively binding miR-375-3p, thereby promoting the development of CRC.

Abstract The effects of polycyclic aromatic hydrocarbons on phytoplankton have been extensively documented, but there is limited knowledge about the physiological responses of marine primary producers to phenanthrene at environmentally relevant levels. Here, we investigated the toxicity of phenanthrene (0, 1, and 5 or 10 μg L−1) to the physiological performance of two cosmopolitan phytoplankton species: the green alga Chlorella vulgaris and bloom-forming diatom Skeletonema costatum. The specific growth rates of both species were remarkably inhibited at both low (1 μg L−1) and high phenanthrene concentrations (5 or 10 μg L−1), while their tolerance to phenanthrene differed. At the highest phenanthrene concentration (10 μg L−1), the growth of C. vulgaris was inhibited by 69%, and no growth was observed for S. costatum cells. The superoxide dismutase activity of both species was enhanced at high phenanthrene concentration, and increased activity of catalase was only observed at high phenanthrene concentration in C. vulgaris. Interestingly, the low phenanthrene concentration stimulated the photosynthetic and relative electron transport rates of S. costatum, whereas hormetic effects were not found for growth. Based on our results, phenanthrene could be detrimental to these two species at a environmentally relevant level, while different tolerance levels were detected.

Novel goose parvovirus (NGPV), a genetic variant of goose parvovirus, has been spreading throughout China since 2015 and mainly infects ducklings with the symptoms of growth retardation, beak atrophy, and protruding tongue, leading to huge economic losses every year. A safe and effective vaccine is urgently needed to control NGPV infection. In this study, virus-like particles (VLPs) of NPGV were assembled and evaluated for their immunogenicity. The VP2 protein of NGPV was expressed in Spodoptera frugiperda insect cells using baculovirus as vector. The VP2 protein was efficiently expressed in the nucleus of insect cells, and the particles with a circular or hexagonal shape and a diameter of approximately 30 nm, similar to the NGPV virion, were observed using transmission electron microscopy (TEM). The purified particles were confirmed to be composed of VP2 using western blot and TEM, indicating that the VLPs of NGPV were successfully assembled. Furthermore, the immunogenicity of the VLPs of NGPV was evaluated in Cherry Valley ducks. The level of NGPV serum antibodies increased significantly at 1–4 weeks post-immunization. No clinical symptoms or deaths of ducks occurred in all groups after being challenged with NGPV at 4 weeks post-immunization. There was no viral shedding in the immunized group. However, viral shedding was detected at 3–7 days post-challenge in the non-immunized group. Moreover, VLPs can protect ducks from histopathological lesions caused by NGPV and significantly reduce viral load in tissue at 5 days post-challenge. Based on these findings, NGPV VLPs are promising candidates for vaccines against NGPV.

With the increasing awareness of environmental protection, it is necessary to develop natural product extracts as antifouling (AF) agents for alternatives to toxic biocides or metal-based AF paints to control biofouling. This paper briefly summarizes the latest developments in the natural product extracts and their derivatives or analogues from marine microorganisms to terrestrial plants as AF agents in the last five years. Moreover, this paper discusses the structures–activity relationship of these AF compounds and expands their AF mechanisms. Inspired by the molecular structure of natural products, some derivatives or analogues of natural product extracts and some novel strategies for improving the AF activity of protective coatings have been proposed as guidance for the development of a new generation of environmentally friendly AF agents.

Porous thermal insulation materials (PTIMs) are a class of materials characterized by low thermal conductivity, low bulk density and high porosity. The low thermal conductivity of the gas enclosed in their pores allows them to achieve efficient thermal insulation, and are they among the most widely used and effective materials in thermal insulation material systems. Among the PTIMs, polyurethane foam (PUF) stands out as particularly promising. Its appeal comes from its multiple beneficial features, such as low density, low thermal conductivity and superior mechanical properties. Such attributes have propelled its broad application across domains encompassing construction, heterogeneous chemical equipment, water conservation and hydropower, and the aviation and aerospace fields. First, this article outlines the structure and properties of porous thermal insulation PUF materials. Next, it explores the methods of preparing porous thermal insulation PUF materials, evaluating the associated advantages and disadvantages of each technique. Following this, the mechanical properties, thermal conductivity, thermal stability, and flame-retardant characteristics of porous thermal insulation PUF materials are characterized. Lastly, the article provides insight into the prospective development trends pertaining to porous thermal insulation PUF materials.

Abstract Background With the rapid advances of genetic and genomic technologies, the pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) were gradually becoming clear, however, the prognosis of IPF was still poor. This study aimed to systematically explore the ferroptosis-related genes model associated with prognosis in IPF patients. Methods Datasets were collected from the Gene Expression Omnibus (GEO). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to create a multi-gene predicted model from patients with IPF in the Freiburg cohort of the GSE70866 dataset. The Siena cohort and the Leuven cohort were used for validation. Results Nineteen differentially expressed genes (DEGs) between the patients with IPF and control were associated with poor prognosis based on the univariate Cox regression analysis (all P

Abstract Background and aims Atherosclerosis is a vital cause of cardiovascular diseases. The correlation between proteinuria and atherosclerosis, however, has not been confirmed. This study aimed to assess whether there is a relationship between proteinuria and atherosclerosis. Methods From January 2016 to September 2020, 13,545 asymptomatic subjects from four centres in southern China underwent dipstick proteinuria testing and carotid atherosclerosis examination. Data on demography and past medical history were collected, and laboratory examinations were performed. The samples consisted of 7405 subjects (4875 males and 2530 females), excluding subjects failing to reach predefined standards and containing enough information. A multivariate logistic regression model was used to adjust the influence of traditional risk factors for atherosclerosis on the results. Results Compared with proteinuria-negative subjects, proteinuria-positive subjects had a higher prevalence rate of carotid atherosclerosis. The differences were statistically significant (22.6% vs. 26.7%, χ2 = 10.03, p = 0.002). After adjusting for common risk factors for atherosclerosis, age, sex, BMI, blood lipids, blood pressure, renal function, hypertensive disease, diabetes mellitus and hyperlipidaemia, proteinuria was an independent risk factor for atherosclerosis (OR = 1.191, 95% CI 1.015–1.398, p = 0.033). The Hosmer–Lemeshow test was used to test the risk prediction model of atherosclerosis, and the results showed that the model has high goodness of fit and strong independent variable prediction ability. Conclusions Proteinuria is independently related to carotid atherosclerosis. With the increase in proteinuria level, the risk of carotid atherosclerotic plaque increases. For patients with positive proteinuria, further examination of atherosclerosis should not be ignored.

To investigate the mechanical properties and constitutive equation of pressed CL−20 based aluminized explosives, the stress-strain curves at different strain rates are obtained by quasi-static and dynamic compression tests using universal testing machine and Split Hopkinson Pressure Bars (SHPB), respectively. The results suggest that the quasi-static and dynamic compression process of pressed CL−20 based aluminized explosives can be divided into elastic stage, hardening stage, and strain soften. In the process quasi-static compression, the pressed CL−20 based aluminized explosives have obvious strain rate effects. As the strain rate increases, the elastic modulus and ultimate strength increase, while the critical strain decrease, and the elastic stress basically remains unchanged. Under dynamic compression, strain rate effects are not obvious in the initial stage when the strain is less than 0.01. When the strain is larger than 0.01, there is a significant strain rate effects, causing the elastic stress, elastic modulus and ultimate strength to increase as dynamic loading strain rate increasing. In addition, the constitutive equations under quasi-static and dynamic compression are described by power-exponential hardening model and ZWT model, and the test results of which are in good agreement with the model calculations, indicating that the two model can be used to describe the mechanical properties of a pressed CL−20 based aluminized explosives.

Solid pseudopapillary neoplasm (SPN) of the pancreas is rare relatively low-grade malignant neoplasm and metastasis rarely. Surgical resection is the primary treatment option for primary and metastatic lesions of SPN, and chemotherapy is often ineffective in non-operable SPNs. SPNs are characterized by the presence of somatic CTNNB1 exon 3 mutations, leading to the activation of Wnt/β-catenin/Cox-2 signal pathway. Here, we firstly report that a refractory liver metastatic pancreatic SPN patient after the failure of multi-line chemotherapies benefited from the Cox-2 selective inhibitor (Celecoxib) based on CTNNB1 D32V mutation detected by next-generation sequencing (NGS), achieving a more than 22-month progression-free survival without any adverse events. Our case provides a potential treatment option for liver metastatic SPN patients with CTNNB1 mutations and highlights the application of NGS for the better treatment decision making.

Conventional acoustic systems exhibit a difficulty in sensing weak acoustic fault signals in complex mechanical vibration environments. Therefore, it is necessary to develop an acoustic sensing mode and a corresponding functional device with pressure amplification. This paper proposes a three-dimensional device, coupling gradient acoustic metamaterials (GAM) with phononic crystals (GAM–PC). The strong wave compression effect coupled with the phononic crystal equivalent medium mechanism is utilized to achieve the enhancement of weak acoustic signal perception at the target frequency. The superior amplification capability of the GAM–PC structure for the amplitude of loud signals is verified by numerical simulations and experiments. Moreover, the GAM–PC structure has a narrower bandwidth per slit, making it more frequency selective. Furthermore, the structure can separate different frequency components. This work is expected to be applied to signal monitoring in environments with strong noise.

The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally.

Herbicides are commonly deployed as the front-line treatment to control infestations of weeds in native ecosystems and among crop plants in agriculture. However, the prevalence of herbicide resistance in many species is a major global challenge. The specificity and effectiveness of herbicides acting on diverse weed species are tightly linked to targeted proteins. The conservation and variance at these sites among different weed species remain largely unexplored. Using novel genome data in a genome-guided approach, 12 common herbicide-target genes and their coded proteins were identified from seven species of Weeds of National Significance in Australia: Alternanthera philoxeroides (alligator weed), Lycium ferocissimum (African boxthorn), Senecio madagascariensis (fireweed), Lantana camara (lantana), Parthenium hysterophorus (parthenium), Cryptostegia grandiflora (rubber vine), and Eichhornia crassipes (water hyacinth). Gene and protein sequences targeted by the acetolactate synthase (ALS) inhibitors and glyphosate were recovered. Compared to structurally resolved homologous proteins as reference, high sequence conservation was observed at the herbicide-target sites in the ALS (target for ALS inhibitors), and in 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (target for glyphosate). Although the sequences are largely conserved in the seven phylogenetically diverse species, mutations observed in the ALS proteins of fireweed and parthenium suggest resistance of these weeds to ALS-inhibiting and other herbicides. These protein sites remain as attractive targets for the development of novel inhibitors and herbicides. This notion is reinforced by the results from the phylogenetic analysis of the 12 proteins, which reveal a largely consistent vertical inheritance in their evolutionary histories. These results demonstrate the utility of high-throughput genome sequencing to rapidly identify and characterize gene targets by computational methods, bypassing the experimental characterization of individual genes. Data generated from this study provide a useful reference for future investigations in herbicide discovery and development.

The molecular perovskite energetic materials (H2dabco)[NH4(ClO4)3] (DAP-4, H2dabco2+ = 1,4-diazabicyclo[2.2.2]octane-1,4-diium), limits its separate application in explosives duo to the severe negative oxygen balance. Therefore, it is of great significance to study the thermal decomposition performance of DAP-4 in the presence of AP oxidant. In this work, the differential scanning calorimetry-thermogravimetry-mass spectrometry-fourier transform infrared spectroscopy (DSC-TG-MS-FTIR) coupling technique, thermal decomposition kinetics, and in-situ FTIR method were used to analyze the thermal decomposition characteristics, and the variation of condensed phase characteristic groups of DAP-4 and the DAP-4/AP mixtures. The results show that AP has negligible effect on thermal decomposition temperature of DAP-4 but can prolong the total decomposition time of DAP-4 by 5.55 min. In addition, thermal decomposition of AP and DAP-4 in the mixture is independent of each other, and the thermal decomposition mechanism of DAP-4/AP mixtures is more complicated than that of DAP-4 alone. Thermal decomposition of DAP-4/AP mixture firstly experiences decomposition of AP at low temperature, the inside crystal transformation of DAP-4, the H+ transfer, and then cage skeleton collapse-induced redox reaction to generate large amount of heat which can shift forward the high-temperature decomposition peak of AP.

Abstract The function of M‐Phase Phosphoprotein 9 (MPHOSPH9) has not been investigated in gastric cancer yet. In the present study, the public cancer databases Oncomine and TCGA were analyzed, and MPHOSPH9 was found upregulated in gastric cancer tumor tissues. Immunohistochemistry (IHC) was also carried out to further confirm the results, and IHC analysis showed MPHOSPH9 was elevated in tumor tissues compared with the paracancerous tissues. QRT‐PCR analysis also revealed that MPHOSPH9 mRNA was upregulated in gastric cancer cell lines. In addition, Kaplan–Meier estimates showed gastric cancer patients with high MPHOSPH9 level predicted a poor prognosis. Then, Western blot and CCK‐8 assay showed overexpressed MPHOSPH9 enhanced gastric cancer cell proliferation, but MPHOSPH9 knockdown suppressed gastric cancer cell proliferation. Additionally, Western blot showed that MPHOSPH9 regulated the activation of mTOR, and overexpressed MPHOSPH9 reduced the inhibitory effects of mTOR inhibitors on cell survival in gastric cancer cells. Taken together, our results suggested that MPHOSPH9 .could be an oncogene in gastric cancer by regulating mTOR signaling.

Antifouling substances play a crucial role in inhibiting fouling and adhesion due to their broad-spectrum and non-toxic advantages. Nevertheless, the excessive release of the antifouling agents shortens the service life of the antifouling coating. In this study, we investigated the antifouling performance of an ethanol extract from the root of Stellera chamaejasme (Sc) through algal adhesion experiments. The interaction between Sc and algae (Chlorella and Dunaliella tertiolecta) was further studied by using a UV spectrophotometer. Then, Sc was encapsulated with polydopamine (PDA) microcapsules to prepare Sc@SiO2@PDA microcapsules by the template method. The release behavior of Sc@SiO2@PDA under different pH conditions was investigated. The result demonstrates that the interaction between Sc and algae belongs to single static quenching, and the Sc@SiO2@PDA microcapsules exhibit good antifouling performance against Chlorella and Dunaliella tertiolecta. This work will provide guiding significance for the development of eco-friendly marine antifouling coatings.

Molecular perovskite energetic crystals, as an emerging family of promising practicable energetic materials, have attracted increasing attentions in the past few years. Different from the mainstream strategies focusing on the intra-molecular designs and modifications on fused-ring energetic molecules/ions, molecular perovskites rely on the self-assembly of diverse molecular components into specified ternary crystal structures, hence generally could be prepared via an easy scale-up process at a low cost. As a kind of ternary salts, they have some unique advantages on the energetic-material designs in terms of optimizing oxygen balance, increasing pack efficiency (and crystal density), and decreasing hygroscopicity, hence could achieve improved detonation performances meanwhile overcome some technical weaknesses of traditional energetic binary salts. In this review, we summarize the current findings and understandings on molecular perovskite energetic crystals, and provide an outlook for the new opportunities brought by this new and promising material family towards advanced multi-component energetic crystals.

Abstract Background Interstitial lung diseases (ILDs), a diverse group of diffuse lung diseases, mainly affect the lung parenchyma. The low-throughput ‘omics’ technologies (genomics, transcriptomics, proteomics) and relative drug information have begun to reshaped our understanding of ILDs, whereas, these data are scattered among massive references and are difficult to be fully exploited. Therefore, we manually mined and summarized these data at a database (ILDGDB, http://ildgdb.org/ ) and will continue to update it in the future. Main body The current version of ILDGDB incorporates 2018 entries representing 20 ILDs and over 600 genes obtained from over 3000 articles in four species. Each entry contains detailed information, including species, disease type, detailed description of gene (e.g. official symbol of gene), and the original reference etc. ILDGDB is free, and provides a user-friendly web page. Users can easily search for genes of interest, view their expression pattern and detailed information, manage genes sets and submit novel ILDs-gene association. Conclusion The main principle behind ILDGDB’s design is to provide an exploratory platform, with minimum filtering and interpretation, while making the presentation of the data very accessible, which will provide great help for researchers to decipher gene mechanisms and improve the prevention, diagnosis and therapy of ILDs.

In ovo vaccination is an attractive immunization strategy for the poultry industry. However, although most live Newcastle disease virus (NDV) vaccine strains, such as LaSota and V4, can be used after hatching, they are pathogenic to chicken embryos when administered in ovo. We have previously reported that NDV strain TS09-C is a safe in ovo vaccine in specific-pathogen-free and commercial chicken embryos because it is attenuated in chicken embryos. However, the molecular basis of its attenuation is poorly understood. In this study, we firstly evaluated the safety of chimeric NDV strains after exchanging genes between strains TS09-C and LaSota as in ovo vaccines, and demonstrated that the attenuation of NDV in chicken embryos was dependent upon the origin of the fusion (F) protein. Next, by comparing the F protein sequences of TS09-C strain with those of LaSota and V4 strain, the R115 in cleavage site and F379 were found to be unique to TS09-C strain. The mutant viruses were generated by substituting one or two amino acids at position 115 and 379 in the F protein, and their safety as in ovo vaccine was evaluated. Mutation in residue 379 did not affect the viral embryonic pathogenicity. While the mutant virus rTS-2B (R115G mutation based on the backbone of TS09-C strain) with two basic amino acids in F cleavage site, was pathogenic to chicken embryos and similar with rLaSota in its tissue tropism, differing markedly from rTS09-C with three basic amino acids in F cleavage site. Together, these findings indicate that the F protein cleavage site containing three basic amino acids is the crucial determinant of the attenuation of TS09-C in chicken embryos. This study extends our understanding of the pathogenicity of NDV in chicken embryos and should expedite the development of in ovo vaccines against NDV.

Maternally derived antibodies (MDA) substantially interfere with active immunity in post-hatch vaccination, although they provide early protection against disease through passive immunity in young chickens. Previously, Newcastle disease virus (NDV) strain TS09-C was demonstrated to be safe and immunogenic as in-ovo vaccine in specific-pathogen-free chickens. Here, we evaluated the safety, protective efficacy, and duration of clinical protection of the TS09-C virus as an in-ovo vaccine for commercial chickens in the presence of Maternally derived antibodies against NDV. This vaccine was safe in commercial chickens and provided at least 80% protection against a virulent NDV challenge for 3 mo, despite inducing a low hemagglutinin-inhibition titer. For commercial chickens, the protective efficacy of the in-ovo vaccination was markedly higher than that of posthatch vaccination, and the cellular immune response might play an important role in the higher protective efficacy of the in-ovo vaccine. The overall results indicate that the maternally derived antibodies against NDV do not significantly interfere with the ability of the in-ovo vaccine strain TS09-C to induce protective cellular immunity.