Parameter identifiability of a within-host SARS-CoV-2 epidemic model.

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

Evaluation of age-structured vaccination strategies for curbing the disease spread.

Age structure is one of the crucial factors in characterizing the heterogeneous epidemic transmission. Vaccination is regarded as an effective control measure for prevention and control epidemics. Due to the shortage of vaccine capacity during the outbreak of epidemics, how to design vaccination policy has become an urgent issue in suppressing the disease transmission. In this paper, we make an effort to propose an age-structured SVEIHR model with the disease-caused death to take account of dynamics of age-related vaccination policy for better understanding disease spread and control. We present an explicit expression of the basic reproduction number R 0 , which determines whether or not the disease persists, and then establish the existence and stability of endemic equilibria under certain conditions. Numerical simulations are illustrated to show that the age-related vaccination policy has a tremendous influence on curbing the disease transmission. Especially, vaccination of people over 65 is better than for people aged 21-65 in terms of rapid eradication of the disease in Italy.

Predictive value of the Adult Comorbidity Evaluation 27 on adverse surgical outcomes and survival in elderly with advanced epithelial ovarian cancer undergoing cytoreductive surgery.

OBJECTIVE: We aimed to evaluate the ability of Adult Comorbidity Evaluation 27 (ACE-27) to predict perioperative outcomes and survival in elderly women with advanced epithelial ovarian cancer (AEOC) undergoing cytoreductive surgery. METHODS: We collected patients with AEOC in our hospital between January 1, 2012 and January 1, 2021. Patients younger than 65 years old or those with non-epithelial ovarian cancer were excluded. ACE-27 was applied retrospectively to assess comorbidities in the selected patients, who were then classified into two groups based on their ACE-27 scores: low ACE-27 score group (none to mild) and high ACE-27 score group (moderate to severe). RESULTS: A total of 222 elderly women with AEOC were included, of whom 164 patients accepted debulking surgery. Among those who have undergone surgery, Clavien-Dindo grade III + perioperative complications or unintended intensive care unit (ICU) admission occurred more often in patients of high ACE-27 score group, with statistically significant difference (odds ratio [OR]: 4.21, 95% confidence interval [CI], 1.28-14.35, p = 0.018). Further stratified analyses by age, BMI, FIGO stage and pathology also prove that OS of patients graded severe was shorter than patients graded none to moderate in cohort of age < 70, BMI < 25 kg/m2, FIGO III stage and pathology of serous, respectively. Kaplan-Meier survival curves analyzed by log-rank test showed that the overall survival (OS) of patients with severe comorbidities were shorter than with none to moderate (HR 3.25, 95%CI 1.55-6.79, p = 0.002). CONCLUSIONS: Our findings demonstrate the ability of ACE-27 to predict grade III + perioperative complications or unintended ICU admission and survival in elderly patients with AEOC. This highlights the possibility for ACE-27 to play an instrumental role in identifying AEOC patients who are more susceptible to adverse surgical outcomes and have a poor survival rate and assisting in decisions regarding treatment.

High mono-rhamnolipids production by a novel isolate Pseudomonas aeruginosa LP20 from oily sludge: characterization, optimization, and potential application.

This study aims to isolate microbial strains for producing mono-rhamnolipids with high proportion. Oily sludge is rich in petroleum and contains diverse biosurfactant-producing strains. A biosurfactant-producing strain LP20 was isolated from oily sludge, identified as Pseudomonas aeruginosa based on phylogenetic analysis of 16S rRNA. High-performance liquid chromatography-mass spectrometry results indicated that biosurfactants produced from LP20 were rhamnolipids, mainly containing Rha-C8-C10, Rha-C10-C10, Rha-Rha-C8-C10, Rha-Rha-C10-C10, Rha-C10-C12:1, and Rha-C10-C12. Interestingly, more mono-rhamnolipids were produced by strain LP20 with a relative abundance of 64.5%. Pseudomonas aeruginosa LP20 optimally produced rhamnolipids at a pH of 7.0 and a salinity of 0.1% using glycerol and nitrate. The culture medium for rhamnolipids by strain LP20 was optimized by response surface methodology. LP20 produced rhamnolipids up to 6.9 g L-1, increased by 116%. Rhamnolipids produced from LP20 decreased the water surface tension to 28.1 mN m-1 with a critical micelle concentration of 60 mg L-1. The produced rhamnolipids emulsified many hydrocarbons with EI24 values higher than 56% and showed antimicrobial activity against Staphylococcus aureus and Cladosporium sp. with inhibition rates 48.5% and 17.9%, respectively. Pseudomonas aeruginosa LP20 produced more proportion of mono-rhamnolipids, and the LP20 rhamnolipids exhibited favorable activities and promising potential in microbial-enhanced oil recovery, bioremediation, and agricultural biocontrol.

Enhancing cell-scale performance via sustained release of the varicella-zoster virus antigen from a microneedle patch under simulated microgravity.

The immune system of astronauts might become weakened in the microgravity environment in space, and the dormant varicella-zoster virus (VZV) in the body might be reactivated, seriously affecting their work and safety. For working in orbit for the long term, there is currently no efficient and durable delivery system of general vaccines in a microgravity environment. Accordingly, based on the previous foundation, we designed, modified, and synthesized a biodegradable and biocompatible copolymer, polyethylene glycol-polysulfamethazine carbonate urethane (PEG-PSCU) that could be mainly adopted to fabricate a novel sustained-release microneedle (S-R MN) patch. Compared with conventional biodegradable microneedles, this S-R MN patch could not only efficiently encapsulate protein vaccines (varicella-zoster virus glycoprotein E, VZV gE) but also further prolong the release time of VZV gE in a simulated microgravity (SMG) environment. Eventually, we verified the activation of dendritic cells by VZV gE released from the S-R MN patch in an SMG environment and the positive bioeffect of activated dendritic cells on lymphocytes using an in vitro lymph node model. This study is of great significance for the exploration of long-term specific immune responses to the VZV in an SMG environment.

Signatures of tumor-associated macrophages correlate with treatment response in ovarian cancer patients.

Ovarian cancer (OC) ranks as the second leading cause of death among gynecological cancers. Numerous studies have indicated a correlation between the tumor microenvironment (TME) and the clinical response to treatment in OC patients. Tumor-associated macrophages (TAMs), a crucial component of the TME, exert influence on invasion, metastasis, and recurrence in OC patients. To delve deeper into the role of TAMs in OC, this study conducted an extensive analysis of single-cell data from OC patients. The aim is to develop a new risk score (RS) to characterize the response to treatment in OC patients to inform clinical treatment. We first identified TAM-associated genes (TAMGs) in OC patients and examined the protein and mRNA expression levels of TAMGs by Western blot and PCR experiments. Additionally, a scoring system for TAMGs was constructed, successfully categorizing patients into high and low RS subgroups. Remarkably, significant disparities were observed in immune cell infiltration and immunotherapy response between the high and low RS subgroups. The findings revealed that patients in the high RS group had a poorer prognosis but displayed greater sensitivity to immunotherapy. Another important finding was that patients in the high RS subgroup had a higher IC50 for chemotherapeutic agents. Furthermore, further experimental investigations led to the discovery that THEMIS2 could serve as a potential target in OC patients and is associated with EMT (epithelial-mesenchymal transition). Overall, the TAMGs-based scoring system holds promise for screening patients who would benefit from therapy and provides valuable information for the clinical treatment of OC.

Multi-omics Analysis Identifies Hypoxia Subtypes and S100A2 as an Immunosuppressive Factor in Cervical Cancer.

Cervical cancer is a common gynecological oncology. Growing evidence indicates hypoxia plays an important role in tumor progression and immunity. However, no study has examined the hypoxia landscape in cervical cancer. In this study, using hierarchical clustering, we identified three hypoxia subtypes in cervical cancer samples from The Cancer Genome Atlas dataset according to formerly described hypoxia-related genes. The overall survival time, hypoxic features, genomics, and immunological characteristics of these subtypes existed distinct differences. We also created a hypoxia score by principle component analysis for dimension reduction. The hypoxiaScore was an effective prognostic biomarker validated by GSE44001 and was associated with immunotherapy response. Furthermore, combined with single-cell RNA-sequence (scRNA-seq) and experiments, S100A2 was identified as an immunosuppressive factor induced by hypoxia and regulated expression of PD-L1. S100A2 also served as an oncogene promoting the proliferation and migration of cervical cancer cells. These findings depicted a new hypoxia-based classification and identified S100A2 as a potential therapeutic target for cervical cancer, thereby advancing the understanding of immunotherapy resistance mechanisms and cervical cancer genetic markers.

Rational Design of Bioactive Materials for Bone Hemostasis and Defect Repair.

Everyday unnatural events such as trauma, accidents, military conflict, disasters, and even medical malpractice create open wounds and massive blood loss, which can be life-threatening. Fractures and large bone defects are among the most common types of injuries. Traditional treatment methods usually involve rapid hemostasis and wound closure, which are convenient and fast but may result in various complications such as nerve injury, deep infection, vascular injury, and deep hematomas. To address these complications, various studies have been conducted on new materials that can be degraded in the body and reduce inflammation and abscesses in the surgical area. This review presents the latest research progress in biomaterials for bone hemostasis and repair. The mechanisms of bone hemostasis and bone healing are first introduced and then principles for rational design of biomaterials are summarized. After providing representative examples of hemostatic biomaterials for bone repair, future challenges and opportunities in the field are proposed.

Rich dynamics of a bidirectionally linked immuno-epidemiological model for cholera.

Cholera is an environmentally driven disease where the human hosts both ingest the pathogen from polluted environment and shed the pathogen to the environment, generating a two-way feedback cycle. In this paper, we propose a bidirectionally linked immuno-epidemiological model to study the interaction of within- and between-host cholera dynamics. We conduct a rigorous analysis for this multiscale model, with a focus on the stability and bifurcation properties of each feasible equilibrium. We find that the parameter that represents the bidirectional connection is a key factor in shaping the rich dynamics of the system, including the occurrence of the backward bifurcation and Hopf bifurcation. Numerical results illustrate a practical application of our model and add new insight into the prevention and intervention of cholera epidemics.

CNIH4 governs cervical cancer progression through reducing ferroptosis.

Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.

The Comprehensive Analysis Illustrates the Role of CDCA5 in Breast Cancer: An Effective Diagnosis and Prognosis Biomarker.

Background: Several studies have been conducted to investigate the role of cell division cycle-associated 5 (CDCA5) in cancer. Its role in breast cancer, however, remains unknown. Methods: The Gene Expression Omnibus and Cancer Genome Atlas Program databases provided the open-access information needed for the research. The CCK8 and colony formation assays were used to measure cell proliferation. The capacity of breast cancer cells to invade and migrate was assessed using the transwell assay. Results: In our study, CDCA5 was identified as the interested gene through a series of bioinformatics analysis. We found a higher CDCA5 expression level in tissue and cells of breast cancer. Meanwhile, CDCA5 has been linked to increased proliferation, invasion, and migration of breast cancer cells, which was also associated with worse clinical features. The biochemical pathways, in which CDCA5 was engaged, were identified using biological enrichment analysis. Immune infiltration research revealed that CDCA5 was linked to enhanced activity of several immune function terms. Meanwhile, DNA methylation might be responsible for the aberrant level of CDCA5 in tumor tissue. In addition, CDCA5 could significantly increase the paclitaxel and docetaxel sensitivity, indicating that it has the potential for clinical application. Also, we found that CDCA5 is mainly localized in cell nucleoplasm. Moreover, in the breast cancer microenvironment, we found that CDCA5 is mainly expressed in malignant cells, proliferation T cells, and neutrophils. Conclusion: Overall, our findings suggest that CDCA5 is a potential prognostic indicator and target for breast cancer, which can indicate the direction of the relevant research.

TFAP2A promotes cervical cancer via a positive feedback pathway with PD­L1.

Transcription factor AP­2 alpha (TFAP2A) is a critical cell growth regulator that is overexpressed in various tumor tissues. However, its role in the development of cervical cancer remains unknown. In the present study, public databases were thus explored and a higher expression of TFAP2A was found in cervical cancer. A total of 131 clinical samples were collected and it was also identified that TFAP2A was highly expressed in cervical tumor tissues. TFAP2A was also found to be associated with a higher tumor stage, lymph node metastasis and a poor patient survival. In vitro experiments revealed that the knockdown of TFAP2A inhibited the proliferation and migration of cervical cancer cells and promoted apoptosis. Furthermore, it was observed that TFAP2A could bind the programmed death­ligand 1 (PD­L1) promoter region and PD­L1 rescued TFAP2A expression. In vivo experiments also revealed that TFAP2A promoted tumor growth. Collectively, in the present study it was demonstrated that TFAP2A is a transcription factor of PD­L1 and a prognostic factor with clinical value, identifying a positive feedback loop of TFAP2A/PD­L1.

2-Deoxy-D-glucose simultaneously targets glycolysis and Wnt/ß-catenin signaling to inhibit cervical cancer progression.

Cervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2-Deoxy-D-glucose (2-DG) is a glycolysis inhibitor that acts on hexokinase, the first rate-limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2-DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa. Cell function experiments revealed that 2-DG significantly inhibited cell growth, migration, and invasion, and induced G0/G1 phase arrest at non-cytotoxic concentrations. In addition, we found that 2-DG down-regulated Wingless-type (Wnt)/ß-catenin signaling. Mechanistically, 2-DG accelerated the degradation of ß-catenin protein, which resulted in the decrease of ß-catenin expression in both nucleus and cytoplasm. The Wnt agonist lithium chloride and ß-catenin overexpression vector could partially reverse the inhibition of malignant phenotype by 2-DG. These data suggested that 2-DG exerted its anti-cancer effects on cervical cancer by co-targeting glycolysis and Wnt/ß-catenin signaling. As expected, the combination of 2-DG and Wnt inhibitor synergistically inhibited cell growth. It is noteworthy that, down-regulation of Wnt/ß-catenin signaling also inhibited glycolysis, indicating a similar positive feedback regulation between glycolysis and Wnt/ß-catenin signaling. In conclusion, we investigated the molecular mechanism by which 2-DG inhibits the progression of cervical cancer in vitro, elucidated the interregulation between glycolysis and Wnt/ß-catenin signaling, and preliminarily explored the effect of combined targeting of glycolysis and Wnt/ß-catenin signaling on cell proliferation, which provides more possibilities for the formulation of subsequent clinical treatment strategies.

TRIM6 Reduces Ferroptosis and Chemosensitivity by Targeting SLC1A5 in Lung Cancer.

Objective: Ferroptosis, a newly identified form of cell death, plays critical roles in the development and chemoresistance of lung cancer. Tripartite motif 6 (TRIM6) acts as an E3-ubiquitin ligase and can promote the progression of human colorectal cancer. The present study is aimed at investigating its role and potential mechanisms in lung cancer. Methods: Lentiviral vectors were used to overexpress or knock down TRIM6 in human lung cancer cells. Cell survival, colony formation, lipid peroxidation, intracellular iron levels, and other ferroptotic markers were examined. The role of TRIM6 on ferroptosis and chemosensitivity was further tested in mouse tumor xenograft models. Results: TRIM6 was highly expressed in human lung cancer tissues and cells, and its expression in the lung cancer cells was further increased by ferroptotic stimulation. TRIM6 overexpression inhibited, while TRIM6 silence promoted erastin- and RSL3-induced glutaminolysis and ferroptosis in the lung cancer cells. Mechanistically, TRIM6 directly interacted with solute carrier family 1 member 5 to promote its ubiquitination and degradation, thereby inhibiting glutamine import, glutaminolysis, lipid peroxidation, and ferroptotic cell death. Moreover, we observed that TRIM6 overexpression reduced the chemotherapeutic effects of cisplatin and paclitaxel. In contrast, TRIM6 silence sensitized human lung cancer cells to cisplatin and paclitaxel in vivo and in vitro. Conclusion: Our findings for the first time define TRIM6 as a negative regulator of ferroptosis in the lung cancer cells, and TRIM6 overexpression enhances the resistance of human lung cancer cells to chemotherapeutic drugs. Overall, targeting TRIM6 may help to establish novel strategies to treat lung cancer.

Analysis of an environmental epidemic model based on voluntary vaccination policy.

With the worsening of the environment and the increasing international trade, indirect transmission from exposure to contaminants in the surrounding environment has become an overlooked mode of transmission. This paper proposes a new game-theoretic model considering voluntary vaccination against imperfection and the unique integration of human-to-human and virus-to-human transmission routes. Based on the individual-based risk assessment update rule (IB-RA), the strategy-based risk assessment update rule (SB-RA), and the direct commitment update rule (DC), the different effects of individuals' behaviors on disease prevalence are analyzed. To find the effect of indirect transmission on epidemic transmission, we compare our model with the traditional SVIR model. Finally, it can be seen that indirect transmission mechanisms will aggravate the spread of epidemics.

Temporal-spatial analysis of a foot-and-mouth disease model with spatial diffusion and vaccination.

Foot-and-mouth disease is an acute, highly infectious, and economically significant transboundary animal disease. Vaccination is an efficient and cost-effective measure to prevent the transmission of this disease. The primary way that foot-and-mouth disease spreads is through direct contact with infected animals, although it can also spread through contact with contaminated environments. This paper uses a diffuse foot-and-mouth disease model to account for the efficacy of vaccination in managing the disease. First, we transform an age-space structured foot-and-mouth disease into a diffusive epidemic model with nonlocal infection coupling the latent period and the latent diffusive rate. The basic reproduction number, which determines the outbreak of the disease, is then explicitly formulated. Finally, numerical simulations demonstrate that increasing vaccine efficacy has a remarkable effect than increasing vaccine coverage.

Effects of co-infection on vaccination behavior and disease propagation.

Coinfection is the process of an infection of a single host with two or more pathogen variants or with two or more distinct pathogen species, which often threatens public health and the stability of economies. In this paper, we propose a novel two-strain epidemic model characterizing the co-evolution of coinfection and voluntary vaccination strategies. In the framework of evolutionary vaccination, we design two game rules, the individual-based risk assessment (IB-RA) updated rule, and the strategy-based risk assessment (SB-RA) updated rule, to update the vaccination policy. Through detailed numerical analysis, we find that increasing the vaccine effectiveness and decreasing the transmission rate effectively suppress the disease prevalence, and moreover, the outcome of the SB-RA updated rule is more encouraging than those results of the IB-RA rule for curbing the disease transmission. Coinfection complicates the effects of the transmission rate of each strain on the final epidemic sizes.

Long non-coding RNA LBX2-AS1 predicts poor survival of colon cancer patients and promotes its progression via regulating miR-627-5p/RAC1/PI3K/AKT pathway.

Colon cancer is one of the most prevalent malignant tumors across the world. Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) take part in colon cancer development. Our study intends to explore the expression characteristics of LBX2-AS1, a novel lncRNA, in colon cancer and its underlying mechanisms. The results illustrated that LBX2-AS1 level was substantially increased in colon cancer tissues and was obviously correlated with the tumor volume and early distant metastasis of patients. Besides, overexpression of LBX2-AS1 remarkably boosted growth, proliferation, and metastasis and restrained apoptosis in colon cancer cells, whereas LBX2-AS1 knockdown produced the opposite effect. On the other hand, miR-627-5p, down-regulated in colon cancer tissues, was negatively associated with LBX2-AS1 expression. Functional experiments showed that miR-627-5p suppressed colon cancer growth. Mechanistically, LBX2-AS1, as an endogenous competitive RNA, targeted miR-627-5p and restrained its expression, while miR-627-5p targeted and negatively regulated the RAC1/PI3K/AKT axis. Collectively, this study has revealed that LBX2-AS1 is a poor prognostic factor of colon cancer and can regulate colon cancer progression by regulating the miR-627-5p/RAC1/PI3K/AKT pathway.

Competitive exclusion and coexistence phenomena of a two-strain SIS model on complex networks from global perspectives.

Genetic heterogeneity plays an important role in exploring the interplays of microorganisms. Competitive exclusion principle is the main principle that governs causative agentries of diseases competition. Identifying coexistence mechanisms is a core issue for studying the interactions of multi-strains. In this paper, we are concerned with the dynamics of a two-strain SIS epidemic model with general incidence rate on complex networks. We derive the basic reproduction numbers and the invasion reproduction numbers associated with each strain, which determine the competitive, exclusion and coexistence of the two strains. We strictly prove that the competitive exclusion principle holds in a global sense and the endemic equilibrium coexists uniquely and globally. Numerical examples visibly illustrate the evolution of the two strains.

Optimal control and cost-effective analysis of an age-structured emerging infectious disease model.

Emerging infectious diseases are one of the global public health problems which may lead to widespread epidemics and potentially life-threatening infection. Integrated vaccination and physical distancing interventions are two elementary methods for preventing infectious diseases transmission. In this paper, we construct a continuous age-structured model for investigating the transmission dynamics of an emerging infection disease during a short period. We derive the basic regeneration number R 0 , the spectral radius of the next generation operator K , which determines the disease outbreak or not. Furthermore, we propose an optimal control problem to take account for the cost-effectiveness of social distancing intervention and vaccination. We rigorously obtain sufficient conditions for a L 1 control problem. Numerical simulations show that coupling integrated vaccination and physical distancing intervention could effectively eliminate the infection, and such control strategy is more sensitive for people aged 10-39 and over 60.