Antibody Profiling of Pan-Cancer Viral Proteome Reveals Biomarkers for Nasopharyngeal Carcinoma Diagnosis and Prognosis.

Diagnosing, predicting disease outcome, and identifying effective treatment targets for virus-related cancers are lacking. Protein biomarkers have the potential to bridge the gap between prevention and treatment for these types of cancers. While it has been shown that certain antibodies against EBV proteins could be used to detect nasopharyngeal carcinoma (NPC), antibodies targeting are solely a tiny part of the about 80 proteins expressed by the EBV genome. Furthermore, it remains unclear what role other viruses play in NPC since many diseases are the result of multiple viral infections. For the first time, this study measured both IgA and IgG antibody responses against 646 viral proteins from 23 viruses in patients with NPC and control subjects using nucleic acid programmable protein arrays. Candidate seromarkers were then validated by ELISA using 1665 serum samples from three clinical cohorts. We demonstrated that the levels of five candidate seromarkers (EBV-BLLF3-IgA, EBV-BLRF2-IgA, EBV-BLRF2-IgG, EBV-BDLF1-IgA, EBV-BDLF1-IgG) in NPC patients were significantly elevated than controls. Additional examination revealed that NPC could be successfully diagnosed by combining the clinical biomarker EBNA1-IgA with the five anti-EBV antibodies. The sensitivity of the six-antibody signature at 95% specificity to diagnose NPC was comparable to the current clinically-approved biomarker combination, VCA-IgA, and EBNA1-IgA. However, the recombinant antigens of the five antibodies are easier to produce and standardize compared to the native viral VCA proteins. This suggests the potential replacement of the traditional VCA-IgA assay with the 5-antibodies combination to screen and diagnose NPC. Additionally, we investigated the prognostic significance of these seromarkers titers in NPC. We showed that NPC patients with elevated BLLF3-IgA and BDLF1-IgA titers in their serum exhibited significantly poorer disease-free survival, suggesting the potential of these two seromarkers as prognostic indicators of NPC. These findings will help develop serological tests to detect and treat NPC in the future.

Proteomics Platform Reveals Broad-Spectrum Nanobodies for SARS-CoV-2 Variant Neutralization.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy.

BACKGROUND: Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. METHOD: Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). RESULTS: Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). CONCLUSION: This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Substantial Attenuation of Virulence of Tembusu Virus Strain PS Is Determined by an Arginine at Residue 304 of the Envelope Protein.

The Tembusu virus (TMUV) PS strain, derived by several passages and plaque purifications in BHK-21 cells, displays markedly lower virulence in Pekin ducklings relative to a natural isolate of TMUV, but the potential virulence determinants and the in vivo mechanisms for substantial virulence attenuation of the passage variant remain unknown. Here, we constructed a series of chimeric and mutant viruses and assessed their virulence using a 2-day-old Pekin duckling model. We showed that residue 304 in the envelope (E) protein is the molecular determinant of TMUV virulence. Further investigations with mutant and parental viruses demonstrated that acquisition of positive charges at E protein residue 304 plays a critical role in substantial attenuation of neurovirulence and neuroinvasiveness, which is linked to enhanced binding affinity for glycosaminoglycans (GAGs). In Pekin ducklings infected by subcutaneous inoculation, an Arg at residue 304 in the E protein was shown to contribute to more rapid virus clearance from the circulation, markedly reduced viremia, and significantly decreased viral growth in the extraneural tissues and the central nervous system, relative to a Met at the corresponding residue. These findings suggest that the in vivo mechanism of virulence attenuation of the TMUV passage variant closely resembles that proposed previously for GAG-binding variants of other flaviviruses. Overall, our study provides insight into the molecular basis of TMUV virulence and the in vivo consequences of acquisition of a GAG-binding determinant at residue 304 in the E protein of TMUV.IMPORTANCE TMUV-related disease emerged in 2010 and has a significant economic impact on the duck industry. Although the disease was originally recognized to affect adult ducks, increasing evidence has shown that TMUV also causes severe disease of young ducklings. It is, therefore, essential to investigate the pathogenesis of TMUV infection in a young duckling model. The significance of our studies is in identifying E protein residue Arg304 as the molecular determinant for TMUV virulence and in clarifying the crucial role of positive charges at E protein residue 304 in virulence attenuation of a TMUV passage variant. These data will greatly enhance our understanding of the pathogenesis of TMUV infection in ducklings and have implications for development of a safe and efficient vaccine.

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Positive correlation of serum indoxyl sulfate level with peripheral arterial disease in hemodialysis patients.

OBJECTIVES: Indoxyl sulfate, known for its cardiovascular toxicity, is associated with vascular and coronary artery diseases and increased mortality. Peripheral arterial disease, defined by low ankle-brachial index, is associated with increased mortality in patients on hemodialysis. The present study aimed to determine the relationship between the serum indoxyl sulfate level and peripheral arterial disease in patients on maintenance hemodialysis. METHODS: The present cross-sectional, single-center study included 75 patients on maintenance hemodialysis. Serum indoxyl sulfate levels were determined by high-performance liquid chromatography-mass spectrometry. Ankle-brachial index values were measured using an automated oscillometric device. Patients with ankle-brachial indexes of < 0.9 were categorized into the low ankle-brachial index group. RESULTS: In the study cohort, 12 of the 75 patients (16.0%) had low ankle-brachial indexes. The rates of diabetes mellitus (p = 0.010) as well as the serum levels of C-reactive protein (p < 0.001) and indoxyl sulfate (p < 0.001) were higher in the low ankle-brachial index group than the normal ankle-brachial index group. The multivariable logistic regression analysis revealed that serum levels of indoxyl sulfate (odds ratio = 1.123, 95% confidence interval 1.011-1.249, p = 0.031) and C-reactive protein (each 0.1 mg/dL increase, odds ratio = 1.169, 95% confidence interval 1.018-1.343, p = 0.027) were independently associated with peripheral arterial disease in patients on maintenance hemodialysis. CONCLUSIONS: Serum indoxyl sulfate levels were associated with peripheral arterial disease in patients on maintenance hemodialysis.

Association of serum fibroblast growth factor 21 levels with skeletal muscle mass and mortality in chronic hemodialysis patients.

BACKGROUND/PURPOSE: Fibroblast growth factor 21 (FGF21) is a hormone that modulates metabolic pathways, which acts as a myokine under metabolic stress. We aimed to explore the association of serum FGF21 levels with skeletal muscle mass and mortality in patients on hemodialysis (HD). METHODS: Baseline serum FGF21 levels were measured, and a portable whole-body bioelectrical impedance device was used to assess skeletal muscle mass. One hundred twenty-four patients undergoing chronic HD were categorized into high- and low-FGF21 groups according to the median FGF21 value. RESULTS: Patients with low FGF21 values had lower body weight, body mass index, skeletal muscle mass index (SMI = skeletal muscle mass/height2), and serum triglyceride levels. Log serum FGF21 levels revealed a modest but positive correlation with SMI (r = 0.30, p = 0.001) and independently predicted SMI after multiple adjustment (ß = 1.59, p = 0.027). During a median follow-up period of 66 months, all-cause mortality and cardiovascular death rates did not differ significantly between the high- and low-FGF21 groups. We also failed to demonstrate FGF21 as an independent predictor of all-cause mortality. CONCLUSION: Serum FGF21 levels exhibited a positive association with skeletal muscle mass but were not predictive of mortality in patients undergoing chronic HD.

Serum Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating osteocalcin can be expressed by osteoblasts and even by osteoblast-like cells in vessel walls, and it is often associated with arterial stiffness. Our study aims to examine the potential association between osteocalcin levels and endothelial function among kidney transplant (KT) recipients. MATERIALS AND METHODS: Fasting blood samples were obtained from 68 KT recipients. To measure the endothelial function and vascular reactivity index (VRI), a digital thermal monitoring test (VENDYS) was used. A commercial enzyme-linked immunosorbent assay kit was also utilized to measure serum total osteocalcin levels. In this study, a VRI of less than 1.0 indicated poor vascular reactivity; a VRI of 1.0-2.0 indicated intermediate vascular reactivity; and a VRI of 2.0 or higher indicated good vascular reactivity. RESULTS: Our findings show that 8 KT recipients (11.8%) had poor vascular reactivity (VRI < 1.0), 26 (38.2%) had intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 34 (50%) had good vascular reactivity. Increased serum osteocalcin levels (p < 0.001) were found to be associated with poor vascular reactivity. Advanced age (r = -0.361, p = 0.002), serum alkaline phosphate level (r = -0.254, p = 0.037), and log-transformed osteocalcin levels (r = - 0.432, p < 0.001) were identified to be negatively correlated with VRI in KT recipients. Multivariable forward stepwise linear regression analysis revealed that the serum level of osteocalcin (ß = -0.391, adjusted R2 change = 0.174; p < 0.001) and advanced age (ß = -0.308, adjusted R2 change = 0.084; p = 0.005) were significantly and independently associated with VRI in KT recipients. CONCLUSIONS: Higher serum osteocalcin level was associated with lower VRI and poorer endothelial dysfunction among KT recipients.

Pathogenicity of egg-type duck-origin isolate of Tembusu virus in Pekin ducklings.

BACKGROUND: Tembusu virus (TMUV) usually affects adult ducks, causing a severe drop of egg production. It has also been shown to be pathogenic in commercial Pekin ducklings below 7 weeks of age. Here, we report a TMUV-caused neurological disease in young egg-type ducklings and the pathogenicity of the egg-type duck-origin TMUV isolates in meat-type Pekin ducklings. RESULTS: The disease occurred in 25 to 40-day-old Jinding ducklings in China, and was characterized by paralysis. Gross lesions were lacking and microscopic lesions appeared chiefly in brain and spleen. Inoculation in embryonated duck eggs resulted in isolation of TMUV Y and GL. The clinical signs and microscopic lesions observed in the spontaneously infected egg-type ducks were repeated in Pekin ducklings by experimental infection. Notably, both Y and GL strains caused 100% mortality in the case of 2-day-old inoculation by intracerebral route. High mortalities (80 and 70%) also occurred following infection of the Y virus at 2 days of age by intramuscular route and at 9 days of age by intracerebral route. CONCLUSIONS: These findings demonstrate that the egg-type duck-origin TMUVs exhibit high pathogenicity in Pekin ducklings, and that the severity of the disease in ducklings is dependent on the infection route and the age of birds at the time of infection. The availability of the highly pathogenic TMUV strains provides a useful material with which to begin investigations into the molecular basis of TMUV pathogenicity in ducks.

Developing a Decision-Aid Website for Breast Cancer Surgery: An Action Research Approach.

BACKGROUND: Patients with early-stage breast cancer have numerous options when choosing the type of breast surgery method to be applied. Each of these options lead to a similar long-term survival rate, but result in significant differences in appearance, function, cost, recurrence rate, and various other relevant considerations. However, the time available for detailed communication with each patient is often limited in clinics, which puts these women under great psychological stress and can hinder their surgery-related decision making. OBJECTIVE: The objective of this study was to develop a multipurpose surgery decision-making website providing medical information, psychological support, and decision-related simulation for women during breast cancer surgery-related decision making. METHODS: Using the 4 steps of action research, which involve multigroup teamwork via regular team meetings, the following were performed: (1) Planning: searching, analyzing, and evaluating health websites to consensually decide the major infrastructure; (2) Action: work was performed simultaneously in 4 groups, which consisted of medical information collection and editing, patient interviews and data extraction, webpage content design, and programming to create or host the website; (3) Evaluation: the website was tested by clinical experts and focus groups of former breast cancer patients to assess its effectiveness and pinpoint appropriate improvements; and (4) Reflection: constant dialogue was conducted between the various participants at each step, which was used as the foundation and motivation of next plan-action-evaluation-reflection circle. RESULTS: Using the action research approach, we completed the development of our website, which includes the following: (1) "Woman's Voice"-an animated comic depicting the story of a female breast cancer patient with interspersed questions for the users that will help them better empathize with the experience; (2) "Cancer Information Treasure House"-providing breast cancer surgery-related information through text, tables, pictures and a presentation video; (3) "Decision-making Simulator"-helping patients think through and check the pros and cons of the different surgical options via visual-based interactions including "Stairs Climbing" and "Fruit of Hope"; and (4) "Recommended Links"-providing reliable websites for further reference. Additionally, we have further improved the website based on the feedback received from postsurgery breast cancer patients and clinicians. We hope to continue improving to better meet both the patients' and health providers' needs and become a practical decision-making aid for patients undergoing breast cancer surgery. CONCLUSIONS: We have created the first breast cancer surgery decision-making assistance tool in Taiwan using a "Web-based" and multifunctional website design. This site aims to provide health care knowledge, psychological healing, and emotional support functions, as well as decision-making capability enhancement simulations. We look forward to assisting breast cancer patients in their decision-making process and expect our website to increase patient's autonomy and improve their communication with clinicians.

Developing a Web-Based Comic for Newly Diagnosed Women With Breast Cancer: An Action Research Approach.

BACKGROUND: Personal narratives have been seen as a useful way of communicating about cancer treatment options and providing recovery information. Many printed versions of such material are available, including comics that explore the individual memories of patients who have gone through cancer treatment. These studies have been used to orientate patients, patients' relatives, and physicians. However, only a few Web-based comics have been specifically designed for patients with breast cancer and used as aids to decision making. OBJECTIVE: We aimed to describe the developmental process of creating an animated comic as a Web-based surgery decision-making tool; the comic was aimed at illustrating the feelings, thoughts, and meanings when a patient suffers from breast cancer. This was done by recounting the symptoms, diagnostic process, treatments, and treatment effects of such women from the diagnosis stage onward. METHODS: Using cycles of planning, action, evaluation, and reflection, which involved collaborative work, action research was conducted to develop a Web-based animated comic. The stages of action research consisted of (1) semistructured and in-depth interviews to collect experiences of women with breast cancer; (2) construction of an animated comic by editors, graphics designers, dubbers, and information technology engineers; (3) redrawing of pictures of the comic after gathering feedback from a breast surgeon; and (4) evaluation of the Web-based animated comic using 6 patient focus groups. RESULTS: The comic was produced and showcased on the website "The Network of Making-decision Aids for Breast Cancer Surgery"; the comic was accompanied by soft music and audio explanations. The comic functions as a personal statement that describes experiencing breast cancer. The animated comic consists of 8 chapters, based on the 8 themes deducted from the findings obtained during the analysis of relevant interviews. The 8 chapters include (1) the appearance of a lump; (2) confirmation by medical diagnosis; (3) the uncertainty of waiting (4) fear of life-threatening disease; (5) choosing life over despair; (6) being brave and deciding to undergo treatment; (7) choosing the type of surgery; and (8) being reborn. CONCLUSIONS: Using action research, this study illustrated that the comic that sheds light on issues of feelings, emotions, and thoughts that are present when a woman is diagnosed with breast cancer and provides a communication medium to explain the steps in the process. Meanwhile, it implies that hope will be able to overcome the challenges that will be faced. Within the Web-based decision aid for patients with breast cancer, the animated comic acts as an information resource and is aimed at patients' understanding of impacts of emotions arising when suffering from breast cancer. It is potentially applicable as a therapeutic tool that facilitates self-reflection and self-healing among newly diagnosed patients with breast cancer.

Pathogenicity of a variant goose parvovirus, from short beak and dwarfism syndrome of Pekin ducks, in goose embryos and goslings.

The pathogenicity of a variant goose parvovirus (GPV), isolated from short beak and dwarfism syndrome of Pekin ducks (strain Cherry Valley), was investigated in embryonating goose eggs and goslings. The virus was easily grown in GPV antibody-free goose embryos and caused high mortality and severe lesions of goose embryos, indicating that the variant GPV has good adaptation and high pathogenicity to embryonated goose eggs similar to the classical GPV. Like the third egg-passage virus (strain H) of a classical GPV, the third egg-passage virus (strain JS1) of the variant GPV caused Derzsy's disease in 2-day-old goslings with high mortality. The findings suggest that the variant GPV strain, which had specifically adapted to Pekin ducks, still retained high pathogenicity for its original host. The mortality (73.3-80%) caused by the first and third egg-passages of the variant GPV was somewhat lower than that (93.3%) caused by the third passage virus of the classical GPV, reflecting the higher pathogenicity of the classical GPV for its original host. These findings are likely to reinforce the importance of surveillance for parvoviruses in different waterfowl species and stimulate further study to elucidate the impact of mutations in the GPV genome on its pathogenicity to goslings and ducks.

Genetic characterization of two novel megriviruses in geese.

Two goose megriviruses (W18 and HN56) were detected and sequenced. Both viruses possessed megrivirus-like genomic features, including unusually long genomes (9840 and 10 101 nt). W18 and HN56 were very similar to duck megrivirus (DMV) in the P2 and P3 regions, but much less similar in the P1 and 2A1 regions. HN56 may be a potential recombinant virus, with a distinct P1 region possibly originating from an unknown picornavirus. W18 may represent a novel type of DMV, showing a P1 sequence identity of 67 %. Similar levels (64-68 %) of P1 sequence identity were also displayed by melegrivirus A with W18 and DMV, demonstrating an equal genetic separation of the capsid region among W18, DMV and melegrivirus A. For the 2A1 region, the divergence among W18, HN56 and DMV was remarkable, involving point mutations and a long insertion/deletion. The present work contributes to the understanding of unique features and phylogeny of megriviruses.

Modification of the internal ribosome entry site element impairs the growth of foot-and-mouth disease virus in porcine-derived cells.

The 5' untranslated region (5'UTR) of foot-and-mouth disease virus (FMDV) contains an internal ribosome entry site (IRES) that facilitates translation initiation of the viral ORF in a 5' (m7GpppN) cap-independent manner. IRES elements are responsible for the virulence phenotypes of several enteroviruses. Here, we constructed a chimeric virus in which the IRES of FMDV was completely replaced with that of bovine rhinitis B virus (BRBV) in an infectious clone of serotype O FMDV. The resulting IRES-replaced virus, FMDV(BRBV), replicated as efficiently as WT FMDV in hamster-derived BHK-21 cells, but was restricted for growth in porcine-derived IBRS-2, PK-15 and SK-6 cells, which are susceptible to WT FMDV. To identify the genetic determinants of FMDV underlying this altered cell tropism, a series of IRES-chimeric viruses were constructed in which each domain of the FMDV IRES was replaced with its counterpart from the BRBV IRES. The replication kinetics of these chimeric viruses in different cell lines revealed that the growth restriction phenotype in porcine-derived cells was produced after the replacement of domain 3 or 4 in the FMDV IRES. Furthermore, the change in FMDV cell tropism due to IRES replacement in porcine-derived cells was mainly attributed to a decline in cell-specific IRES translation initiation efficiency. These findings demonstrate that IRES domains 3 and 4 of FMDV are novel cell-specific cis-elements for viral replication in vitro and suggest that IRES-mediated translation determines the species specificity of FMDV infection in vivo.

Selection and characterization of an acid-resistant mutant of serotype O foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) loses infectivity and immunogenicity due to its disassembly in culture environments below pH 6.8. To study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of inactivated FMD vaccines during the manufacturing process, type O FMDV mutants with increased resistance to acid inactivation were selected, and the genes encoding their capsid proteins were sequenced. Three amino acid substitutions (VP1 N17D, VP2 D86A, and VP4 S73N) were found in all of the mutants. When these substitutions were introduced into seven infectious FMDV clones alone or combined, a single amino acid substitution in the VP1 protein, N17D, which also appears in type C FMDV acid-resistant mutants, was found to be responsible for the increased resistance to acid inactivation for type O FMDV. In addition, although viral fitness was reduced under standard culture conditions, viral growth kinetics and virulence were not significantly altered in the rescued mutant virus rN17D with the VP1 N17D substitution. Importantly, the N17D substitution could confer improved immunogenicity to the mutant virus rN17D under acidic conditions compared with its parental virus O/YS/CHA/05. These results demonstrate that the N17D substitution in VP1 is the molecular determinant of the acid-resistant phenotype in type O FMDV, indicating the potential for use of this substitution to improve the acid stability of inactivated FMD vaccines during the vaccine production process.

Optimization of terminal area arrival flight sorting based on an improved sparrow search algorithm.

At present, airspace congestion and flight delays have become widespread concerns. This study aims to optimize the sequencing of arrival flights in the terminal area of multirunway airports. Considering the constraints of multiple runways, slant intervals and moving flight positions, this article establishes an optimization model for arrival flight sequencing in a multirunway airport terminal area. Accordingly, an improved sparrow search algorithm (ISSA) is proposed based on Chebyshev chaotic mapping, the golden sine strategy, and the variable neighborhood strategy. Through six basic test functions, the ISSA is compared with particle swarm optimization, the whale optimization algorithm, the genetic algorithm, and other algorithms to verify its superiority. Finally, two sets of instance data from Kunming Changshui Airport were used for experiments. The results show that the total delay times (TDTs) of small-scale flights (number of aircraft: 29) and large-scale flights (number of aircraft: 147) are 55.3% and 20.5% lower, respectively, than those of the first-come-first-served algorithm. The superiority of the ISSA designed in this article is verified, and it can significantly reduce the TDTs of arrival flights. It is suitable for optimizing arrival flights during peak hours at most airports. This approach provides theoretical support for optimizing the sorting of flights in terminal areas.

Constructing an Ensemble Model and Niche Comparison for the Management Planning of Eucalyptus Longhorned Borer Phoracantha semipunctata under Climate Change.

Phoracantha semipunctata is a destructive invasive alien forest pest worldwide. It primarily damages the eucalyptus via adults, affecting almost all parts of the eucalyptus. Its larvae develop in almost all major tissues of the plant. Phoracantha semipunctata spreads both via the migration of adults and global trade in intercontinental translocation. Currently, this pest has spread to six continents worldwide, except Antarctica, resulting in substantial economic losses. Based on global occurrence data and environmental variables, the potential global geographical distribution of P. semipunctata was predicted using an ensemble model. The centroid shift, overlap, unfilling, and expansion scheme were selected to assess niche dynamics during the global invasion process. Our results indicated that the AUC and TSS values of the ensemble model were 0.993 and 0.917, respectively, indicating the high prediction accuracy of the model. The distribution pattern of P. semipunctata is primarily attributed to the temperature seasonality (bio4), mean temperature of the warmest quarter (bio10), and human influence index variables. The potential geographical distribution of P. semipunctata is primarily in western and southwestern Asia, western Europe, western and southern North America, southern South America, southern Africa, and eastern and southern Oceania. The potential geographical distribution of P. semipunctata showed a downward trend in the 2030s and the 2050s. The distribution centroid showed a general tendency to shift southward from the near-current to future climate. Phoracantha semipunctata has largely conserved its niche during the global invasion process. More attention should be paid to the early warning, prevention, and control of P. semipunctata in the countries and regions where it has not yet become invasive.

Atomistic insights into migration mechanism of graphene-based membranes on soil mineral phases.

Graphene-based membranes (GBM) will migrate in the soil and enter the groundwater system or plant roots, which will eventually pose potential risks to human beings. The migration mechanism of GBM depends on the interface behavior of complex soil components. Herein, we use molecular dynamics (MD) simulations to probe the interface behavior between GBM and three type minerals (quartz, calcite and kaolinite). Based on the investigation of binding energy, maximum pulling force and barrier energy, the order of the difficulty of GBM adsorption and desorption on the three minerals from small to large is roughly: quartz, calcite and kaolinite respectively. The graphene-oxide (GO), improves the binding energy and energy barrier, making GBM difficult to migrate in soil. Remarkably, a larger GBM sheet and high velocity external load improve GBM migration in soil to a certain extent. These investigations give the dynamic information on the GBM/mineral interaction and provide nanoscale insights into the migration mechanisms of GBM in soil.

Profiling of SARS-CoV-2 neutralizing antibody-associated antigenic peptides signature using proteome microarray.

The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS-CoV-2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID-19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S-82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10-3), were closely associated with the presence of SARS-CoV-2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID-19 cases in 2020, S82-IgG titers were higher in NAbs-positive samples (p = 0.002) than in NAbs-negative samples using enzyme-linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82-IgG titers, NAb titers were significantly higher in the samples with higher S82-IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay-associated signatures of SARS-CoV-2 NAbs.

Proteomics Landscape Mapping of Organ-Resolved Behçet's Disease Using In-Depth Plasma Proteomics for Identifying Hyaluronic Binding Protein 2 Expression Associated With Vascular Involvement.

OBJECTIVE: This study was undertaken to elucidate the pathogenesis and heterogeneity of Behçet's disease (BD) involving different organs using in-depth proteomics to identify the biomarkers for clinical assessment and treatment of patients with BD. METHODS: We measured the expression levels of proteins in plasma samples from 98 patients with BD and from 31 healthy controls using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the BD group and constructed a proteomics landscape of organ-resolved BD pathogenesis. We then validated the biomarkers of disease severity and the vascular subset in an independent cohort of 108 BD patients and 29 healthy controls using an enzyme-linked immunosorbent assay. RESULTS: The BD group had 220 differentially expressed proteins, which discriminated between BD patients (88.6%) and healthy controls (95.5%). The bioinformatics analyses revealed different biologic processes associated with BD pathogeneses, including complement activation, wound healing, angiogenesis, and leukocyte-mediated immunity. Furthermore, the constructed proteomics landscape of organ-resolved BD identified proteomics features of BD associated with different organs and protein targets that could be used for the development of therapeutic treatment. Hyaluronic binding protein 2, tenascin, and serpin A3 were validated as potential biomarkers for the clinical assessment of vascular BD and treatment targets. CONCLUSION: Our results provide valuable insight into the pathogenesis of organ-resolved BD in terms of proteomics characteristics and potential biomarkers for clinical assessment and potential therapies for vascular BD.