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Abstract Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRT‒PCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.

Objective The Pingbei slope belt is one of the key zones for the exploration of lithologic reservoirs in the Xihu Depression. However, the exploration process was inhibited by issues of small thickness and significant lateral variation of sand-bodies. Therefore, research on the tectonic-sedimentary response, including the stratigraphic development patterns, deposition center evolution, and sand-body distribution mechanisms in different tectonic units, is urgently needed. Methods Integrating the newly obtained well drilling, well logging, and high-resolution 3D seismic data, a high-precision sequence stratigraphic framework was established and the third-order sequences and systems tracts were analysed in the Pinghu Formation of the Pingbei slope belt. Results Based on differences in palaeogeomorphology and fault systems, the tectonic-sedimentary units of the Pingbei slope zone were classified. Differences in fault styles, stratigraphic contact relationships, and sedimentary filling patterns under different sequence stratigraphic architectures were analysed in various tectonic units. Additionally, the controlling factors and models of sand-body distribution in various sequence stratigraphic architectures were discussed. Conclusion This study revealed that the Pingbei slope zone can be divided into four types of sequence stratigraphic architectures: steep fault slope, opposite fault step, reversal step fault, and forward step fault. The sequence stratigraphic architectures that were controlled by factors of sediment supply, fault activity, palaeogeomorphic, and base-level cycles generated four sand-body distribution models. Research on the differences in sequence configurations and sand-body distribution models in different tectonic units is important for promoting the exploration of lithological reservoirs in the Pingbei slope belt of the Xihu Depression.

Abstract The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.

Gas adsorption and separation/desorption are two pivotal stages in gas capture, demanding additional energy for liberating gas molecules from the adsorbent. Hence, it’s essential to engineer an adsorbent with minimal energy consumption yet effective gas adsorption–desorption characteristics. Accordingly, this research introduces a carbon nano-network (CNN) material capable of inhaling and exhaling gases via self-deformation. Molecular dynamics simulations demonstrate that the gas adsorption–desorption capabilities of CNN can be efficiently regulated by its deformation. While the size of CNN minimally affects the gas sorption rate, a larger CNN necessitates a prolonged duration to achieve saturation under identical gas conditions. Incorporating elongated appendages in CNN enhances both its stability during contraction and its efficiencies in gas adsorption and desorption. We discerned that attaining a critical gas density within a confined space is imperative to initiate self-desorption of CNN. Specifically, if the gas density dips below this critical threshold–set at 5.2 times that of CO2 at room temperature (300 K) and atmospheric pressure (1 Bar)–CNN exhibits no self-desorption capability. Nevertheless, even a marginal elevation in gas density triggers and maintains self-desorption with a consistently surpassing desorption ratio of 98 %. This discovery offers valuable insights for designing automatic self-desorption materials or apparatuses.

Background: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City. Methods: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region. Results: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023. Conclusion: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain.

Abstract To investigate the hypolipidemic and modulation effects of probiotics, the golden hamster of hyperlipidemia model was established and intervened with Lactobacillus fermentum GLF‐217 (GLF‐217) and lovastatin (LOV) for 6 weeks. Body weight and serum biochemical indexes were measured, and liver, colonic contents, and feces were collected after autopsy for pathological and gut microbiota analysis. The results showed that the intervention of GLF‐217 and LOV could significantly reduce serum lipid levels and liver fat accumulation in golden hamsters on a high‐fat diet, more importantly, the LOV intervention could cause damage to the liver. The LOV intervention significantly reduced the contents of short‐chain fatty acids (SCFAs) in the colonic and downregulated the abundance of SCFAs‐producing bacteria, but GLF‐217 intake increased butyric acid, thus reducing blood lipids and protected the liver. This study elucidates the possible mechanism of the hypolipidemic effect of probiotics in terms of regulating gut microbiota.

Abstract Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Nafion membranes are widely used as proton exchange membranes, but their proton conductivity deteriorates in high-temperature environments due to the loss of water molecules. To address this challenge, we propose the utilization of porous aromatic frameworks (PAFs) as a potential solution. PAFs exhibit remarkable characteristics, such as a high specific surface area and porosity, and their porous channels can be post-synthesized. Here, a novel approach was employed to synthesize a PAF material, designated as PAF-45D, which exhibits a specific surface area of 1571.9 m2·g−1 and possesses the added benefits of facile synthesis and a low cost. Subsequently, sulfonation treatment was applied to PAF-45D in order to introduce sulfonic acid groups into its pores, resulting in the formation of PAF-45DS. The successful incorporation of sulfonic groups was confirmed through TG, IR, and EDS analyses. Furthermore, a novel Nafion composite membrane was prepared by incorporating PAF-45DS. The Nyquist plot of the composite membranes demonstrates that the sulfonated PAF-45DS material can enhance the proton conductivity of Nafion membranes at high temperatures. Specifically, under identical film formation conditions, doping with a 4% mass fraction of PAF-45DS, the conductivity of the Nafion composite membrane increased remarkably from 2.25 × 10−3 S·cm−1 to 5.67 × 10−3 S·cm−1, nearly 2.5 times higher. Such promising and cost-effective materials could be envisioned for application in the field of Nafion composite membranes.

Most of vaccinees and COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, which helps preventing infection and alleviating symptoms. However, breakthrough viral infections caused by emerging SARS-CoV-2 variants, especially Omicron subvariants, still pose a serious threat to global health. By monitoring the viral infections and the sera neutralization ability of a long-tracked cohort, we found out that the immune evasion of emerging Omicron subvariants and the decreasing neutralization led to the mini-wave of SARS-CoV-2 breakthrough infections. Meanwhile, no significant difference had been found in the infectivity of tested SARS-CoV-2 variants, even though the affinity between human angiotensin-converting enzyme 2 (hACE2) and receptor-binding domain (RBDs) of tested variants showed an increasing trend. Notably, the immune imprinting of inactivated COVID-19 vaccine can be relieved by infections of BA.5.2 and XBB.1.5 variants sequentially. Our data reveal the rising reinfection risk of immune evasion variants like Omicron JN.1 in China, suggesting the importance of booster with updated vaccines.

BackgroundIn recent investigations, substantial strides have been made in the precise modulation of the gut microbiota to prevent and treat a myriad of diseases. Simultaneously, the pressing issue of widespread antibiotic resistance and multidrug resistance resulting from Shigella infections demands urgent attention. Several studies suggest that the antagonistic influence of the gut microbiota could serve as a novel avenue for impeding the colonization of pathogenic microorganisms or treating Shigella infections. However, conventional research methodologies encounter inherent challenges in identifying antagonistic microbial agents against Shigella, necessitating a comprehensive and in-depth analysis of the causal relationship between Shigella infections and the gut microbiota.Materials and methodsUtilizing the aggregated summary statistics from Genome-Wide Association Studies (GWAS), we conducted Mendelian Randomization (MR) analyses encompassing 18,340 participants to explore the interplay between the gut microbiota and Shigella infections. This investigation also involved 83 cases of Shigella infection patients and 336,396 control subjects. In the positive strand of our findings, we initially performed a preliminary analysis using the Inverse Variance Weighting (IVW) method. Subsequently, we undertook sensitivity analyses to assess the robustness of the results, addressing confounding factors’ influence. This involved employing the Leave-One-Out method and scrutinizing funnel plots to ensure the reliability of the MR analysis outcomes. Conclusively, a reverse MR analysis was carried out, employing the Wald ratio method due to the exposure of individual Single Nucleotide Polymorphisms (SNPs). This was undertaken to explore the plausible associations between Shigella infections and genetically predicted compositions of the gut microbiota.ResultsIn this study, we employed 2,818 SNPs associated with 211 species of gut microbiota as instrumental variables (IVs). Through IVW analysis, our positive MR findings revealed a significant negative correlation between the occurrence of Shigella infections and the phylum Tenericutes (OR: 0.18, 95% CI: 0.04–0.74, p = 0.02), class Mollicutes (OR: 0.18, 95% CI: 0.04–0.74, p = 0.02), genus Intestinimonas (OR: 0.16, 95% CI: 0.04–0.63, p = 0.01), genus Gordonibacter (OR: 0.39, 95% CI: 0.16–0.93, p = 0.03), and genus Butyrivibrio (OR: 0.44, 95% CI: 0.23–0.87, p = 0.02). Conversely, a positive correlation was observed between the occurrence of Shigella infections and genus Sutterella (OR: 10.16, 95% CI: 1.87–55.13, p = 0.01) and genus Alistipes (OR: 12.24, 95% CI: 1.71–87.34, p = 0.01). In sensitivity analyses, utilizing MR-Egger regression analysis and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) detection, all outcomes demonstrated robust stability. Simultaneously, in the reverse MR analysis, Shigella infections resulted in an upregulation of four bacterial genera and a downregulation of three bacterial genera.ConclusionIn summation, the MR analysis outcomes corroborate the presence of bidirectional causal relationships between the gut microbiota and Shigella infections. This study not only unveils novel perspectives for the prevention and treatment of Shigella infections but also furnishes fresh insights into the mechanistic underpinnings of how the gut microbiota contributes to the pathogenesis of Shigella infections. Consequently, the established dual causal association holds promise for advancing our understanding and addressing the complexities inherent in the interplay between the gut microbiota and Shigella infections, thereby paving the way for innovative therapeutic interventions and preventive strategies in the realm of Shigella-related diseases.

Abstract Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2.

Abstract Input-Output (IO) data describing supply-demand relationships between buyers and sellers for goods and services within an economy have been used not only in economics but also in scientific, environmental, and interdisciplinary research. However, most conventional IO data are highly aggregated, resulting in challenges for researchers and practitioners who face complex issues in large countries such as China, where firms within the same IO sector may have significant differences in technologies across subnational regions and different ownerships. This paper is the first attempt to compile China’s interprovincial IO (IPIO) tables with separate information for mainland China-, Hong Kong, Macau, Taiwan-, and foreign-owned firms inside each province/industry pair. To do this, we collect relevant Chinese economic census data, firm surveys, product level Custom trade statistics, and firm value-added tax invoices and consistently integrate them into a 42-sector, 31-province IO account covering 5 benchmark years between 1997–2017. This work provides a solid foundation for a diverse range of innovative IO-based research in which firm heterogeneity information about location and ownership matters.

Objectives: This study was performed to investigate the effect of non-pharmaceutical interventions on hand, foot, and mouth disease in Hubei Province China during the coronavirus disease 2019 pandemic. Methods: Data and samples were collected from the hand, foot, and mouth disease surveillance laboratory network in Hubei Province between 2018 and 2022. The samples were identified as Enterovirus A71, Coxsackievirus A6or Coxsackievirus A16 via real-time polymerase chain reaction. Representative Coxsackievirus A6 and Coxsackievirus A16 samples were sequenced and subjected to phylogenetic analyses. Results: A noticeable 3-fold reduction in the number of hand, foot, and mouth disease cases was observed from 2019 to 2020. The age and sex distributions of patients with hand, foot, and mouth disease were approximately the same from 2018 to 2022. The proportion of Coxsackievirus A6 accounted for 86 % in 2020 and 75 % in 2021 for hand, foot, and mouth disease compared with 48 % in 2018, 53 % in 2019, and 29 % in 2022. The proportions of Coxsackievirus A16 in 2020 and 2021 were 2 % and 17 %, respectively, showing a sharp decline in 2018 (37.8 %) and 2019 (35 %). In 2022, Coxsackievirus A16 was the dominant serotype (46 %). Only slight differences were found in the VP1 sequences across the different years. Conclusions: Our study confirmed that a series of non-pharmaceutical interventions during the coronavirus disease 2019 period reduced the transmission of enteroviruses and that long-term restrictions could significantly change the prevalence of enterovirus serotypes causing hand, foot, and mouth disease.

In this study, a total of 179 ticks infesting ruminant livestock, including 166 Haemaphysalis longicornis ticks and 13 Rhipicephalus microplus ticks were collected from Yingshan county of Hubei province, China in 2021–2022. PCR testing and sequence analysis revealed that the ticks infected with various species of pathogens including Rickettsia (R. japonica), Anaplasma (A. bovis, A. ovis, A. platys, and Ca. A. boleense), Ehrlichia (E. minasensis and Ehrlichia sp.), Theileria (T. orientalis and T. luwenshuni), and Babesia (B. bigemina). The infection rates of these pathogens were 0.56, 16.76, 7.26, 2.79 and 0.56%. respectively, while only 3 of 13 R. microplus ticks were detected to be infected wth Ehrlichia sp., A. bove., or T. luwenshuni. Our results revealed that a variety of tick-borne pathogens highly carried by these ticks, specially Ha. longicornis. Therefore, it is necessary to make effective control of the ticks and the tick-borne diseases in the County.

Abstract Air pollution is an important issue affecting sustainable development in China, and accurate air quality prediction has become an important means of air pollution control. At present, traditional methods, such as deterministic and statistical approaches, have large prediction errors and cannot provide effective information to prevent the negative effects of air pollution. Therefore, few existing methods could obtain accurate air pollutant time series predictions. To this end, a deep learning-based air pollutant prediction method, namely, the autocorrelation error-Informer (AE-Informer) model, is proposed in this study. The model implements the AE based on the Informer model. The AE-Informer model is used to predict the hourly concentrations of multiple air pollutants, including PM10, PM2.5, NO2, and O3. The experimental results show that the mean absolute error (MAE) and root mean square error (RMSE) values of AE-Informer in multivariate prediction are 3% less than those of the Informer model; thus, the prediction error is effectively reduced. In addition, a stacking ensemble model is proposed to supplement the missing air pollutant time series data. This study uses Henan Province in China as an example to test the validity of the proposed methodology.

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines.

A new sol-gel method that employs cation exchange from an aqueous metal ion solution with H+ ions of granulated alginic acid was developed for synthesizing high-purity Y2O3 nanoparticles. In this study, the cation exchange kinetics of H+~Y3+ in aqueous solution were analyzed using on-line pH technology and off-line inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. Pseudo 2nd-order models were utilized to evaluate the parameters of the kinetics, suggesting that the concentration of H+~Y3+ involved in the cation exchange reaction was 1:1.733. Further, a comprehensive understanding of the Y-ALG calcination process was developed using thermo-gravimetric analysis, along with results obtained from differential scanning calorimetry (TGA/DSC). A detailed analysis of the XRD Rietveld refinement plots revealed that the crystallite sizes of Y2O3 nanoparticles were about 4 nm (500 °C) and 15 nm (800 °C), respectively. Differential pulse voltammetry (DPV) was employed to investigate the electrochemical oxidation of catechol. The oxidation peak currents of catechol at Y2O3 (500 °C)/GCE and Y2O3 (800 °C)/GCE showed two stages linear function of concentration (2.0~20.0 × 10−6 mol/L, 20.0~60.0 × 10−6 mol/L). The results indicated that the detection limits were equal to 2.4 × 10−7 mol/L (Y2O3 (500 °C)/GCE) and 7.8 × 10−7 mol/L (Y2O3 (800 °C)/GCE). The study not only provided a method to synthesize metal oxide, but also proposed a promising on-line pH model to study cation exchange kinetics.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.

Global concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.529). So far, the infection features and immune escape ability of the Omicron variant have not been extensively studied. Here, we produced the Omicron pseudovirus and compared its entry, membrane fusion, and immune escape efficiency with the original strain and the dominating Delta variant. We found the Omicron variant showed slightly higher infectivity than the Delta variant and a similar ability to compete with the Delta variant in using Angiotensin-converting enzyme 2 (ACE2) in a BHK21-ACE2 cell line. However, the Omicron showed a significantly reduced fusogenicity than the original strain and the Delta variant in both BHK21-ACE2 and Vero-E6 cells. The neutralization assay testing the Wuhan convalescents’ sera one-year post-infection showed a more dramatic reduction (10.15 fold) of neutralization against the Omicron variant than the Delta variant (1.79 fold) compared with the original strain with D614G. Notably, immune-boosting through three vaccine shots significantly improved the convalescents’ immunity against the Omicron variants. Our results reveal a reduced fusogenicity and a striking immune escape ability of the Omicron variant, highlighting the importance of booster shots against the challenge of the SARS-CoV-2 antigenic drift.

Abstract Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.

Abstract Background MICAL1 is involved in the malignant processes of several types of cancer; however, the role of MICAL1 in pancreatic cancer (PC) has not been well-characterized. This study aimed to investigate the expression and function of MICAL1 in PC. Methods RT-qPCR and immunohistochemistry were used to detect MICAL1 expression in PC and adjacent nontumor tissues. Cell Counting Kit-8, EdU, clone formation, wound healing, and Transwell assays as well as animal models were used to investigate the effects of overexpression or inhibition of MICAL1 expression on the proliferation, invasion, and metastasis of PC cells. RNA-seq was used to explore the main pathway underlying the functions of MICAL1. Proteomics, mass spectrometry, and co-immunoprecipitation assays were used to investigate the interaction of proteins with MICAL1. Rescue experiments were conducted to validate these findings. Results Both MICAL1 mRNA and protein levels were upregulated in PC tissues compared with matched adjacent nontumor tissues. The expression level of MICAL1 was associated with the proliferative and metastatic status of PC. Repression of MICAL1 significantly inhibited PC cell growth, migration, and invasion in vitro and in vivo. RNA sequencing analysis indicated that MICAL1 was closely correlated with the WNT pathway. Overexpression of MICAL1 (1) promoted the phosphorylation of TBC1D1 at the Ser660 site, (2) facilitated the distribution of FZD7 on the cytomembrane, (3) inhibited the degradation of FZD7 in the lysosome, and (4) activated the WNT pathway. Conclusions MICAL1 was upregulated in PC and involved in stimulating the progression of PC cells by activating the WNT/β-catenin signaling pathway. Therefore, MICAL1 is a potential therapeutic target for PC.

Abstract Objective Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related mortality in adults. Syndecan-4 (SDC4) is involved in cancer pathogenesis. Therefore, this study aimed to explore the expression and clinical significance of SDC4 in PAAD. Methods Differentially expressed genes (DEGs) between PAAD and normal pancreas were screened from the GTEx and TCGA databases, and the correlationship between the DEGs and prognosis were analyzed. The prognostic value of the screened SDC4, SERPINE1, and SLC2A1 was evaluated using the Kaplan–Meier curve and SDC4 was subsequently selected as the better candidate. Also, SDC4 expression was analyzed in PAAD tissues, the other risk factors affecting postoperative survival were analyzed using Cox regression analysis, and SDC4-mediated pathways enrichment was identified by GSVA and GSEA. SDC4 expression in PAAD tissues and adjacent normal tissues of selected PAAD patients was detected by RT-qPCR and immunohistochemistry. The correlation between SDC4 and clinical features was evaluated by the χ2 test. Results SDC4 was highly expressed in PAAD tissues. Elevated SDC4 was correlated with reduced overall survival. SDC4 enrichment pathways included spliceosome function, proteasome activity, pentose phosphate pathway, base excision repair, mismatch repair, DNA replication, oxidative phosphorylation, mitotic spindle formation, epithelial-mesenchymal transition, and G2M checkpoints. SDC4 was elevated in PAAD tissues of PAAD patients compared with adjacent normal tissues. High SDC4 expression was related to metastatic differentiation, TNM stage, lymphatic metastasis, and lower 3-year survival rate. SDC4 was an independent risk factor affecting postoperative survival. Conclusion SDC4 was highly expressed in PAAD and was related to clinicopathological features and poor prognosis, which might be an important index for PAAD early diagnosis and prognosis.

Abstract Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.

An increasing number of studies have widely recognized that the gut mycobiota and bacteriophages are closely related to human health and disease, although little is known about the responses of fungi and phages that are induced by probiotics. In this study, based on published longitudinal cohorts, a meta-analysis of intestinal fungi and bacteriophages after probiotic consumption was performed. On the fungi, our results showed that probiotics had an effect size on the composition of intestinal fungi, and the strain specificity of probiotics were the most important influencing factors. In terms of phage, probiotics regulated the gut microbiome, which led to elevation and diminishment of multiple phages in the gut, although dramatic changes did not occur in the diversity and structure of intestinal bacteriophages after intervention with probiotics. Our study extended the understanding of the effects of probiotics on intestinal fungi and bacteriophages.

The COVID-19 pandemic, which was caused by SARS-CoV-2, has had a significant effect on global public health, economies, and societies worldwide. Serum antibody testing is a critical method for the diagnosis of COVID-19 and can complement RT-PCR in the diagnosis of COVID-19 patients; however, the performance of rapid antibody assays in the clinical setting has not been established. Rapid antibody assays were evaluated by investigating 296 COVID-19-positive individuals and 542 negative individuals confirmed by clinical diagnosis. The clinical diagnostic results were used as controls to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), kappa, and 95% confidence interval (CI) of the rapid tests. IgM-positivity had a sensitivity of 86.1% and specificity of 99.1%. IgG-positivity had a sensitivity of 86.5% and specificity of 98.7%. The sensitivity of combined IgM- and IgG-positivity in clinically confirmed patients was 73.1% in the early stage (1-7 days after symptom onset) and reached 99% 15 days after symptom onset. The concordance between rapid antibody-positive tests and clinical diagnosis-positivity had a kappa value of 0.93. In addition, the false-positive rate of IgM and IgG combined nucleic acid detection was 30% in the early stage. The combined use of IgM and IgG could serve as a more suitable alternative detection method for patients with COVID-19. The rapid antibody test can be considered as an excellent supplementary approach for detecting SARS-CoV-2 in clinical application.

Abstract Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.

Abstract Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.

Graphene is a two-dimensional material that can be folded into diverse and yet interesting nanostructures like macro-scale paper origami. Folding of graphene not only makes different morphological configurations but also modifies their mechanical and thermal properties. Inspired by paper origami, herein we studied systemically the effects of creases, where sp2 to sp3 bond transformation occurs, on the thermal properties of graphene origami using molecular dynamics (MD) simulations. Our MD simulation results show that tensile strain reduces (not increases) the interfacial thermal resistance owing to the presence of the crease. This unusual phenomenon is explained by the micro-heat flux migration and stress distribution. Our findings on the graphene origami enable the design of the next-generation thermal management devices and flexible electronics with tuneable properties.

The mechanical properties of calcium-silicate-hydrate (C-S-H) gels in cementitious materials are mainly realized by nanoindentation experiments. There is limited research on the dynamic response of the molecular structure of C-S-H under nanoindentation conditions. This study simulated the nanoindentation on the C-S-H gel samples by the molecular dynamics method considering the essential factors of modeling and loading process. The results demonstrate that the averaged elastic moduli we obtained had slight differences from those by experiments. In contrast to the experimental results, the gels showed bi-modulus and transverse isotropic with the material principal direction perpendicular to the C-S-H layers. The modulus in a direction increased with the loading speed, which indicates that C-S-H behaves viscous due to the water motion in the sample and the propagation of stress wave. The saturation of water influenced the moduli differently because more water in C-S-H will reduce the polymerization of silicon chains and then weaken the local stiffness. The conclusions provide a deeper understanding of the mechanism on the unique mechanical response of C-S-H gels.

Object detection in remote sensing images (RSIs) has become crucial in recent years. However, researchers often prioritize detecting small objects, neglecting medium- to large-sized ones. Moreover, detecting objects hidden in shadows is challenging. Additionally, most detectors have extensive parameters, leading to higher hardware costs. To address these issues, this paper proposes a multi-scale and high-precision lightweight object detector named MHLDet. Firstly, we integrated the SimAM attention mechanism into the backbone and constructed a new feature-extraction module called validity-neat feature extract (VNFE). This module captures more feature information while simultaneously reducing the number of parameters. Secondly, we propose an improved spatial pyramid pooling model, named SPPE, to integrate multi-scale feature information better, enhancing the model to detect multi-scale objects. Finally, this paper introduces the convolution aggregation crosslayer (CACL) into the network. This module can reduce the size of the feature map and enhance the ability to fuse context information, thereby obtaining a feature map with more semantic information. We performed evaluation experiments on both the SIMD dataset and the UCAS-AOD dataset. Compared to other methods, our approach achieved the highest detection accuracy. Furthermore, it reduced the number of parameters by 12.7% compared to YOLOv7-Tiny. The experimental results illustrated that our proposed method is more lightweight and exhibits superior detection accuracy compared to other lightweight models.

This article proposes a design method for a valve automatic assembly production line in response to the automation assembly requirements of electric valve products in space propulsion systems and the engineering problems of inaccurate loading force control and low valve measurement accuracy in existing process methods. This method can achieve five assembly processes during the assembly process of electric valves, including pre-tightening force control, valve-core stroke measurement, performance testing, and shell structure welding. The article introduces the design of platform components such as process execution, positioning, and transportation, as well as the design and operation process of workstations. By combining the design of a three-axis motion mechanism, a small turntable, and a robotic arm, the product can achieve professional, positioning, full process automation, and equipment miniaturization design across multiple workstations. Through the design of precise control of loading force and non-contact optical measurement method of moving structure, compared with the original method, the parameters affecting product performance are precisely controlled and the precision is improved. And the multivariable decoupling of valve product performance is realized by this method. Through application verification, this automatic assembly production line can significantly improve the assembly efficiency of electric valve products and solve difficult problems in product engineering.

Abstract Background Prodigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague. Methods The proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo. Results PG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models. Conclusion Taken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.

Objective(s): Endothelial dysfunction is a precursor of cardiovascular disease, and protecting endothelial cells from damage is a treatment strategy for atherosclerosis (AS). Curcumin, a natural polyphenolic compound, has been shown to protect endothelial cells from dysfunction. In the present study, we investigated whether curcumin could ameliorate high oxidized low-density lipoprotein (ox‐LDL)-induced endothelial lipotoxicity by inducing autophagy in human umbilical vein endothelial cells (HUVECs).Materials and Methods: HUVECs were treated with 50 μM high ox‐LDL alone or in combination with 5 μM curcumin for 24 hr. Cell viability and function were assessed by the cell counting kit-8 (CCK-8) assay, tube formation assay and cell migration experiments. Oil red O staining was used to detect lipid droplet accumulation in HUVECs. The change in reactive oxygen species (ROS) levels in HUVECs was measured with the probe DCFH-DA. Quantitative real-time PCR (qPCR) and Western blotting were used to evaluate the mRNA and protein levels of several inflammatory and autophagy-related factors.Results: Cell viability was restored, tube formation and migration ability were increased, and lipid accumulation, oxidative stress and inflammatory responses were decreased in the curcumin-treated group compared with the high ox‐LDL group. Furthermore, high ox‐LDL inhibited HUVEC autophagy, and this effect was reversed by curcumin. Moreover, curcumin regulated the expression of several key proteins involved in the AMPK/mTOR/p70S6K signaling pathway.Conclusion: Our findings suggest that curcumin is able to reduce endothelial lipotoxicity and modulate autophagy and that the AMPK/mTOR/p70S6K pathway might play a key role in these effects.

Abstract Air pollution is the result of comprehensive evolution of a dynamic and complex system composed of emission sources, topography, meteorology and other environmental factors. The establishment of spatiotemporal evolution model is of great significance for the study of air pollution mechanism, trend prediction, identification of pollution sources and pollution control. In this paper, the air pollution system is described based on cellular automata and restricted agents, and a Swarm Intelligence based Air Pollution SpatioTemporal Evolution (SI-APSTE) model is constructed. Then the spatiotemporal evolution analysis method of air pollution is studied. Taking Henan Province before and after COVID-19 pandemic as an example, the NO2 products of TROPOMI and OMI were analysed based on SI-APSTE model. The tropospheric NO2 Vertical Column Densities (VCDs) distribution characteristics of spatiotemporal variation of Henan province before COVID-19 pandemic were studied. Then the tropospheric NO2 VCDs of TROPOMI was used to study the pandemic period, month-on-month and year-on-year in 18 urban areas of Henan Province. The results show that SI-APSTE model can effectively analyse the spatiotemporal evolution of air pollution by using environmental big data and swarm intelligence, and also can establish a theoretical basis for pollution source identification and trend prediction.

Group A rotaviruses (RVAs) are major etiologic agents of gastroenteritis in infants and young children worldwide. To study the prevalence and genetic characteristics of RVAs, a hospital-based surveillance study was conducted in Wuhan, China from June 2019 through May 2022. The detection rates of RVAs were 19.40% (142/732) and 3.51% (8/228) in children and adults, respectively. G9P[8] was the predominant genotype, followed by G8P[8] and G3P[8]. G8P[8] emerged and was dominant in the 2021–2022 epidemic season. The genome constellation of six G8P[8] strains was assigned to G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that the VP7, VP4, VP2, VP3, NSP1, NSP2, NSP3, and NSP5 genes of these G8P[8] strains clustered closely with those of the G8P[8] strains in Asia and were distant from those of the P[8] and G2P[4] strains simultaneously detected in Wuhan. In contrast, the VP1, VP6, and NSP4 genes were closely related to the typical G2P[4] rotavirus, including those of G2P[4] strains simultaneously detected in Wuhan. The detection rate of RVAs decreased in the COVID-19 pandemic era. It was deduced that the G8P[8] rotaviruses that emerged in China may be reassortants, carrying the VP6, VP1, and NSP4 genes derived from the G2P[4] rotavirus in the backbone of the neighboring DS-1-like G8P[8] strains represented by CAU17L-103.

In this study, the spatiotemporal variations in CH4 concentrations in China from 2003 to 2021 are investigated, and their trends are forecasted over the next decade. Based on the seventh edition standard product retrieved by the atmospheric infrared detector (AIRS) at an altitude of 500 hPa, we verified monthly CH4 products using observational data provided by the World Data Center for Greenhouse Gases (WDCGG) from six ground stations in and around China. The correlation coefficients (R values) between the two data sets ranged from 0.68 to 0.92, signifying the ability of AIRS inversion data to represent temporal and spatial changes in surface CH4 concentrations. Additionally, China was classified into three regions (steps) based on terrain, and the changes in CH4 concentrations were assessed from three perspectives: spatial distribution, interannual variation, and seasonal variation. The results revealed that the CH4 concentration decreased with elevation along a topographic gradient, with high-value areas located in the first and second steps, corresponding to the eastern Qinghai–Tibet Plateau, northern Xinjiang Uygur Autonomous Region, and Inner Mongolia Autonomous Region. Over 19 years, the average increase in CH4 concentration has ranged from 65 to 175 ppb. In addition, the CH4 concentrations were higher during summer and autumn and lower during spring and winter. Finally, a SARIMA model was used to predict the near-surface CH4 concentration trend in China over the next ten years, which indicated a continued seasonal increase.

Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.

We propose a CNT-based concentric twin tube (CTT) as nanochannels for both water purification and ion separation at the nanoscale. In the model, a source reservoir dealing with the solution connects three containers via the CTT that has three subchannels for mass transfer. Before entering the three subchannels, the solution in the separating zone will form three layers (the aqua cations, water, and the aqua anions, respectively) by applying a charged capacitor with the two electrodes parallel to the flow direction of the solution. Under an electric field with moderate intensity, the three subchannels in the CTT have stable configurations for mass transfer. Since the water and the two types of aqua ions are collected by three different containers, the present model can realize both ion separation and water purification. The mass transfer in the subchannels will be sped up by an external pressure exerted on the solution in the source reservoir. The physical properties of the model, e.g., water purification speed, are analyzed with respect to the effects of the electric field, the size of CTT, and the concentration of solute, such as NaCl.

The formation of a bacterial biofilm on an infected wound can impede drug penetration and greatly thwart the healing process. Thus, it is essential to develop a wound dressing that can inhibit the growth of and remove biofilms, facilitating the healing of infected wounds. In this study, optimized eucalyptus essential oil nanoemulsions (EEO NEs) were prepared from eucalyptus essential oil, Tween 80, anhydrous ethanol, and water. Afterward, they were combined with a hydrogel matrix physically cross-linked with Carbomer 940 (CBM) and carboxymethyl chitosan (CMC) to prepare eucalyptus essential oil nanoemulsion hydrogels (CBM/CMC/EEO NE). The physical-chemical properties, in vitro bacterial inhibition, and biocompatibility of EEO NE and CBM/CMC/EEO NE were extensively investigated and the infected wound models were proposed to validate the in vivo therapeutic efficacy of CBM/CMC/EEO NE. The results showed that the average particle size of EEO NE was 15.34 ± 3.77 nm with PDI ˂ 0.2, the minimum inhibitory concentration (MIC) of EEO NE was 15 mg/mL, and the minimum bactericidal concentration (MBC) against S. aureus was 25 mg/mL. The inhibition and clearance of EEO NE against S. aureus biofilm at 2×MIC concentrations were 77.530 ± 7.292% and 60.700 ± 3.341%, respectively, demonstrating high anti-biofilm activity in vitro. CBM/CMC/EEO NE exhibited good rheology, water retention, porosity, water vapor permeability, and biocompatibility, meeting the requirements for trauma dressings. In vivo experiments revealed that CBM/CMC/EEO NE effectively promoted wound healing, reduced the bacterial load of wounds, and accelerated the recovery of epidermal and dermal tissue cells. Moreover, CBM/CMC/EEO NE significantly down-regulated the expression of two inflammatory factors, IL-6 and TNF-α, and up-regulated three growth-promoting factors, TGF-β1, VEGF, and EGF. Thus, the CBM/CMC/EEO NE hydrogel effectively treated wounds infected with S. aureus, enhancing the healing process. It is expected to be a new clinical alternative for healing infected wounds in the future.

Abstract Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined. The core set of genes relating to histone methylation (KMT2D, KMT2C, EZH2), histone acetylation (CREBBP, EP300), DNA methylation (TET2), and chromatin remodeling (ARID1A) were detected in the training cohort of 316 patients by whole-genome/exome sequencing (WGS/WES) and in the validation cohort of 303 patients with newly diagnosed DLBCL by targeted sequencing. Their correlation with peripheral blood immune cells and clinical outcomes were assessed. Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo. Among all 619 DLBCL patients, somatic mutations in KMT2D (19.5%) were most frequently observed, followed by mutations in ARID1A (8.7%), CREBBP (8.4%), KMT2C (8.2%), TET2 (7.8%), EP300 (6.8%), and EZH2 (2.9%). Among them, CREBBP/EP300 mutations were significantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios, as well as inferior progression-free and overall survival. In B-lymphoma cells, the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation, downregulated FBXW7 expression, activated the NOTCH pathway, and downstream CCL2/CSF1 expression, resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation. In B-lymphoma murine models, xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation, higher M2 macrophage recruitment, and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.

With the initial establishment of global earth observation system in various countries, more and more high-resolution remote sensing data of multisource, multitemporal, multiscale, and different types of satellites are obtained. It is urgent to explore the advanced basic theory of remote sensing information science, design high-performance generic key technologies of remote sensing information system and global positioning system, and study complex engineering system of remote sensing applications and geographic information system. In this article, the basic theory exploration, inversion technology research, and engineering application design and development of generic optical remote sensing product (ORSP) are systematically reviewed. We classify the ORSP scientifically, review the main algorithms and application scope of 16 kinds of generic ORSP, and expound the validation and quality evaluation methods of ORSP in engineering application. Furthermore, we analyze the current core problems and solutions, and prospects for the state-of-the-art research and the future development trend of generic ORSP. This will provide valuable reference for scientific research and construction of high-resolution earth observation system.

With the rapid development of high-resolution earth observation systems, the data processing, algorithm design, and system development of remote sensing spatial-temporal big data (RS-STBD) have gradually become the bottleneck problems in the application and development of earth observation system. The research on the model, algorithm, and system of RS-STBD processing involves complex scientific problems, technical bottlenecks, and inconstant requirements of engineering applications. This article summarizes the data type and processing theory model of RS-STBD, the high-performance algorithm design based on cloud service and intelligent computing, and the architecture design and engineering development methods of the complex remote sensing application system. Furthermore, the existing problems in the current research are analyzed, and the related solutions are given. Finally, the future development trend of scientific exploration, technical research, and application development of RS-STBD has prospected.

Abstract Nanotube can be used as a mass sensor. To design a mass sensor for evaluating a high-speed nanoparticle, in this study, we investigated the impact vibration of a cantilever nanobeam being transversally collided by a high-speed C60 at the beam's free end with an incident velocity of v In. The capped beam contains alternately two boron nitride zones and two carbon zones on its cross section. Hence, the relaxed beam has elliptic cross section. The vibration properties were demonstrated by molecular dynamics simulation results. Beat vibration of a slim beam can be found easily. The 1st and the 2nd order natural frequencies (f 1 and f 2) of the beam illustrate the vibration of beam along the short and the long axes of its elliptic cross section, respectively. f 2 decreases with increasing temperature. A minimal value of v In leads to the local buckling of the beam, and a different minimal v In leading to damage of the beam. For the same system at a specified temperature, f 2 varies with v In. When the beam bends almost uniformly, f 2 decreases linearly with v In. If v In becomes higher, the beam has a cross section which buckles locally, and the buckling position varies during vibration. If v In approaches the damage velocity, a fixed contraflexture point may appear on the beam due to its strong buckling. Above the damage velocity, f 2 decreases sharply. These results have a potential application in design of a mass sensor.

ABSTRACT As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release. IMPORTANCE Enveloped virus particles are released from the membranes of host cells, and viral membrane proteins (M) are critical for this process. A better understanding of the molecular mechanisms of SARS-CoV-2 assembly and budding is critical for the development of antiviral therapies. Envelope protein (E) and M of SARS-CoV-2 form complexes to mediate viral assembly and budding. RNF5 was identified to play a role as the E3 ligase, and POH1 was demonstrated to function as the deubiquitinating enzyme of SARS-CoV-2 M. The two components collectively regulate the interaction of M with E to promote viral assembly and budding. Ubiquitinated M uses autophagosomes for viral release. Our findings provide insights into the mechanisms of SARS-CoV-2 assembly and budding, demonstrating the importance of ubiquitination modification and autophagy in viral replication.

The chitooligosaccharide (COS) and chlorella polysaccharide (CPS) have been used as feed supplements in the poultry industry for improving growth performance and immunity. However, the benefits of these prebiotics on the gut health of chickens when used in early nutrition are unknown. This study evaluated the effects of in ovo feeding of COS and CPS on the cecal microbiome, metabolic pathways, and fermentation metabolites of chickens. A total of 240 fertile eggs were divided into 6 groups (n = 4; 10 eggs/replicate): 1) no-injection control, 2) normal saline control, 3) COS 5 mg, 4) COS 20 mg, 5) CPS 5 mg, and 6) CPS 20 mg injection. On day 12.5 of egg incubation, test substrate was injected into the amniotic sac of eggs in respective treatments. The hatched chicks were raised for 21 D under standard husbandry practices. On day 3 and 21, cecal digesta were collected to determine microbiota by shotgun metagenomic sequencing and short-chain fatty acids by gas chromatography. The cecal microbial composition was not different (P > 0.05) among the treatment groups on day 3 but was different (P

Cancer stem cells are the main reason for drug resistance and tumor relapse, and screening the targets for cancer stem cells is essential for tumor therapy. Here, we studied the role and regulatory mechanism of a G protein-coupled receptor named as G protein-coupled receptor 87 (GPR87) in the expansion of pancreatic ductal adenocarcinoma (PDA) stem cells. We found that GPR87 was an independent prognostic factor for PDA patients: patients with high GPR87 had a poor outcome. GPR87 significantly promoted the sphere formation ability, increased side population (SP) cell number, increased the expression of PDA stem cell markers, and increased the tumor initiation ability, suggesting that GPR87 promotes the expansion of PDA stem cells. Mechanism analysis suggested that signal transducer and activator of transcription 3 (STAT3) directly bound to the promoter of GPR87 to increase GPR87 expression; inversely, GPR87 also activated STAT3. Further analysis suggested that GPR87 activated Janus kinase 2 (JAK2), which can activate STAT3, inhibiting JAK2 activation in GPR87-overexpressing PDA cells, which significantly inhibited the expansion of PDA stem cells; these findings suggested that GPR87, JAK2, and STAT3 formed a positive feedback loop increasing PDA stem cell population. In PDA specimens, GPR87 expression is positively correlated with the phosphorylation level of STAT3 and JAK2, confirming GPR87 promoted PDA stem cell expansion through activating JAK2/STAT3. In summary, we found that GPR87, together with JAK2 and STAT3, formed a positive feedback loop to promote the expansion of PDA stem cells.

Abstract Background Bacterial gas vesicles, composed of two major gas vesicle proteins and filled with gas, are a unique class of intracellular bubble-like nanostructures. They provide buoyancy for cells, and thus play an essential role in the growth and survival of aquatic and soil microbes. Moreover, the gas vesicle could be applied to multimodal and noninvasive biological imaging as a potential nanoscale contrast agent. To date, cylinder-shaped gas vesicles have been found in several strains of cyanobacteria. However, whether the functional gas vesicles could be produced in the model filamentous cyanobacteria Anabaena sp. PCC 7120 remains controversial. Results In this study, we found that an intact gvp gene cluster indeed exists in the model filamentous cyanobacteria Anabaena sp. PCC 7120. Real-time PCR assays showed that the gvpA gene is constitutively transcribed in vivo, and its expression level is upregulated at low light intensity and/or high growth temperature. Functional expression of this intact gvp gene cluster enables the recombinant Escherichia coli to gain the capability of floatation in the liquid medium, thanks to the assembly of irregular gas vesicles. Furthermore, crystal structure of GvpF in combination with enzymatic activity assays of GvpN suggested that these two auxiliary proteins of gas vesicle are structurally and enzymatically conserved, respectively. Conclusions Our findings show that the laboratory strain of model filamentous cyanobacteria Anabaena sp. PCC 7120 possesses an intact but partially degenerated gas vesicle gene cluster, indicating that the natural isolate might be able to produce gas vesicles under some given environmental stimuli for better floatation.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has resulted in a global pandemic.Methodology: We used a two-step polymerase chain reaction to detect the ACE genotype and ELISA kits to detect the cytokine factor. We also used proteomics to identify the immune pathway related to the ACE protein expression.Result: In this study, we found that the angiotensin-converting enzyme (ACE) deletion polymorphism was associated with the susceptibility to COVID-19 in a risk-dependent manner among the Chinese population. D/D genotype distributions were higher in the COVID-19 disease group than in the control group (D/D odds ratio is 3.87 for mild (p value < 0.0001), 2.59 for moderate (p value = 0.0002), and 4.05 for severe symptoms (p value < 0.0001), logic regression analysis. Moreover, genotype-specific cytokine storms and immune responses were found enriched in patients with the ACE deletion polymorphism, suggesting the contribution to the susceptibility to COVID-19. Finally, we identified the immune pathway such as the complement system related to the ACE protein expression of patients by lung and plasma proteomics.Conclusion: Our results demonstrated that it is very important to consider gene polymorphisms in the population to discover a host-based COVID-19 vaccine and drug design for preventive and precision medicine.