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Zhang et al. show that the circadian gene coupling between night feeding and day detoxification is regulated through the binding of circadian elements to E-boxes in Spodoptera litura, one of the most difficult Asian agricultural pests to control. Exposure of these larvae to a pesticide affects them more at night than during the day, suggesting the need for time-of-day considerations for pesticide application.

The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.

The snow temperature above the ice sheet is one of the basic characteristic parameters of the ice sheet, which plays an important role in the study of the global climate. Because infrared and microwaves with different frequencies have different penetration depths in snow, it is possible to retrieve the snow temperature profiles by combining microwave and infrared brightness temperatures. This paper proposes a conjoint inversion algorithm to retrieve snow temperature profiles by combining multi-frequency microwave brightness temperature (BT) with infrared BT, in which different weight functions of microwave BT at different frequencies are adopted, and the atmosphere influence has also been corrected. The snow temperature profile data are retrieved based on AMSR2 microwave BT data and MODIS infrared BT data in 2017 and 2018, which are evaluated by comparing with the measured snow temperature at Dome-C station. The results confirm that the inverted snow temperature profiles are consistent with the field observation data from the Dome-C station. Multi-frequency microwave brightness temperature can be used to invert the snow temperature profiles; however, the inverted snow surface temperature is more accurate by combining the infrared BT with the microwave BT in the conjoint inversion algorithm.

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18–55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 107 EID50/ dose and 1 × 107.7 EID50/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/106 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/106 PBMC (day 42) from 2.5 SFU/106 PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.

The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years.

Although nitrogen (N) deficiency greatly affects N absorption and metabolism in barley, the global transcriptomic changes in morphological and physiological adaptation to altered N availability remains largely unclear. We conducted a comparative transcriptome analysis of roots in A9-29 (low N tolerant line of barley) and Hua 30 (low N-sensitive variety of barley) under low N conditions to elucidate the responses and the underlying molecular mechanism. The results demonstrated that the root architecture was strongly influenced and that the root morphological indexes (total root length, total root area surface, and root volume) were remarkably promoted in A9-29 compared to Hua30 under low N stress. The transcriptome analysis of roots identified 1779 upregulated differentially expressed genes (DEGs) and 1487 downregulated DEGs specifically expressed in A9-29 under low N stress. Specific DEGs in A9-29 were largely enriched in energy metabolism, lipid metabolism, and the metabolism of other amino acids. In addition, transcription factor genes ERFs and IAA-related genes were specifically expressed in A9-29. To conclude, this study could provide a foundation for improving low N tolerance in barley.

Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

The Coronavirus Disease 2019 (COVID-19) pandemic is unlikely to abate until sufficient herd immunity is built up by either natural infection or vaccination. We previously identified ten linear immunodominant sites on the SARS-CoV-2 spike protein of which four are located within the RBD. Therefore, we designed two linkerimmunodominant site (LIS) vaccine candidates which are composed of four immunodominant sites within the RBD (RBD-ID) or all the 10 immunodominant sites within the whole spike (S-ID). They were administered by subcutaneous injection and were tested for immunogenicity and in vivo protective efficacy in a hamster model for COVID-19. We showed that the S-ID vaccine induced significantly better neutralizing antibody response than RBD-ID and alum control. As expected, hamsters vaccinated by S-ID had significantly less body weight loss, lung viral load, and histopathological changes of pneumonia. The S-ID has the potential to be an effective vaccine for protection against COVID-19.

BackgroundNumerous studies validated frequent glucose dysfunction in patients with acute pancreatitis (AP). However, the prevalence of new-onset diabetes in individuals after a first episode of AP varies widely among previous studies. This study aims to determine the incidence of post-acute pancreatitis diabetes mellitus (PPDM-A) in Chinese people and further identify potential risk factors that influence diabetes development in patients with AP.MethodsThis was a multi-center retrospective cohort study including 6009 inpatients with a first attack of AP. A total of 1804 patients with AP without known endocrine pancreatic disorders or other pancreatic exocrine diseases were eligible for analysis. Data was collected from medical records by hospital information system and telephone follow-ups after discharge. The multiple logistic regression analysis was established to evaluate the potential influencing factors of PPDM-A.ResultsThe prevalence of newly diagnosed diabetes after a first episode of AP in China was 6.2%. Data showed that patients who developed PPDM-A were more likely to be younger (X2 = 6.329, P = 0.012), experienced longer hospital stays (X2 = 6.949, P = 0.008) and had a higher frequency of overweight or obesity (X2 = 11.559, P = 0.003) compared to those with normal glycemia. The frequency of stress hyperglycemia on admission (X2 = 53.815, P < 0.001), hyperlipidemia (X2 = 33.594, P < 0.001) and non-alcoholic fatty liver disease (NAFLD) (X2 = 36.335, P < 0.001) were significantly higher among individuals with PPDM-A compared with control group. Also, patients with PPDM-A were more likely to be hyperlipidemic AP (X2 = 16.304, P = 0.001) and show a higher degree of severity (X2 = 7.834, P = 0.020) and recurrence rate (X2 = 26.908, P < 0.001) of AP compared to those without diabetes. In addition, multiple logistic regression analysis indicated that stress hyperglycemia, hyperlipidemia, NAFLD and repeated attacks of AP were the independent influence factors for developing PPDM-A.ConclusionOur study first demonstrated the prevalence of secondary diabetes in Chinese patients after AP. The disorder of glucose metabolism in individuals with AP should be regularly evaluated in clinical practice. Further studies are needed to verify the relationship between liver and pancreas in keeping glucose homeostasis under AP condition.

Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein–protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA–mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level.

Epstein Barr virus (EBV) can affect 90% of the human population. It can invade B lymphocytes, T lymphocytes and natural killer cells of the host and remain in the host for life. The long latency and reactivation of EBV can cause malignant transformation, leading to various lymphoproliferative diseases (LPDs), including EBV-related B-cell lymphoproliferative diseases (EBV-B-LPDs) (for example, Burkitt lymphoma (BL), classic Hodgkin’s lymphoma (cHL), and posttransplantation and HIV-related lymphoproliferative diseases) and EBV-related T-cell lymphoproliferative diseases (EBV-T/NK-LPDs) (for example, extranodal nasal type natural killer/T-cell lymphoma (ENKTCL), aggressive NK cell leukaemia (ANKL), and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). EBV-LPDs are heterogeneous with different clinical features and prognoses. The treatment of EBV-LPDs is usually similar to that of EBV-negative lymphoma with the same histology and can include chemotherapy, radiotherapy, and hematopoietic stem cell transplant (HSCT). However, problems such as serious toxicity and drug resistance worsen the survival prognosis of patients. EBV expresses a variety of viral and lytic proteins that regulate cell cycle and death processes and promote the survival of tumour cells. Based on these characteristics, a series of treatment strategies for EBV in related malignant tumours have been developed, such as monoclonal antibodies, immune checkpoint inhibitors, cytotoxic T lymphocytes (CTLs) and epigenetic therapy. These new individualized therapies can produce highly specific killing effects on tumour cells, and nontumour cells can be protected from toxicity. This paper will focus on the latest progress in the treatment of EBV-LPDs based on pathological mechanisms.

ObjectsIt has been recognized the nexus between trisomy 8 and auto-inflammatory features in myelodysplasia syndrome (MDS). Recent research about VEXAS syndrome proved clonal hematopoiesis could interfere with innate immune system far before occurrence of hematological malignancies. We reported a case series of clonal cytopenia with auto-inflammatory features in trisomy 8 patients.MethodsA total of six patients with isolated trisomy 8 excluded from MDS was retrospectively collected from the Department of Rheumatology, Renji Hospital, Shanghai. The clinical presentations and treatment outcomes were presented.ResultsWe report patients with trisomy 8 shared the auto-inflammatory features of recurrent fever, arthralgia, gastrointestinal involvement, and elevated inflammatory markers, especially hyperferritinemia, in addition to hematological findings such as macrocytic anemia and cytopenia of other lineages but without myelodysplasia. The symptoms of this disorder responded to the treatment of glucocorticoids but difficult to taper. JAK inhibitors were introduced to four patients with enhanced response along with glucocorticoids sparing effect and good tolerance.ConclusionClonal cytopenia harboring trisomy 8 presenting with auto-inflammatory features was identified. JAK inhibitor may be a promising anti-inflammatory option.

Species delimitation by traditional morphological methods is challenging in cephalopods due to their flexible bodies, changeable pigment traits, and sometimes high morphological homoplasy. Molecular information provides important assistance for taxonomic decision. In this study, we applied three species delimitation methods on 132 cephalopods from 7 families along Chinese waters, and we found anunderestimated species diversity in these taxa. A maximum of 56 molecular operational taxonomic units was detected, and possible cryptic diversities were revealed in Loliolus beka, Uroteuthis edulis, Octopus minor, Amphioctopus fangsiao, and Hapalochlaena lunulate. This study provides molecular evidence for the hidden species diversity along Chinese waters, and it provides insight into further taxonomic research on these morphologically variable taxa.

Summary: Background: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. Methods: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. Findings: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC50 and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ+ CD4+ T or IFN-γ+ CD8+ T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC50 titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%,

Abstract Background Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) and Paeonia lactiflora Pall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair. Methods A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets. Results The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect. Conclusion This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.

Abstract Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS.

Abstract Background Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods Serum samples of 30 healthy controls, 14 DM patients without ILD and 40 DM patients with ILD were collected. Serum S100A8/A9 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and levels of interleukins were measured by cytometric beads array (CBA). Then we performed multivariate logistic regression analysis to determine factors independently associated with ILD development. Results Serum IL-4, IL-6 and S100A8/A9 levels were significantly higher in DM patients with ILD than those in healthy controls (p = 0.0013, 0.0017 and

Microstructures are critical for designing composite materials with admirable properties required by various applications. However, desired inclusion arrangements are pre-required and have to be reached by appropriate processing as well as quantitative evaluation. Up to date, visual characterization like transmission electron microscope is still the “golden rule” for measuring inclusion arrangement, together with qualitative descriptions in most studies. In order to establish structure-property relationship, optimize processing parameters and even predict composite performances, quantitative evaluation of inclusion arrangement becomes a must. This review focuses on the numerous developed mainstream quantitative approaches and their recent advances. Methods, including ASTM index (American Society of Testing Materials), Morishita’s index, quadrat method, linear intercept distance, free-path spacing, nearest neighbor distance, inter-particle distance, free-space length, functional analysis, Delaunay triangulation and Dirichlet tessellation, are classified into three categories: methods based on inclusion features, methods based on inclusion position and methods based on inclusion position and inter-distance, which are introduced in the manuscript. Definition, advantages, updated progress and recent application examples of specific method are included. The differences between each methods and their limitations are summarized.

Abstract Background Reducing the dependence of crop production on chemical fertilizer with its associated costs, carbon footprint and other environmental problems is a challenge for agriculture. New solutions are required to solve this problem, and crop breeding for high nitrogen use efficiency or tolerance of low nitrogen availability has been widely considered to be a promising approach. However, the molecular mechanisms of high nitrogen use efficiency or low-nitrogen tolerance in crop plants are still to be elucidated, including the role of long non-coding RNAs (lncRNAs). Results In this study, we identified 498 lncRNAs in barley (Hordeum vulgare) landrace B968 (Liuzhutouzidamai), of which 487 were novel, and characterised 56 that were responsive to low-nitrogen stress. For functional analysis of differentially-expressed lncRNAs, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of co-expressed and co-located protein-coding genes were analyzed, and interactions with annotated co-expressed protein coding genes or micro RNAs (miRNAs) were further predicted. Target mimicry prediction between differentially-expressed lncRNAs and miRNAs identified 40 putative target mimics of lncRNAs and 58 target miRNAs. Six differentially-expressed lncRNAs were further validated by qPCR, and one in particular showed consistent differential expression using both techniques. Expression levels of most of the lncRNAs were found to be very low, and this may be the reason for the apparent inconsistency between RNA-seq and qPCR data. Conclusions The analysis of lncRNAs that are differentially-expressed under low-nitrogen stress, as well as their co-expressed or co-located protein coding genes and target mimics, could elucidate complex and hitherto uncharacterised mechanisms involved in the adaptation to low-nitrogen stress in barley and other crop plants.

Memristor devices based on ferroelectric tunnel junctions are promising, but suffer from quite slow switching times. Here, the authors report on ultrafast switching times at and above room temperature of 600ps in Ag/BaTiO3/Nb:SrTiO3 based ferroelectric tunnel junctions.

Abstract Background The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. Method From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. Results At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28–0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). Conclusion For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. Trial Registration NCT 01441752 . Registered 14 July, 2011.

Checkpoint immunotherapy is a major breakthrough for cancer treatment, yet its efficacy is often limited against many types of malignancies, including malignant mesothelioma. Considering that the immunotherapeutic efficacy depends on immunosurveillance, we sought to develop an active immunization method to break immune tolerance to tumor self-antigen. Here, we demonstrated that TWIST1, the basic helix-loop-helix transcription factor, was associated with human mesothelioma tumorigenesis and required for the invasion and metastasis of mesothelioma in the immune-competent murine AB1 model. When conventional TWIST1 vaccines were not effective in vivo, programmed cell death protein 1 (PD1)-based vaccination provided prophylactic control by inducing long-lasting TWIST1-specific T cell responses against both subcutaneous and metastatic mesothelioma lethal challenges. Furthermore, while CTLA-4 blockade alone did not show any immunotherapeutic efficacy against established mesothelioma, its combination with PD1-based vaccination resulted in 60% complete remission. Mechanistically, these functional T cells recognized a novel highly conserved immunodominant TWIST1 epitope, exhibited cytotoxic activity and long-term memory, and led to durable tumor regression and survival benefit against established AB1 mesothelioma and 4T1 breast cancer. We concluded that PD1-based vaccination controls mesothelioma by breaking immune tolerance to the tumor self-antigen TWIST1. Our results warrant clinical development of the PD1-based vaccination to enhance immunotherapy against a wide range of TWIST1-expressing tumors. Keywords: DNA vaccine, TWIST1 antigen, mesothelioma, PD1, soluble PD1-based vaccination, CTLA-4, cytotoxic T lymphocytes, immune checkpoint blockade

ABSTRACTCoronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.

ABSTRACTThe emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.

As data volume grows extensively, data profiling helps to extract metadata of large-scale data. However, one kind of metadata, order statistics, is difficult to be computed because they are not mergeable or incremental. Thus, the limitation of time and memory space does not support their computation on large-scale data. In this paper, we focus on an order statistic, quantiles, and present a comprehensive analysis of studies on approximate quantile computation. Both deterministic algorithms and randomized algorithms that compute approximate quantiles over streaming models or distributed models are covered. Then, multiple techniques for improving the efficiency and performance of approximate quantile algorithms in various scenarios, such as skewed data and high-speed data streams, are presented. Finally, we conclude with coverage of existing packages in different languages and with a brief discussion of the future direction in this area.

Due to its advantages of small size and light weight, multi-pulse rectifier has a broad application prospect in the field of aviation. The 18-pulse rectifier is more popular in practical engineering application because of its better rectifier characteristics than 12-pulse, its simpler structure process and easier to realize than 24-pulse. The theoretical research and engineering application of the 18-pulse rectifier have achieved some success. However, whether the reliability of the system can be satisfied has always been one of the key problems to be solved in practical engineering. The aim of this work is to study the reliability modeling and prediction of the 18-pulse rectifier power supply. Its reliability block diagram and mathematical model are established. According to US Military handbook MIL-HDBK-217F, the most authoritative and widely used in the world, the two most commonly used methods for reliability prediction are parts count method and part stress analysis method. The reliability data are estimated by these two methods. It is concluded that the value of mean time between failures in airborne environment is 23326 h, which meets the requirement of 1.5 times of 15000 h. According to the reliability data, the failure mode and effect analysis of its weak links are carried out, and the improvement measures are proposed. This will promote and guide the reliability growth and engineering popularization of the 18-pulse rectifier power supply. At the same time, the reliability of the actual project can be extended to other related engineering applications to ensure the reliable operation of the system.

Variation modes of avian wings offer large-scale morphing aircraft an effective approach for solving problems such as the mass center shift in longitudinal trim and control system design during the morphing process. In this paper, a numerical method is established for fully understanding the influence of combined morphing on roll efficiency of a biomimetic wing unmanned aerial vehicle (UAV) from the perspective of aerodynamic change, system convergence time and aerodynamic energy consumption. Analysis and simulation results show that the biomimetic wing provides effective measures to improve the mission execution efficiency of UAV. System oscillation can obviously be reduced with asymmetric sweep angle change as the supervisory control surface for pure roll maneuver, and actuators require higher output power than that with the single deflection of the flexible trailing edge (Flex-TE). In addition, for aircraft design, a larger mass ratio of the inner wing is beneficial to enhance system stability. Energy consumption of wing and Flex-TE show laws of first increasing and then decreasing along the spanwise direction during the morphing process. For actuators of the Flex-TE, the output power of units 1 to 15 should higher than other spanwise units. For the sweep angle generalized control surface, the maximum value of energy consumption per unit time is located near the 20-th spanwise unit.

Summary: Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. Interpretation: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. Funding: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.

Objective To identify key genes in hepatitis C virus (HCV)-induced cirrhosis and to predict effective drugs for its treatment. Methods Three datasets were used to screen for differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in HCV-induced cirrhosis. DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the clusterProfiler R package. Their respective protein–protein interaction (PPI) networks were constructed using Cytoscape. Cross analysis of DEGs and DMGs was performed to identify the genetic landscape of HCV-induced cirrhosis, and five genes were validated by receiver operating characteristic curve analysis. Molecular autodocking between ISG15 and natural products was performed using AutoDock Tool 1.5.6. Results A total of 357 DEGs and 8,830 DMGs were identified. DEG functional analysis identified several pathways involved in the pathogenesis of HCV-induced cirrhosis. Cross analysis of DEGs and DMGs identified 212 genes, and PPI network analysis identified 25 hub genes. Finally, five genes including ISG15 were identified and confirmed in dataset GSE36411. Artesunate and betulinic acid were shown to have a strong binding affinity to ISG15. Conclusion Our study provides novel insights into the mechanisms of HCV-induced cirrhosis which could lead to the identification of new therapeutics.

In order to improve the spatial resolution of a one-dimensional aperture synthesis (1-D AS) radiometer without increasing the size of the antenna array, the method of visibility extension (VE) is proposed in this article. In the VE method, prior information about the visibility distribution of various scenes is learnt by a residual convolutional neural network (ResCNN). Specifically, the relationship between the distribution of low-frequency visibility and that of high-frequency visibility is learnt. Then, the ResCNN is used to estimate the high-frequency visibility samples from the low-frequency visibility samples obtained by the AS system. Furthermore, the low- and high-frequency visibility samples are combined to reconstruct the brightness temperature image of the scene, to enhance the spatial resolution of AS. The simulation and experiment both demonstrate that the VE method can enhance the spatial resolution of 1-D AS.

Vision-based modal analysis has gained popularity in the field of structural health monitoring due to significant advancements in optics and computer science. For long term monitoring, the structures are subjected to ambient excitation, so that their vibration amplitudes are quite small. Hence, although natural frequencies can be usually identified from the extracted displacements by vision-based techniques, it is still difficult to evaluate the corresponding mode shapes accurately due to limited resolution. In this study, a novel signal reconstruction algorithm is proposed to reconstruct the dynamic response extracted by the vision-based approach to identify the mode shapes of structures with low amplitude vibration due to environmental excitation. The experimental test of a cantilever beam shows that even if the vibration amplitude is as low as 0.01 mm, the first two mode shapes can be accurately identified if the proposed signal reconstruction algorithm is implemented, while without the proposed algorithm, they can only be identified when the vibration amplitude is at least 0.06 mm. The proposed algorithm can also perform well with various camera settings, indicating great potential to be used for vision-based structural health monitoring.

According to the structures traced by ^13 CO spectral lines within ^12 CO molecular clouds (MCs), we investigate the contributions of their internal gas motions and relative motions to the total velocity dispersions of ^12 CO MCs. Our samples of 2851 ^12 CO MCs harbor a total of 9556 individual ^13 CO structures, among which 1848 MCs (∼65%) have one individual ^13 CO structure and the other 1003 MCs (∼35%) have multiple ^13 CO structures. We find that the contribution of the relative motion between ^13 CO structures ( ${\sigma }_{{}^{13}\mathrm{CO},\mathrm{re}}$ ) is larger than that from their internal gas motion ( ${\sigma }_{{}^{13}\mathrm{CO},\mathrm{in}}$ ) in ∼62% of 1003 MCs in the “Multiple” regime. In addition, we find that ${\sigma }_{{}^{13}\mathrm{CO},\mathrm{re}}$ tends to increase with the total velocity dispersion ( ${\sigma }_{{}^{12}\mathrm{CO},\mathrm{tot}}$ ) in our samples, especially for MCs with multiple ^13 CO structures. This result provides a manifestation of macroturbulence within MCs, which gradually becomes the dominant way of storing kinetic energy along with the development of MC scales.

We universally search for evidence of kinematic and spatial correlation of supernova remnant (SNR) and molecular cloud (MC) associations for nearly all SNRs in the coverage of the Milky Way Imaging Scroll Painting CO survey, i.e., 149 SNRs, 170 SNR candidates, and 18 pure pulsar wind nebulae in 1° < l < 230° and −5.°5 < b < 5.°5. Based on high-quality and unbiased ^12 CO/ ^13 CO/C ^18 O ( J = 1–0) survey data, we apply automatic algorithms to identify broad lines and spatial correlations for molecular gas in each SNR region. The 91% of SNR–MC associations detected previously are identified in this paper by CO line emission. Overall, there could be as high as 80% of SNRs associated with MCs. The proportion of SNRs associated with MCs is high within the Galactic longitude less than ∼50°. Kinematic distances of all SNRs that are associated with MCs are estimated based on systemic velocities of associated MCs. The radii of SNRs associated with MCs follow a lognormal distribution, which peaks at ∼8.1 pc. The progenitor initial mass of these SNRs follows a power-law distribution with an index of ∼−2.3 that is consistent with the Salpeter index of −2.35. We find that SNR–MC associations are mainly distributed in a thin disk along the Galactic plane, while a small number are distributed in a thick disk. With the height of these SNRs from the Galactic plane below ∼45 pc, the distribution of the average radius relative to the height of them is roughly flat, and the average radius increases with the height when above ∼45 pc.

We have used the IRAM 30 m telescope to map some targets with HCO ^+ (1–0) and H ^13 CO ^+ (1–0) lines in order to search for evidence of gas infall in clumps. In this paper, we report the mapping results for 13 targets. All of these targets show HCO ^+ emissions, while H ^13 CO ^+ emissions are observed in 10 of them. The HCO ^+ integrated intensity maps of 10 targets show clear clumpy structures, and nine targets show clumpy structures in the H ^13 CO ^+ maps. Using the RADEX radiative transfer code, we estimate the column density of H ^13 CO ^+ , and we determine the abundance ratio [H ^13 CO ^+ ]/[H _2 ] to be approximately 10 ^−12 –10 ^−10 . Based on the asymmetry of the HCO ^+ line profiles, we identify 11 targets that show blue profiles, while six clumps have evidence of global infall. We use the RATRAN and two-layer models to fit the HCO ^+ line profiles of these infall sources, and analyze their spatial distribution of the infall velocity. The average infall velocities estimated by these two models are 0.24–1.85 km s ^−1 and 0.28–1.45 km s ^−1 , respectively. The mass infall rate ranges from approximately 10 ^−5 to 10 ^−2 M _⊙ yr ^−1 , which suggests that intermediate- or high-mass stars may be forming in the target regions.

We present the results of an unbiased ^12 CO/ ^13 CO/C ^18 O ( J = 1–0) survey in a portion of the third Galactic quadrant (TGQ): 219.°75 ≤ l ≤ 229.°75 and −5.°25 ≤ b ≤ 5.°25. The high-resolution and high-sensitivity data sets help to unravel the distributions and physical properties of the molecular clouds (MCs) in the mapped area. In the LSR velocity range from ∼−1 to ∼85 km s ^−1 , the molecular material successfully traces the Local, Perseus, and Outer arms. In the TGQ, the Outer arm appears to be more prominent than that in the second Galactic quadrant (SGQ), but the Perseus arm is not as conspicuous as that in the SGQ. A total of 1,502 ^12 CO, 570 ^13 CO, and 53 C ^18 O molecular structures are identified, spanning over ∼2 and ∼6 orders of magnitude in size and mass, respectively. Tight mass–radius correlations and virial parameter–mass anticorrelations are observable. Yet, it seems that no clear correlations between velocity dispersion and effective radius can be found over the full dynamic range. The vertical distribution of the MCs renders evident pictures of the Galactic warp and flare.

Gravitational waves emitted from stellar binary black hole (sBBH) mergers can be gravitationally lensed by intervening galaxies and detected by future ground-based detectors. A great amount of effort has been put into the estimation of the detection rate of lensed sBBH originating from the evolution of massive binary stars (EMBS channel). However, sBBHs produced by the dynamical interaction in dense clusters (dynamical channel) may also be dominant in our universe and their intrinsic distribution of physical properties can be significantly different from those produced by massive stars, especially mass and redshift distribution. In this paper, we investigate the event rate of lensed sBBHs produced via the dynamical channel by Monte Carlo simulations and the number is ${16}_{-12}^{+4.7}$ yr ^−1 for the Einstein telescope and ${24}_{-17}^{+6.8}$ yr ^−1 for Cosmic Explorer, of which the median is about ∼2 times the rate of sBBHs originating from the EMBS channel (calibrated by the local merger rate density estimated for the dynamical and the EMBS channel, i.e., $\sim {14}_{-10}^{+4.0}$ and ${19}_{-3.0}^{+42}\,\,{\mathrm{Gpc}}^{-3}\,{\mathrm{yr}}^{-1}$ , respectively). Therefore, one may constrain the fraction of both the EMBS and dynamical channels through the comparison of the predicted and observed number of lensed sBBH events statistically.

A comprehensive understanding of molecular clumps is essential for investigating star formation. We present an algorithm for molecular clump detection, called FacetClumps. This algorithm uses a morphological approach to extract signal regions from the original data. The Gaussian facet model is employed to fit the signal regions, which enhances the resistance to noise and the stability of the algorithm in diverse overlapping areas. The introduction of the extremum determination theorem of multivariate functions offers theoretical guidance for automatically locating clump centers. To guarantee that each clump is continuous, the signal regions are segmented into local regions based on gradient, and then the local regions are clustered into the clump centers based on connectivity and minimum distance to identify the regional information of each clump. The experiments conducted with both simulated and synthetic data demonstrate that FacetClumps exhibits great recall and precision rates, small location error and flux loss, and a high consistency between the region of detected clump and that of simulated clump, and the experiments demonstrate that FacetClumps is generally stable in various environments. Notably, the recall rate of FacetClumps in the synthetic data, which comprises ^13 CO ( J = 1−0) emission line of the MWISP within 11.°7 ≤ l ≤ 13.°4, 0.°22 ≤ b ≤ 1.°05, and 5 km s ^−1 ≤ v ≤ 35 km s ^−1 and simulated clumps, reaches 90.2%. Additionally, FacetClumps demonstrates satisfactory performance when applied to observational data.

We present observations of polarized dust emission at 850 μ m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense ( ${N}_{{{\rm{H}}}_{2}}\sim {10}^{22}$ –10 ^23 cm ^−2 ) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μ G in the main starless core and up to ∼90 ± 40 μ G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores.

We study the H ii regions associated with the NGC 6334 molecular cloud observed in the submillimeter and taken as part of the B -fields In STar-forming Region Observations Survey. In particular, we investigate the polarization patterns and magnetic field morphologies associated with these H ii regions. Through polarization pattern and pressure calculation analyses, several of these bubbles indicate that the gas and magnetic field lines have been pushed away from the bubble, toward an almost tangential (to the bubble) magnetic field morphology. In the densest part of NGC 6334, where the magnetic field morphology is similar to an hourglass, the polarization observations do not exhibit observable impact from H ii regions. We detect two nested radial polarization patterns in a bubble to the south of NGC 6334 that correspond to the previously observed bipolar structure in this bubble. Finally, using the results of this study, we present steps (incorporating computer vision; circular Hough transform) that can be used in future studies to identify bubbles that have physically impacted magnetic field lines.

We present BISTRO Survey 850 μ m dust emission polarization observations of the L1495A-B10 region of the Taurus molecular cloud, taken at the James Clerk Maxwell Telescope (JCMT). We observe a roughly triangular network of dense filaments. We detect nine of the dense starless cores embedded within these filaments in polarization, finding that the plane-of-sky orientation of the core-scale magnetic field lies roughly perpendicular to the filaments in almost all cases. We also find that the large-scale magnetic field orientation measured by Planck is not correlated with any of the core or filament structures, except in the case of the lowest-density core. We propose a scenario for early prestellar evolution that is both an extension to, and consistent with, previous models, introducing an additional evolutionary transitional stage between field-dominated and matter-dominated evolution, observed here for the first time. In this scenario, the cloud collapses first to a sheet-like structure. Uniquely, we appear to be seeing this sheet almost face on. The sheet fragments into filaments, which in turn form cores. However, the material must reach a certain critical density before the evolution changes from being field dominated to being matter dominated. We measure the sheet surface density and the magnetic field strength at that transition for the first time and show consistency with an analytical prediction that had previously gone untested for over 50 yr.

Several novel chalcone derivatives containing malonate and pyridine moieties were synthesized, and their structures were confirmed by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, 19F nuclear magnetic resonance, infrared, and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against cucumber mosaic virus (CMV) at 500 μg/mL. In particular, compounds 5l and 5n showed significant curative activities against CMV in vivo with 50% effective concentration (EC50) values of 186.2 and 211.5 μg/mL, respectively; these values are even better than that of ningnanmycin (330.5 μg/mL). A 3D quantitative structure–activity relationship study was carried out using the comparative molecular field analysis technique based on curative activities against CMV. Results revealed good predictive ability with cross-validated q2 and non-cross-validated r2 values of 0.517 and 0.990, respectively. Keywords: Chalcone derivatives, Malonate moiety, Pyridine moiety, Antiviral activity, Cucumber mosaic virus, 3D-QSAR

Abstract With years of development, SnTe as a homologue of PbTe has shown great potential for thermoelectric applications in p‐type conduction, and the most successful strategy is typified by alloying for maximizing the valence band degeneracy. Among the known alloy agents, MnTe has been found to be one of the most effective enabling a band convergence for an enhancement in electronic performance of SnTe, yet its solubility of only ~15 at% unfortunately prevents a full optimization in the valence band structure. This work reveals that additional PbTe alloying not only promotes the MnTe solubility to locate the optimal valence band structure but also increases the overall substitutional defects in the material for a substantial reduction in lattice thermal conductivity. In addition, PbTe alloying simultaneously optimizes the carrier concentration due to the cation size effect. These features all enabled by such a solute manipulation synergistically lead to a very high thermoelectric figure of merit, zT of ~1.5 in SnTe with a 20 at% MnTe and a 30 at% PbTe alloying (Sn0.5Mn0.2Pb0.3Te), demonstrating the effectiveness of solute manipulation for advancing SnTe and similar thermoelectrics.

We have performed combined elastic neutron diffuse, electrical transport, specific heat, and thermal conductivity measurements on the quasi–one-dimensional Ba3Co2O6(CO3)0.7 single crystal to characterize its transport properties. A modulated superstructure of polyatomic CO32− is formed, which not only interferes the electronic properties of this compound, but also reduces the thermal conductivity along the c-axis. Furthermore, a large magnetic entropy is observed to be contributed to the heat conduction. Our investigations reveal the influence of both structural and magnetic effects on its transport properties and suggest a theoretical improvement on the thermoelectric materials by building up superlattice with conducting ionic group.

Space-based gravitational wave detection programs, such as the Laser Interferometer Space Antenna (LISA) or Taiji program, obtain gravitational wave signals by measuring the change in the distance between three satellites by laser. The telescope is an important part of the measurement system, and its function is to transmit and receive laser signals. Due to changes in the space environment, the telescope will inevitably introduce additional dynamic aberrations, which will bring optical path errors to the inversion of gravitational wave signals. Taking LISA as an example, to achieve pm-level measurement accuracy at the detection frequency of 0.1 mHz–1 Hz, the stability requirements of the telescope are less than 1 pm/Hz1/2. This paper theoretically deduces the aberration types that affect the telescope’s stability and conducts simulation analysis according to the actual phase demodulation method, which verifies the theory’s correctness. In addition, using this theory, it can be concluded that under the condition that the total size of the telescope aberration is determined to be stable, reducing the ratio of rotationally symmetric aberrations such as “spherical aberration” and “defocusing” among common aberrations can significantly improve the stability of the telescope. The conclusion guides the optical system design of LISA or Taiji.

Surface imperfections or contamination on an optical smooth surface is usually inevitable and causes scattering. The directional information of the scattered ray can be related to the spatial frequency through the grating equation. On the other hand, the layout of the optical system determines whether a scattered ray will finally reach the detector according to the positions and directions of the scattered rays. Therefore, the scattering propagation in an optical system is usually band-limited and the effective optical range differs for different systems. In this paper, a method based on ray tracing is described that can statistically determine the optical scattering and the band of roughness. The results can be an essential reference for optical surface polishing and contamination control.

Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs.

Objectives: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5+ DM-ILD) is a life-threatening disease. The current study aimed to quantitatively assess the pulmonary high-resolution computed tomography (HRCT) images of MDA5+ DM-ILD by applying the radiomics approach and establish a multidimensional risk prediction model for the 6-month mortality.Methods: This retrospective study was conducted in 228 patients from two centers, namely, a derivation cohort and a longitudinal internal validation cohort in Renji Hospital, as well as an external validation cohort in Guangzhou. The derivation cohort was randomly divided into training and testing sets. The primary outcome was 6-month all-cause mortality since the time of admission. Baseline pulmonary HRCT images were quantitatively analyzed by radiomics approach, and a radiomic score (Rad-score) was generated. Clinical predictors selected by univariable Cox regression were further incorporated with the Rad-score, to enhance the prediction performance of the final model (Rad-score plus model). In parallel, an idiopathic pulmonary fibrosis (IPF)-based visual CT score and ILD-GAP score were calculated as comparators.Results: The Rad-score was significantly associated with the 6-month mortality, outperformed the traditional visual score and ILD-GAP score. The Rad-score plus model was successfully developed to predict the 6-month mortality, with C-index values of 0.88 [95% confidence interval (CI), 0.79–0.96] in the training set (n = 121), 0.88 (95%CI, 0.71–1.0) in the testing set (n = 31), 0.83 (95%CI, 0.68–0.98) in the internal validation cohort (n = 44), and 0.84 (95%CI, 0.64–1.0) in the external validation cohort (n = 32).Conclusions: The radiomic feature was an independent and reliable prognostic predictor for MDA5+ DM-ILD.

ObjectiveAnti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is a distinctive serology hallmark of dermatomyositis (DM). As an autoantigen, MDA5 is a cytoplasmic RNA recognition receptor. The aim of this study was to address the question of whether the RNA-containing immune complex (IC) formed by MDA5 and anti-MDA5 could activate type I interferon (IFN) response.MethodPatients with anti-MDA5+ DM (n = 217), anti-MDA5− DM (n = 68), anti-synthase syndrome (ASyS, n = 57), systemic lupus erythematosus (SLE, n = 245), rheumatoid arthritis (RA, n = 89), and systemic sclerosis (SSc, n = 30) and healthy donors (HD, n = 94) were enrolled in our studies. Anti-MDA5 antibody was detected by line blotting, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, and Western blotting. Cytokine profiling was determined by multiplex flow cytometry, and IFN-α was further measured by ELISA. Type I IFN-inducible genes were detected by quantitative PCR (qPCR). RNA–IC binding was analyzed by RNA immunoprecipitation. Plasmacytoid dendritic cells (pDCs) derived from healthy donors were cultivated and stimulated with MDA5 ICs with or without RNase and Toll-like receptor 7 (TLR-7) agonist. The interaction between MDA5 ICs and TLR7 was evaluated by immunoprecipitation and confocal microscopy.ResultsAccording to our in-house ELISA, the presence of anti-MDA5 antibody in 76.1% of DM patients, along with 14.3% of SLE patients who had a lower titer yet positive anti-MDA5 antibody, was related to the high level of peripheral IFN-α. ICs formed by MDA5 and anti-MDA5 were potent inducers of IFN-α via TLR-7 in an RNA-dependent manner in vitro.ConclusionOur data provided evidence of the mechanistic relevance between the anti-MDA5 antibody and type I IFN pathway.