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Abstract Background and purpose: Catalpol (CAT) has diverse pharmacological functions, including cellular homeostasis maintenance and anti-inflammatory effects. Sirtuin 5 (SIRT5) plays a considerable role in regulating cellular homeostasis in cardiac diseases. Our research explores the therapeutic potential of CAT against myocardial injury and its underlying mechanism. Methods: The H9c2 cells were pretreated with different CAT concentrations for 24 h, or CAT for 24 h followed by CoCl2 stimulation. Cell viability was determined with MTT assay. Biochemical assays, western blotting, and quantitative real-time PCR (qRT-PCR), combined with bioinformatic analysis, were used to examine the impact of CAT on CoCl2-induced myocardial injury in H9c2 cells and further explore its molecular mechanisms. Results: CAT ameliorated levels of myocardial enzymes, increased nicotinamide adenine dinucleotide (NAD+/NADH) ratio and adenosine triphosphate (ATP), while inhibited lactic acid (LD), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in CoCl2-induced H9c2 cells. Mechanistically, SIRT5 knockdown inhibited Lin28a expression and negated the effects of CAT on ATP level, LD content, and the expression of inflammatory factors in cells. CAT likely exerted its protective effects on myocardial function through the SIRT5-mediated signaling pathway. Conclusions: CAT regulates energy metabolism and inflammation via the SIRT5-mediated signaling pathway, exerting a protective effect in myocardial injury.

Background: The structure of age groups and social contacts of the total population influenced infection scales and hospital-bed requirements, especially influenced severe infections and deaths during the global prevalence of COVID-19. Before the end of the year 2022, Chinese government implemented the national vaccination and had built the herd immunity cross the country, and announced Twenty Measures (November 11) and Ten New Measures (December 7) for further modifications of dynamic zero-COVID polity on the Chinese mainland. With the nation-wide vaccination and modified measures background, Fuzhou COVID-19 large wave (November 19, 2022–February 9, 2023) led by Omicron BA.5.2 variant was recorded and prevailed for three months in Fujian Province. Methods: A multi-age groups susceptible-exposed-infected-hospitalized-recovered (SEIHR) COVID-19 model with social contacts was proposed in this study. The main object was to evaluate the impacts of age groups and social contacts of the total population. The idea of Least Squares method was governed to perform the data fittings of four age groups against the surveillance data from Fujian Provincial Center for Disease Control and Prevention (Fujian CDC). The next generation matrix method was used to compute basic reproduction number for the total population and for the specific age group. The tendencies of effective reproduction number of four age groups were plotted by using the Epiestim R package and the SEIHR model for in-depth discussions. The sensitivity analysis by using sensitivity index and partial rank correlation coefficients values (PRCC values) were operated to reveal the differences of age groups against the main parameters. Results: The main epidemiological features such as basic reproduction number, effective reproduction number and sensitivity analysis were extensively discussed for multi-age groups SEIHR model in this study. Firstly, by using of the next generation matrix method, basic reproduction number R0 of the total population was estimated as 1.57 using parameter values of four age groups of Fuzhou COVID-19 large wave. Given age group k, the values of R0k (age group k to age group k), the values of R0k (an infected of age group k to the total population) and the values of R^0k (an infected of the total population to age group k) were also estimated, in which the explorations of the impacts of age groups revealed that the relationship R0k>R0k>R^0k was valid. Then, the fluctuating tendencies of effective reproduction number Rt were demonstrated by using two approaches (the surveillance data and the SEIHR model) for Fuzhou COVID-19 large wave, during which high-risk group (G4 group) mainly contributed the infection scale due to high susceptibility to infection and high risks to basic diseases. Further, the sensitivity analysis using two approaches (the sensitivity index and the PRCC values) revealed that susceptibility to infection of age groups played the vital roles, while the numerical simulation showed that infection scale varied with the changes of social contacts of age groups. The results of this study claimed that the high-risk group out of the total population was concerned by the local government with the highest susceptibility to infection against COVID-19. Conclusions: This study verified that the partition structure of age groups of the total population, the susceptibility to infection of age groups, the social contacts among age groups were the important contributors of infection scale. The less social contacts and adequate hospital beds for high-risk group were profitable to control the spread of COVID-19. To avoid the emergence of medical runs against new variant in the future, the policymakers from local government were suggested to decline social contacts when hospital beds were limited.

Organ transplantation is the optimal treatment for patients with end-stage organ failure, but which faces the challenge of donor shortage. Two-dimensional cell culture and animal experiments are difficult to completely simulate the complex cellular microenvironment for drug testing. Three-dimensional (3D) bioprinting is an emerging manufacturing technology to fabricate artificial tissues and organs for transplantation and drug screening. This review first describes the bioprinting technologies used to fabricate constructs, including jetting-based, extrusion-based, vat photopolymerization-based methods and other emerging 3D bioprinting approaches. The various kinds of bioinks, cell sources, and the most recent applications of 3D bioprinting tissues and organs in transplantation and drug testing are subsequently summarized. Finally, we discuss the challenges and prospects of 3D bioprinting of tissues and organs. This review aims to facilitate the overcoming of the obstacles identified on the challenging journey towards the manufacturing and adoption of tissue and organs in transplantation and drug screening.

The epidemiological characteristics and distributions of two epidemics in Fujian Province of Southeast China were attributed to the complex interactions among variant, host, and non-pharmaceutical interventions (NPIs). All reported cases in the Putian epidemic (September 8–October 2, 2021, Delta variant B.1.617.2) and Fuzhou epidemic (October 22–November 18, 2022, Omicron variant BA.5.2) were classified by sex, age group, occupation, and location in this study. Using surveillance data from the Fujian Provincial Center for Disease Control and Prevention, we established a virus-oriented SVEIR (Susceptible–Vaccinated–Exposed–Infected–Recovered) model to investigate the dynamic evolution features of these two variants and the effects of NPIs. The optimal simulations were carried out with variants and scenario investigations. The scenario investigations showed that NPIs significantly reduced the transmission risk and infection scales of COVID-19, and that the Omicron variant was more infectious than the Delta variant. Moreover, the dynamic investigations revealed the increasing tendencies from Delta to Omicron, such as the basic reproduction number, infection rate, percentage of high-risk cases, and the growth rate. Decreasing tendencies were also identified, such as the average recovery period, the awareness delay, and the percentage of symptomatic cases. This study highlighted that NPIs played critical roles in successfully containing the two epidemics. Such interventions are strongly recommended to public health policymakers.

Objective To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity. Methods Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types. Results A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215–48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126– 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966–9.727; p < 0.001) was confirmed as an independent risk factor for IONM events. Conclusion We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.

In this paper, we analyze the global asymptotic behaviors of a mathematical susceptible-infected(SI) age-infection-structured human immunodeficiency virus(HIV) model with heterogeneous transmission. Mathematical analysis shows that the local and global dynamics are completely determined by the basic reproductive number R0. If R01, it shows that disease-free equilibrium is unstable and the unique endemic equilibrium is globally asymptotically stable. The proofs of global stability utilize Lyapunov functions. Besides, the numerical simulations are illustrated to support these theoretical results and sensitivity analysis of each parameter for R0 is performed by the method of partial rank correlation coefficient(PRCC).

To effectively combat emerging infectious diseases like COVID-19, it is crucial to adopt strict prevention and control measures promptly to effectively contain the spread of the epidemic. In this paper, we propose a transmission model to investigate the influence of two control strategies: reducing contact numbers and improving medical resources. We examine these strategies in terms of constant control and time-varying control. Through sensitivity analysis on two reproduction numbers of the model with constant control, we demonstrate that reducing contact numbers is more effective than improving medical resources. Furthermore, these two constant controls significantly influence the peak values and timing of infections. Specifically, intensifying control measures can reduce peak values, albeit at the expense of delaying the peak time. In the model with time-varying control, we initially explore the corresponding optimal control problem and derive the characteristic expression of optimal control. Subsequently, we utilize real data from January 10th to April 12th, 2020, in Wuhan city as a case study to perform parameter estimation by using our proposed improved algorithm. Our findings illustrate that implementing optimal control measures can effectively reduce infections and deaths, and shorten the duration of the epidemic. Then, we numerically explore that implementing control measures promptly and increasing intensity to reduce contact numbers can make actual control be more closer to optimized control. Finally, we utilize the real data from October 31st to November 18th, 2021, in Hebei province as a second case study to validate the feasibility of our proposed suggestions.

Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.

In the Chinese cultural context, the collaborative interaction characteristics among three key entities - families, kindergartens, and communities - and the mechanisms of their correlation with preschool children’s social behavior problems have not been fully understood yet. Based on ecological systems Theory and social support theory, this study aimed to examine the correlation between parent-teacher relationships and preschool children’s social behavior problems in Chinese kindergartens, as well as the mediating role of parents’ work–family conflict and parenting self-efficacy. Structural equation modeling was used to test the research hypotheses based on a questionnaire survey of 1,784 parents of preschool children. The main findings of this study are as follows: (1) Parents’ perceived positive parent-teacher relationships are negatively correlated with preschool children’s social problems. (2) Parents’ work–family conflict and parenting self-efficacy mediate the relationship between parent-teacher relationships and preschool children’s social behavior problems; (3) Parents’ work–family conflict and parenting self-efficacy play a chain mediating role in the influence of the parent-teacher relationship on preschool children’s social behavior problems. Taken together, the results collectively further elucidate the correlation between parent-teacher relationships and preschool children’s social behavior problems, while also discussing other relevant factors pertaining to children’s social behavior problems. Theoretically, this study expands the understanding of how external environmental resources interact with home and family education. Practically, this research indicates that governments, early childhood education institutions, and workplaces need to strengthen their support for family education of preschool children. The findings contribute to promoting a multi-faceted co-operation aimed at enhancing the quality of early childhood education and fostering the social adaptability and holistic development of preschool children.

Abstract Protein synthesis is frequently deregulated during tumorigenesis. However, the precise contexts of selective translational control and the regulators of such mechanisms in cancer is poorly understood. Here, we uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia. Elevated CNOT3 expression correlates with unfavorable outcomes in patients with acute myeloid leukemia (AML). CNOT3 depletion induces differentiation and apoptosis and delayed leukemogenesis. Transcriptomic and proteomic profiling uncovers c-MYC as a critical downstream target which is translationally regulated by CNOT3. Global analysis of mRNA features demonstrates that CNOT3 selectively influences expression of target genes in a codon usage dependent manner. Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.

The tumor microenvironment responsive multifunctional nanoplatforms with integrated diagnosis and therapy have recently received great attention in anti-cancer treatment. In this study, we developed biocompatible iron oxide-hydroxide-based nanorods (DOX-FPT NRs) for MR imaging and H2S scavenging assisted synergistic photothermal-chemotherapy of colon cancer, which is fabricated by modifying polydopamine (PDA) and transferrin (Tf) on the surface of iron oxide hydroxide (FeOOH) nanorods. The prepared DOX-FPT NRs could precisely target the colon cancer cells through transferrin ligand-receptor-mediated targeting and effectively scavenge endogenous H2S to prohibit the growth of colon cancer. Meanwhile, the considerable drug loading capability and outstanding photothermal conversion efficiency are permitted by the PDA shell modification. In addition, the H2S scavenging assisted photothermal-chemotherapy showed an excellent therapeutic effect on CT26 cells via in vitro cell test. Therefore, the prepared DOX-PFT NRs will be a promising nanoplatform to enhance the therapeutic effect of colon cancer through the treatment strategy of H2S scavenging-assisted synergistic photothermal chemotherapy.

Tuberculosis and COVID-19 co-infection is currently the major issue of public health in many nations, including Ghana. Therefore, to explore the effects of the two Tuberculosis strains on COVID-19, we suggest a Tuberculosis and COVID-19 co-infection model. The study also provides the most economical and effective control methods to reduce the co-infection of tuberculosis and COVID-19. Based on the behavioral patterns of the two Tuberculosis strains and COVID-19 reproduction numbers, the stability of the co-infection model is examined. We explore the sensitivity of the parameters to examine the effect of the drug-resistant and drug-sensitive strain of Tuberculosis on the co-infection of COVID-19. We determine the most cost-effective and optimal treatment strategies that aim to maximize outcomes while minimizing tuberculosis and/or COVID-19 incidences, cost-effectiveness, and optimization approaches. The outcomes of this work contribute to a better understanding of Tuberculosis and COVID-19 epidemiology and provide insights into implementing interventions needed to minimize Tuberculosis and COVID-19 burden in similar settings worldwide.

The spread and control of coronavirus disease 2019 (COVID-19) present a worldwide economic and medical burden to public health. It is imperative to probe the effect of vaccination and infectivity reductions in minimizing the impact of COVID-19. Therefore, we analyze a mathematical model incorporating different infectivity reductions. This work provides the most economical and effective control methods for reducing the impact of COVID-19. Using data from Ghana as a sample size, we study the sensitivity of the parameters to estimate the contributions of the transmission routes to the effective reproduction number Re. We also devise optimal interventions with cost–benefit analysis that aim to maximize outcomes while minimizing COVID-19 incidences by deploying cost-effectiveness and optimization techniques. The outcomes of this work contribute to a better understanding of COVID-19 epidemiology and provide insights into implementing interventions needed to minimize the COVID-19 burden in similar settings worldwide.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

A vector–host model of dengue with multiple stages and independent fluctuations is investigated in this paper. Firstly, the existence and uniqueness of the positive solution are shown by contradiction. When the death rates of aquatic mosquitoes, adult mosquitoes, and human beings respectively control the intensities of white noises, and if R0s>1, then the persistence in the mean for both infective mosquitoes and infective human beings is derived. When R0s>1 is valid, the existence of stationary distribution is derived through constructing several appropriate Lyapunov functions. If the intensities of white noises are controlled and φ<0 is valid, then the extinction for both infective mosquitoes and infective human beings is obtained by applying the comparison theorem and ergodic theorem. Further, the main findings are verified through numerical simulations by using the positive preserving truncated Euler–Maruyama method (PPTEM). Moreover, several numerical simulations on the infection scale of dengue in Fuzhou City were conducted using surveillance data. The main results indicate that the decrease in the transfer proportion from aquatic mosquitoes to adult mosquitoes reduces the infection scale of infective human beings with dengue virus, and the death rates of aquatic mosquitoes and adult mosquitoes affect the value of the critical threshold R0s. Further, the controls of the death rates of mosquitoes are the effective routes by the decision-makers of the Chinese mainland against the spread of dengue.

Strangles is one of the most prevalent horse diseases globally. The infected horses may be asymptomatic and can still carry the infectious pathogen after it recovers, which are named asymptomatic infected horses and long-term subclinical carriers, respectively. Based on these horses, this paper establishes a dynamical model to screen, measure, and model the spread of strangles. The basic reproduction number $ \mathcal{R}_0 $ is computed through a next generation matrix method. By constructing Lyapunov functions, we concluded that the disease-free equilibrium is globally asymptotically stable if $ \mathcal{R}_0 < 1 $, and the endemic equilibrium exits uniquely and is globally asymptotically stable if $ \mathcal{R}_0 > 1 $. For example, while studying a strangles outbreak of a horse farm in England in 2012, we computed an $ \mathcal{R}_0 = 0.8416 $ of this outbreak by data fitting. We further conducted a parameter sensitivity analysis of $ \mathcal{R}_0 $ and the final size by numerical simulations. The results show that the asymptomatic horses mainly influence the final size of this outbreak and that long-term carriers are connected to an increased recurrence of strangles. Moreover, in terms of the three control measures implemented to control strangles(i.e., vaccination, implementing screening regularly and isolating symptomatic horses), the result shows that screening is the most effective measurement, followed by vaccination and isolation, which can provide effective guidance for horse management.

Although microgravity has been implicated in osteoporosis, the precise molecular mechanism remains elusive. Here, we found that microgravity might induce mitochondrial protein buildup in skeletal muscle, alongside reduced levels of LONP1 protein. We revealed that disruptions in mitochondrial proteolysis, induced by the targeted skeletal muscle-specific deletion of the essential mitochondrial protease LONP1 or by the acute inducible deletion of muscle LONP1 in adult mice, cause reduced bone mass and compromised mechanical function. Moreover, the bone loss and weakness phenotypes were recapitulated in skeletal muscle-specific overexpressing ΔOTC mice, a known protein degraded by LONP1. Mechanistically, mitochondrial proteostasis imbalance triggered the mitochondrial unfolded protein response (UPRmt) in muscle, leading to an up-regulation of multiple myokines, including FGF21, which acts as a pro-osteoclastogenic factor. Surprisingly, this mitochondrial proteostasis stress influenced muscle–bone crosstalk independently of ATF4 in skeletal muscle. Furthermore, we established a marked association between serum FGF21 levels and bone health in humans. These findings emphasize the pivotal role of skeletal muscle mitochondrial proteostasis in responding to alterations in loading conditions and in coordinating UPRmt to modulate bone metabolism.

The differences of SARS-CoV-2 variants brought the changes of transmission characteristics and clinical manifestations during the prevalence of COVID-19. In order to explore the evolution mechanisms of SARS-CoV-2 variants and the impacts of variant evolution, the classic SIR (Susceptible-Infected-Recovered) compartment model was modified to a generalized SVEIR (Susceptible-Vaccinated-Exposed-Infected-Recovered) compartment model with age-group and varying variants in this study. By using of the SVEIR model and least squares method, the optimal fittings against the surveillance data from Fujian Provincial Center for Disease Control and Prevention were performed for the five epidemics of Fujian Province. The main epidemiological characteristics such as basic reproduction number, effective reproduction number, sensitivity analysis, and cross-variant scenario investigations were extensively investigated during dynamic zero-COVID policy. The study results showed that the infectivities of the variants became fast from wild strain to the Delta variant, further to the Omicron variant. Meanwhile, the cross-variant investigations showed that the average incubation periods were shortened, and that the infection scales quickly enhanced. Further, the risk estimations with the new variants were performed without implements of the non-pharmaceutical interventions, based on the dominant variants XBB.1.9.1 and EG.5. The results of the risk estimations suggested that non-pharmaceutical interventions were necessary on the Chinese mainland for controlling severe infections and deaths, and also that the regular variant monitors were still workable against the aggressive variant evolution and the emergency of new transmission risks in the future.

Human-to-human contact plays a leading role in the transmission of infectious diseases, and the contact pattern between individuals has an important influence on the intensity and trend of disease transmission. In this paper, we define regular contacts and random contacts. Then, taking the COVID-19 outbreak in Yangzhou City, China as an example, we consider age heterogeneity, household structure and two contact patterns to establish discrete dynamic models with switching between daytime and nighttime to depict the transmission mechanism of COVID-19 in population. We studied the changes in the reproduction number with different age groups and household sizes at different stages. The effects of the proportion of two contacts patterns on reproduction number were also studied. Furthermore, taking the final size, the peak value of infected individuals in community and the peak value of quarantine infected individuals and nucleic acid test positive individuals as indicators, we evaluate the impact of the number of random contacts, the duration of the free transmission stage and summer vacation on the spread of the disease. The results show that a series of prevention and control measures taken by the Chinese government in response to the epidemic situation are reasonable and effective, and the young and middle-aged adults (aged 18-59) with household size of 6 have the strongest transmission ability. In addition, the results also indicate that increasing the proportion of random contact is beneficial to the control of the infectious disease in the phase with interventions. This work enriches the content of infectious disease modeling and provides theoretical guidance for the prevention and control of follow-up major infectious diseases.

A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (–1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy −7.50 kcal/mol).

Rabies is an acute zoonotic infectious disease caused by rabies virus. In 2015, the World Health Organization proposed the goal of eliminating dog-induced human rabies by 2030. In response to this goal positively, China has been dedicated to the control and elimination of rabies mainly caused by dogs, for nearly 10 years. By applying infectious disease dynamics, in this paper, we establish a dog-human rabies transmission model to forecast future epidemic trends of rabies, assess whether the goal of eliminating dog-induced human rabies cases in China can be achieved in 2030, and further evaluate and suggest the follow-up sustained preventive measures after the elimination of human rabies. By analyzing and simulating above dynamic model, it is concluded that rabies has been well controlled in China in recent years, but dog-induced human rabies cannot be eliminated by 2030 according to current situation. In addition, we propose to improve rabies control efforts by increasing the immunization coverage rate of rural domestic dogs, controlling the number of stray dogs and preventing the import of rabies virus in wild animals. Immunization coverage rate of rural domestic dogs which is currently less than 10% is far from requirement, and it needs to reach 50%–60% to meet the goal of 2030. Since it is difficult to immunize stray dogs, we suggest to control the number of stray dogs below 15.27 million to achieve the goal. If the goal of eliminating human rabies is reached in 2030, the essential immunization coverage needs to be maintained for 18 years to reduce the number of canine rabies cases to zero. Lastly, to prevent transmission of rabies virus from wild animals to dogs, the thresholds of the number of dogs and the immunization coverage rate of dogs after eliminating canine rabies cases are also discussed.

ABSTRACTA multi-patch HIV/AIDS model with heterosexual transmission is formulated to investigate the impact of population migration on the spread of HIV/AIDS. We derive the basic reproduction number [Formula: see text] and prove that if [Formula: see text], the disease-free equilibrium is globally asymptotically stable. If [Formula: see text] and certain conditions are satisfied, the endemic equilibrium is globally asymptotically stable. We apply the model to two patches and conduct numerical simulations. If HIV/AIDS becomes extinct in each patch when two patches are isolated, the disease remains extinct in two patches when the population migration occurs; if HIV/AIDS spreads in each patch when two patches are isolated, the disease remains persistent in two patches when the population migration occurs; if the disease disappears in one patch and spreads in the other patch when they are isolated, the disease can spread or disappear in two patches if migration rates of individuals are suitably chosen.

Dengue is one of the most infectious diseases in the world. In Bangladesh, dengue occurs nationally and has been endemic for more than a decade. Therefore, it is crucial that we model dengue transmission in order to better understand how the illness behaves. This paper presents and analyzes a novel fractional model for the dengue transmission utilizing the non-integer Caputo derivative (CD) and are analysed using q-homotopy analysis transform method (q-HATM). By using the next generation method, we derive the fundamental reproduction number $ R_0 $ and show the findings based on it. The global stability of the endemic equilibrium (EE) and the disease-free equilibrium (DFE) is calculated using the Lyapunov function. For the proposed fractional model, numerical simulations and dynamical attitude are seen. Moreover, A sensitivity analysis of the model is performed to determine the relative importance of the model parameters to the transmission.

The prediction system EpiSIX was used to study the COVID-19 epidemic in mainland China between November 2022 and January 2023, based on reported data from December 9, 2022, to January 30, 2023, released by The Chinese Center for Disease Control and Prevention on February 1, 2023. Three kinds of reported data were used for model fitting: the daily numbers of positive nucleic acid tests and deaths, and the daily number of hospital beds taken by COVID-19 patients. It was estimated that the overall infection rate was 87.54% and the overall case fatality rate was 0.078%–0.116% (median 0.100%). Assuming that a new COVID-19 epidemic outbreak would start in March or April of 2023, induced by a slightly more infectious mutant strain, we predicted a possible large rebound between September and October 2023, with a peak demand of between 800,000 and 900,000 inpatient beds. If no such new outbreak was induced by other variants, then the current COVID-19 epidemic course in mainland China would remain under control until the end of 2023. However, it is suggested that the necessary medical resources be prepared to manage possible COVID-19 epidemic emergencies in the near future, especially for the period between September and October 2023.

In this study, we propose a Caputo-based fractional compartmental model for the dynamics of the novel COVID-19. The dynamical attitude and numerical simulations of the proposed fractional model are observed. We find the basic reproduction number using the next-generation matrix. The existence and uniqueness of the solutions of the model are investigated. Furthermore, we analyze the stability of the model in the context of Ulam-Hyers stability criteria. The effective numerical scheme called the fractional Euler method has been employed to analyze the approximate solution and dynamical behavior of the model under consideration. Finally, numerical simulations show that we obtain an effective combination of theoretical and numerical results. The numerical results indicate that the infected curve predicted by this model is in good agreement with the real data of COVID-19 cases.

Abstract Background The ongoing coronavirus 2019 (COVID-19) pandemic has emerged and caused multiple pandemic waves in the following six countries: India, Indonesia, Nepal, Malaysia, Bangladesh and Myanmar. Some of the countries have been much less studied in this devastating pandemic. This study aims to assess the impact of the Omicron variant in these six countries and estimate the infection fatality rate (IFR) and the reproduction number $${R}_{0}$$ R 0 in these six South Asia, Southeast Asia and Oceania countries. Methods We propose a Susceptible-Vaccinated-Exposed-Infectious-Hospitalized-Death-Recovered model with a time-varying transmission rate $$\beta (t)$$ β ( t ) to fit the multiple waves of the COVID-19 pandemic and to estimate the IFR and $${R}_{0}(t)$$ R 0 ( t ) in the aforementioned six countries. The level of immune evasion and the intrinsic transmissibility advantage of the Omicron variant are also considered in this model. Results We fit our model to the reported deaths well. We estimate the IFR (in the range of 0.016 to 0.136%) and the reproduction number $${R}_{0}(t)$$ R 0 ( t ) (in the range of 0 to 9) in the six countries. Multiple pandemic waves in each country were observed in our simulation results. Conclusions The invasion of the Omicron variant caused the new pandemic waves in the six countries. The higher $${R}_{0}(t)$$ R 0 ( t ) suggests the intrinsic transmissibility advantage of the Omicron variant. Our model simulation forecast implies that the Omicron pandemic wave may be mitigated due to the increasing immunized population and vaccine coverage.

The World Health Organization (WHO) declared monkeypox as a public health emergency of international concern (PHEIC) on July 23, 2022, their highest level of alert. This raised concerns about the management of the global monkeypox outbreak, as well as the scientific analysis and accurate prediction of the future course of the epidemic. This study used EpiSIX (an analysis and prediction system for epidemics based on a general SEIR model) to analyze the monkeypox epidemic and to forecast the major tendencies based on data from the USA CDC (https://www.cdc.gov) and the WHO (https://www.who.int/health-topics/monkeypox). The global outbreak of monkeypox started in the UK on May 2, 2022, which marked the beginning of an epidemic wave. As of October 28, 2022, the cumulative number of reported cases worldwide was 77,115, with 36 deaths. EpiSIX simulations predict that the global monkeypox epidemic will enter a low epidemic status on March 1, 2023 with the cumulative number of confirmed cases ranging from 85,000 to 124,000, and the total number of deaths ranging from 60 to 87. Our analysis revealed that the basic reproduction number (R0) of monkeypox virus (MPXV) is near to 3.1 and the percentage of asymptomatic individuals is 13.1 %–14.5 %, both of which are similar to the data for SARS. The vaccination efficiency against susceptibility (VEs) of individuals who have had monkeypox is ∼ 79 %, and the vaccination efficiency against infectiousness (VEi) of individuals who have had monkeypox is ∼ 76 %–82 %. The mean incubation period for monkeypox is 8 days. In total, 94.7 % of infected individuals develop symptoms within 20 days and recover within 2 weeks after the confirmation of symptoms. Simulation results using EpiSIX showed that ring vaccination was remarkably effective against monkeypox. Our findings confirmed that a 20-day isolation for close contacts is necessary.

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The in vitro antibacterial activity of these semisynthetic derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus AD3, and S.aureus 144) were evaluated by the broth dilution method. Compound 13 was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 μg/mL). Furthermore, compound 13 was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound 13 exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound 13 showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 μg/mL. Molecular docking study revealed that compound 13 can effectively bind to the active site of the 50S ribosome (the binding free energy = −9.66 kcal/mol).

Numerous organisations across the globe have significant challenges about corruption, characterised by a systematic, endemic, and pervasive nature that permeates various societal establishments. Hence, we propose the fractional order model of corruption, which encompasses the involvement of corrupt individuals across various stages of education and employment. Specifically, we examine the presence of corruption among children in elementary schools, youths in tertiary institutions, adults in civil services, adults in government and public offices, and individuals who have renounced their involvement in corrupt practices. The basic reproduction number of the system was determined by utilising the next-generation matrix. The strength number was obtained by calculating the second derivative of the corruption-related compartments. The examined model solution’s existence, uniqueness, and stability were established using the Krasnoselski fixed point theorem, the Banach contraction principle, and the Ulam–Hyers theorem, respectively. Based on the numerous figures presented, our simulations indicate a positive correlation between the decline in fractal–fractional order and the increase in the number of individuals susceptible to corruption. This phenomenon results in an increase in the prevalence of corruption among designated sectors of the general population. The persistence of corruption in society is a significant challenge to its eradication, as individuals who see personal gains from engaging in corrupt practices tend to exhibit a recurring inclination towards such behaviour. Nevertheless, it is recommended that to mitigate corruption within various corruption-prone subcategories, there is a need to enhance the level of consciousness and promotion of anti-corruption measures throughout all societal establishments.

African swine fever (ASF) is an acute, hemorrhagic and severe infectious disease caused by the African swine fever virus (ASFV), and leads to a serious threat to the pig industry in China. Yet the impact of the virus in the environment and contaminated swill on the ASFV transmission is unclear in China. Then we build the ASFV transmission model with the virus in the environment and swill. We compute the basic reproduction number, and prove that the disease-free equilibrium is globally asymptotically stable when $ R_0 < 1 $ and the unique endemic equilibrium is globally asymptotically stable when $ R_0 > 1 $. Using the public information, parameter values are evaluated. PRCCs and eFAST sensitivity analysis reveal that the release rate of ASFV from asymptomatic and symptomatic infectious pigs and the proportion of pig products from infectious pigs to swill have a significant impact on the ASFV transmission. Our findings suggest that the virus in the environment and contaminated swill contribute to the ASFV transmission. Our results may help animal health to prevent and control the ASFV transmission.

In this paper, we consider an age-structured cholera model with saturation incidence, vaccination age of vaccinated individuals, infection age of infected individuals, and biological age of pathogens. First, the basic reproduction number is calculated. When the basic reproduction number is less than one, the disease-free equilibrium is locally stable. Further, the existence of backward bifurcation of the model is obtained. Numerically, we also compared the effects of various control measures, including basic control measures and vaccination, on the number of infected individuals.

Nitrogen (N) and selenium (Se) are beneficial for tea growth and tea quality; however, it is unknown how the combined application of N and Se affects tea quality and N uptake and utilization in tea plants. In the present study, a hydroponic experiment with three N levels (0, 2 and 4.5 mmol/L) and three Se levels (0, 0.3 and 3 mg/L) was carried out with ‘Chuancha No.2’ as the material, and the contents of tea polyphenols, amino acids and caffeine as well as the expression levels of genes related to N uptake and utilization in tea plants were tracked. The findings reveal that the contents of tea polyphenols, AAs and caffeine in new shoots were the highest when supplied with 0.3 mg/L Se and 4.5 mmol/L N, while the contents of total N, AAs and tea polyphenols in mature leaves were the highest at the concentrations of 3 mg/L Se and 2 mmol/L N. Se supply (0.3 and 3 mg/L) induced an increase in amino acid and tea polyphenol contents in tea shoots under N deficiency conditions, whereas total N content, tea polyphenols and AAs in mature leaves and total N content in tea roots decreased significantly. When supplied with N (2 mmol/L and 4.5 mmol/L), the contents of tea polyphenols and caffeine in new shoots first increased and then decreased with the increase in Se concentration, while the total N content in mature leaves and roots increased. In leaves, CsAMT1.1, CsAMT1.2 and CsAMT3.1 had similar trends, and their expression levels were remarkably upregulated when supplied with 0.3 mg/L Se or 2 mmol/L N, respectively; the expression level of CsGS1.1 was significantly induced by N and Se, while CsGS1.2 and CsTS1 were mainly induced by N. In roots, CsAMT1.1 could play a major role in N uptake under the combined application of N and Se; CsGS1.2 expression was significantly induced compared to CsGS1.1 under the combined application of N and Se. This study explored the potential of the interaction of Se and N to promote tea quality and N uptake and utilization in tea plants.

Following a stroke, the emergence of amygdala-related disorders poses a significant challenge, with severe implications for post-stroke mental health, including conditions such as anxiety and depression. These disorders not only hinder post-stroke recovery but also elevate mortality rates. Despite their profound impact, the precise origins of aberrant amygdala function after a stroke remain elusive. As a target of reduced brain pH in ischemia, acid-sensing ion channels (ASICs) have been implicated in synaptic transmission after ischemia, hinting at their potential role in reshaping neural circuits following a stroke. This study delves into the intriguing relationship between post-stroke alterations and ASICs, specifically focusing on postsynaptic ASIC1a enhancement in the amygdala following prefrontal cortex (PFC) ischemia induced by endothelin-1 (ET-1) injection. Our findings intriguingly illustrate that mPFC ischemia not only accentuates the PFC to the amygdala circuit but also implicates ASIC1a in fostering augmented synaptic plasticity after ischemia. In contrast, the absence of ASIC1a impairs the heightened induction of long-term potentiation (LTP) in the amygdala induced by ischemia. This pivotal research introduces a novel concept with the potential to inaugurate an entirely new avenue of inquiry, thereby significantly enhancing our comprehension of the intricate mechanisms underlying post-stroke neural circuit reconfiguration. Importantly, these revelations hold the promise of paving the way for groundbreaking therapeutic interventions.

Abstract Histone deacetylase 11 (HDAC11), a sole member of the class IV HDAC subfamily, participates in various cardiovascular diseases. Recent evidence showed that pyroptosis was a form of inflammatory programmed cell death and is critical for atherosclerosis (AS). However, little is known about the effect of HDAC11 on endothelial cell pyroptosis in AS. Thus, this study aims to investigate the role of HDAC11 in vascular endothelial cell pyroptosis and its molecular mechanism. Firstly, we found that HDAC11 expression was up-regulated and pyroptosis occurred in the aorta of ApoE−/− mice fed with a high-fat diet (HFD) for 8 or 12 weeks. Then, in vitro study found the treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α) resulted in pyroptosis, as evidenced by activation of caspase-1 and caspase-3 activation, cleavage of downstream gasdermin D (GSDMD) and gasdermin E (GSDME/DFNA5), the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-18, as well as elevation of LDH activity and increase of propidium iodide (PI)-positive cells. Besides, TNF-α increased HDAC11 expression and induced pyroptosis via TNFR1 in HUVECs. HDAC11 knockdown mitigated pyroptosis by suppressing both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways in TNF-α-induced HUVECs. Moreover, GSDME knockdown by siRNA significantly decreased pyroptosis and inflammatory response, while treatment with disulfiram or necrosulfonamide (NSA) further augmented the inhibitory effects of GSDME siRNA on pyroptosis and inflammatory response. Further studies found HDAC11 formed a complex with ERG and decreased the acetylation levels of ERG. More importantly, ERG knockdown augmented vascular endothelial cell pyroptosis in TNF-α-induced HUVECs. Taken together, our study suggests that HDAC11 might promote both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways leading to pyroptosis via regulation of ERG acetylation in HUVECs. Modulation of HDAC11 may serve as a potential target for therapeutic strategies of AS.

Classical epidemiological models assume mass action. However, this assumption is violated when interactions are not random. With the recent COVID-19 pandemic, and resulting shelter in place social distancing directives, mass action models must be modified to account for limited social interactions. In this paper we apply a pairwise network model with moment closure to study the early transmission of COVID-19 in New York and San Francisco and to investigate the factors determining the severity and duration of outbreak in these two cities. In particular, we consider the role of population density, transmission rates and social distancing on the disease dynamics and outcomes. Sensitivity analysis shows that there is a strongly negative correlation between the clustering coefficient in the pairwise model and the basic reproduction number and the effective reproduction number. The shelter in place policy makes the clustering coefficient increase thereby reducing the basic reproduction number and the effective reproduction number. By switching population densities in New York and San Francisco we demonstrate how the outbreak would progress if New York had the same density as San Francisco and vice-versa. The results underscore the crucial role that population density has in the epidemic outcomes. We also show that under the assumption of no further changes in policy or transmission dynamics not lifting the shelter in place policy would have little effect on final outbreak size in New York, but would reduce the final size in San Francisco by 97%.

Abstract Foot-and-mouth disease (FMD) is an acute, highly infectious and pathogenic animal disease. In recent years, with the rapid development of the swine breeding industry in China, pig farms have shown a trend of larger-scale development. Large-scale pig farms employ standardized management, a high level of automation, and a strict system. However, these farms have a large trading volume, and increased transmission intensity of FMD is noted inside the farm. At present, the main control measure against FMD is pig vaccination. However, a standard for immunization procedures is not available, and currently adopted immunization procedures have not been effectively and systematically evaluated. Taking a typical large-scale pig farm in China as the research subject and considering the breeding pattern, piggery structure, age structure and immunization procedures, an individual-based state probability model is established to evaluate the effectiveness of the immune procedure. Based on numerical simulation, it is concluded that the optimal immunization program involves primary immunization at 40 days of age and secondary immunization at 80 days of age for commercial pigs. Breeding boars and breeding sows are immunized 4 times a year, and reserve pigs are immunized at 169 and 259 days of age. According to the theoretical analysis, the average control reproduction number of individuals under the optimal immunization procedure in the farm is 0.4927. In the absence of immunization, the average is 1.7498, indicating that the epidemic cannot be controlled without immunization procedures.

Patch models can better reflect the impact of spatial heterogeneity and population mobility on disease transmission. While, there is relatively little work on using patch models to study the role of travel restrictions, contact tracing and vaccination in COVID-19 epidemic. In this paper, based on COVID-19 epidemic propagation and diffusion mechanism, we establish a dynamic model of disease spread among two patches in which Wuhan is regarded as one patch and the rest of Mainland China (outside Wuhan) as the other patch. The existence of the final size is proved theoretically and some model parameters are estimated by using the reported confirmed cases. The results show that travel restrictions greatly reduce the number of confirmed cases in Mainland China, and the earlier enforced, the fewer confirmed cases. However, it is impossible to bring the COVID-19 epidemic under control and lift travel restrictions on April 8, 2020 by imposing travel restrictions alone, the same is true for contact tracing. While, the disease can always be controlled if the protection rate of herd immunity is high enough and the corresponding critical threshold is given. Therefore, in order to quickly control the spread of the emerging infectious disease (such as COVID-19), it is necessary to combine a variety of control measures and develop vaccines and therapeutic drugs as soon as possible.

Abstract Endometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remains unclear. Hence, this study investigated the effect of iron overload on mouse embryos and elucidated the molecular mechanism. Iron overload in endometriosis PF disrupted blastocyst formation, decreased GPX4 expression and induced lipid peroxidation, suggesting that iron overload causes embryotoxicity and induces ferroptosis. Moreover, mitochondrial damage occurs in iron overload-treated embryos, presenting as decreased ATP levels, increased ROS levels and MMP hyperpolarization. The cytotoxicity of iron overload is attenuated by the ferroptosis inhibitor Fer-1. Furthermore, Smart-seq analysis revealed that HMOX1 is upregulated in embryo ferroptosis and that HMOX1 suppresses ferroptosis by maintaining mitochondrial function. This study provides new insight into the mechanism of endometriosis infertility and a potential target for future endometriosis infertility treatment efforts.

Abstract This study proposes a method to reduce the electromagnetic noise of a double‐layer interior permanent magnet synchronous motor (DIPMSM) by optimising the flux barrier. First, a noise prediction model of the 36‐slot/8‐pole DIPMSM is established by finite element (FE). According to the simulation results, the noise of the motor is the loudest at 5000 rpm, especially with a noise component of 3333.3 Hz. From the results of modal analysis, it can be concluded that the four‐order radial force with a frequency of 3333.3 Hz resonates with the stator, resulting in the loudest noise. Then, the source of the radial force that causes the loudest noise is analysed, and it can be found that the 9th and 11th harmonics of rotor magnetic motive force have the greatest contribution to the force. By optimising the rotor, the radial force contributed by the 9th and 11th harmonics is weakened, thereby reducing the noise caused by these harmonics. Finally, the electromagnetic performance and noise of the optimised motor are checked by FE. Compared with the initial rotor, the torque ripple is reduced by 26.79%, and noise is reduced by 5.542 dB. The noise test on the prototype verifies the accuracy of the noise prediction model.

Abstract Influenza is an infectious disease with obvious periodic changes over time. It is of great practical significance to explore the non-environment-related factors that cause this regularity for influenza control and individual protection. In this paper, based on the randomness of population number and the heterogeneity of population contact, we have established a stochastic infectious disease model about influenza based on the degree of the network, and obtained the power spectral density function by using the van Kampen expansion method of the master equation. The relevant parameters are obtained by fitting the influenza data of sentinel hospitals. The results of the numerical analysis show that: (1) for the infected, the infection period of patients who go to the sentinel hospitals is particularly different from the others who do not; (2) for all the infected, there is an obvious nonlinear relationship between their infection period and the visiting rate of the influenza sentinel hospitals, the infection rate and the degree. Among them, only the infection period of patients who do not go to the sentinel hospitals decreased monotonously with the infection rate (increased monotonously with the visiting rate), while the rest had a non-monotonic relationship.

The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with IVF-ET outcomes. A total of 216 subjects aged

COVID-19 pandemic remains serious around the world and causes huge deaths and economic losses. To investigate the effect of vaccination and isolation delays on the transmission of COVID-19, we propose a mathematical model of COVID-19 transmission with vaccination and isolation delays. The basic reproduction number is computed, and the global dynamics of the model are proved. When R01. Based on the public information, parameter values are estimated, and sensitivity analysis is carried out by the partial rank correlation coefficients (PRCCs) and the extended version of the Fourier amplitude sensitivity test (eFAST). Our results suggest that the isolation rates of asymptomatic and symptomatic infectious individuals have a significant impact on the transmission of COVID-19. When the COVID-19 is epidemic, the optimal control strategies of our model with vaccination and isolation delays are analyzed. Under the limited resource with constant and time-varying isolation rates, we find that the optimal isolation rates may minimize the cumulative number of infected individuals and the cost of disease control, and effectively contain the transmission of COVID-19. Our study may help public health to prevent and control the COVID-19 spread.

Bistability is a ubiquitous phenomenon in life sciences. In this paper, two kinds of bistable structures in two-dimensional dynamical systems are studied: one is two one-point attractors, another is a one-point attractor accompanied by a cycle attractor. By the Conley index theory, we prove that there exist other isolated invariant sets besides the two attractors, and also obtain the possible components and their configuration. Moreover, we find that there is always a separatrix or cycle separatrix, which separates the two attractors. Finally, the biological meanings and implications of these structures are given and discussed.

Pork makes up the highest proportion of household expenditure on meat in China and supply and demand have been basically stable in the past decade. However, the catastrophic outbreak of African swine fever (ASF) in August 2018 disrupted the balance and reduced the national herd by half within six months. The consequence was a gross lack of supply to the market and consumer demand was unable to be met. Accordingly, live pig prices rose sharply from 2019. In order to assess the influence of ASF on the price of the live pigs, we use a price function to characterize the relationship between price of the live pigs and the nation's pig stock, and then establish a time delay ASF epidemic dynamical model with the price function. By analyzing the dynamical behaviors of the model, we calculate the basic reproductive number, discuss the stability of equilibrium, and obtain the critical conditions for Hopf bifurcation. The model reasonableness is confirmed by carrying out data fitting and parameter estimation based on price data of the live pigs, the pig stock data and the outbreak data of ASF. By performing sensitivity analysis, we intuitively show the impact of ASF on the price of live pigs and the pig stocks, and assess the key factors affecting the outbreak of ASF. The conclusion is drawn that, with the control measures adopted by related government department in China, the basic reproductive number ($ R_0 = 0.6005 $) means that the ASF epidemic has been controlled. Moreover, the price of the live pig increases linearly with $ R_0 $, while the effect of the number of infected pigs on the subsequent price is non-linear related. Our findings suggest that society and the government should pay more attention to the prevention of animal disease epidemics.

In this paper, we investigate a reaction-diffusive-advection two-species competition model with one delay and Dirichlet boundary conditions. The existence and multiplicity of spatially non-homogeneous steady-state solutions are obtained. The stability of spatially nonhomogeneous steady-state solutions and the existence of Hopf bifurcation with the changes of the time delay are obtained by analyzing the distribution of eigenvalues of the infinitesimal generator associated with the linearized system. By the normal form theory and the center manifold reduction, the stability and bifurcation direction of Hopf bifurcating periodic orbits are derived. Finally, numerical simulations are given to illustrate the theoretical results.

Abstract Background Laser-assisted hatching (LAH) has been widely applied to facilitate blastocyst hatching in IVF-ET treatment, however, the effect of LAH on subsequent development and clinical outcomes of the lower grade cleavage stage embryos (LGCE) remains unknown. Our study aimed at evaluating the effect of LAH on blastocyst formation and the clinical pregnancy outcomes of LGCE embryos after transfer. Methods A total of 608 cycles of IVF/ICSI treatment from November 2017 to September 2019 were included in our study as follows: 296 in the LAH group and 312 in the N-LAH group. The total blastocyst rate, usable blastocyst rate, good-grade blastocyst rate and clinical pregnancy rate were statistically compared between the two groups. Results The total blastocyst rate (50.7% vs 40.2%, P 0.05, respectively). Conclusions A higher proportion of total blastocysts and usable blastocysts can be obtained by LAH in LGCE, which may be beneficial to the outcome of the IVF/ICSI-ET cycle.

Abstract Dynamin-related protein 1 (Drp1)-mediated mitochondrial dysfunction is associated with synaptic injury in the diabetic brain. However, the dysfunctional mitochondria by Drp1 deletion in the diabetic brain are poorly understood. Here, we investigated the effects of neuron-specific Drp1 deletion on synaptic damage and mitophagy in the hippocampus of a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. HFD/STZ-induced diabetic mice exhibited metabolic disturbances and synaptic damages. Floxed Drp1 mice were crossed with Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-Cre mice, to generate neuron-specific Drp1 knockout (Drp1cKO) mice, which showed marked mitochondrial swelling and dendritic spine loss in hippocampal neurons. In particular, diabetic Drp1cKO mice exhibited an increase in dendritic spine loss and higher levels of oxidative stress and neuroinflammation compared with diabetic wild-type (WT) mice. Diabetic WT mice generally displayed increased Drp1-induced small mitochondrial morphology in hippocampal neurons, but large mitochondria were prominently observed in diabetic Drp1cKO mice. The levels of microtubule-associated protein 1 light-chain 3 and lysosomal-associated membrane protein 1 proteins were significantly increased in the hippocampus of diabetic Drp1cKO mice compared with diabetic WT mice. The inhibition of Drp1 adversely promotes synaptic injury and neurodegeneration in the diabetic brain. The findings suggest that the exploratory mechanisms behind Drp1-mediated mitochondrial dysfunction could provide a possible therapeutic target for diabetic brain complications.

Abstract Reconsolidation has been considered a process in which a consolidated memory is turned into a labile stage. Within the reconsolidation window, the labile memory can be either erased or strengthened. Manipulating acid-sensing ion channels (ASICs) in the amygdala via carbon dioxide (CO2) inhalation enhances memory retrieval and its lability within the reconsolidation window. Moreover, pairing CO2 inhalation with retrieval bears the reactivation of the memory trace and enhances the synaptic exchange of the calcium-impermeable AMPA receptors to calcium-permeable AMPA receptors. Our patch-clamp data suggest that the exchange of the AMPA receptors depends on the ubiquitin-proteasome system (UPS), via protein degradation. Ziram (50 µM), a ubiquitination inhibitor, reduces the turnover of the AMPA receptors. CO2 inhalation with retrieval boosts the ubiquitination without altering the proteasome activity. Several calcium-dependent kinases potentially involved in the CO2-inhalation regulated memory liability were identified using the Kinome assay. These results suggest that the UPS plays a key role in regulating the turnover of AMPA receptors during CO2 inhalation.