Clinical association study on the matrix metalloproteinase expression in the serum of patients with connective tissue disease complicated with interstitial lung disease.

Objectives: This study was implemented to reveal the expression and the clinical correlation of matrix metalloproteinases (MPSs) with connective tissue disease (CTD) complicated with interstitial lung disease (ILD). Patients and methods: This clinical study was conducted with 260 patients (151 males, 109 females; mean age: 47.3±12.5 years; range, 29 to 67 years) between October 2019 and October 2020. Among the subjects, 100 were CTD patients (CTD group), 80 were CTD patients with ILD (CTD-ILD group) and 80 were healthy individuals (control group). The MMP-2, -3, -7, and -9 levels in the serum of the three groups were detected by enzyme-linked immunosorbent assay. Results: Serum levels of MMP-3, -7, and -9 in the CTD-ILD group were higher, while the MMP-2 level was lower than those in the CTD group and the control group. The MMP-7 level in the serum of the CTD-ILD group was positively related to C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor and negatively correlated with immunoglobulin G and complement 3. The MMP-7 expression in the serum was positively correlated with forced expiratory volume in one second (FEV1%), FEV1/forced expiratory volume (FVC), and FVC in CTD-ILD patients. Pearson statistical analysis revealed that there was a significant positive correlation between the MMP-7 expression and the percentage of B cells in the serum of CTD-ILD patients. Conclusion: Expressions of MMP-3, -7, and -9 are significantly increased in the serum of patients with CTD and related interstitial lung lesions, and the high expression of MMP-7 indicates dynamic lung lesions, which is possible to be used as a possible biomarker for early diagnosis and assessment of disease progression.

Effects of Vanadium Microalloying and Intercritical Annealing on Yield Strength-Ductility Trade-Offs of Medium-Manganese Steels.

In this paper, we investigate the effects of vanadium on the strength and ductility of medium-manganese steels by analyzing the microstructural evolution and strain hardening rates and performing quantitative calculations. Two significantly different contents of vanadium, 0.05 and 0.5 wt.%, were independently added to model steel (0.12C-10Mn) and annealed at different intercritical temperatures. The results show that higher vanadium addition increases the yield strength but decreases the ductility. The maximum yield strength can increase from 849 MPa to 1063 MPa at low temperatures. The model calculations reveal that this is due to a precipitation strengthening increment of up to 148 MPa and a dislocation strengthening increment of 50 MPa caused by a higher quantity of V4C3 precipitates. However, the high density of vanadium carbides leads them to easily segregate at grain boundaries or phase interfaces, which prevents strain from uniformly distributing throughout the phases. This results in stress concentrations which cause a high strain hardening rate in the early stages of loading and a delayed transformation-induced plasticity (TRIP) effect. Additionally, the precipitates decrease the austenite proportion and its carbon concentrations, rendering the TRIP effect unsustainable. Accordingly, the ductility of high vanadium steels is relatively low.

Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway.

Ubiquitin D (UBD), a member of the ubiquitin­like modifier family, has been reported to be highly expressed in various types of cancer and its overexpression is positively associated with tumor progression. However, the role and mechanism of UBD in rheumatoid arthritis (RA) remain elusive. In the present study, the gene expression profiles of GSE55457 were downloaded from the Gene Expression Omnibus database to assess differentially expressed genes and perform functional enrichment analyses. UBD was overexpressed by lentivirus transfection. The protein level of UBD, p­p38 and p38 in RA­fibroblast­like synoviocytes (FLSs) were examined by western blotting. Cell Counting Kit­8 and flow cytometry assays were used to detect the functional changes of RA­FLSs transfected with UBD and MAPK inhibitor SB202190. The concentrations of inflammatory factors (IL­2, IL­6, IL­10 and TNF­α) were evaluated using ELISA kits. The results revealed that UBD was overexpressed in RA tissues compared with in the healthy control tissues. Functionally, UBD significantly accelerated the viability and proliferation of RA­FLSs, whereas it inhibited their apoptosis. Furthermore, UBD significantly promoted the secretion of inflammatory factors (IL­2, IL­6, IL­10 and TNF­α). Mechanistically, elevated UBD activated phospohorylated­p38 in RA­FLSs. By contrast, UBD overexpression and treatment with the p38 MAPK inhibitor SB202190 not only partially relieved the UBD­dependent effects on cell viability and proliferation, but also reversed its inhibitory effects on cell apoptosis. Furthermore, SB202190 partially inhibited the effects of UBD overexpression on the enhanced secretion of inflammatory factors. The present study indicated that UBD may mediate the activation of p38 MAPK, thereby facilitating the proliferation of RA­FLSs and ultimately promoting the progression of RA. Therefore, UBD may be considered a potential therapeutic target and a promising prognostic biomarker for RA.

Prevalence and molecular characterization of common thalassemia among people of reproductive age in the border area of Guangxi-Yunnan-Guizhou province in Southwestern China.

Objectives: Thalassemia, the most common global monogenetic disorder, is highly prevalent in southern China. Epidemiological and molecular characterization of thalassemia is important for designing appropriate prevention strategies in high-risk areas, especially the border area of Guangxi-Yunnan-Guizhou province in southwestern China.Methods: We recruited 38812 reproductive age couples and screened them for thalassemia. Routine blood tests as well as hemoglobin components and levels were evaluated. In addition, suspected thalassemia were identified by gap polymerase chain reaction (Gap-PCR) and PCR-based reverse dot blot (PCR-RDB).Results: The overall prevalence of thalassemia was 26.76%. Specifically, incidences of α-thalassemia, ß-thalassemia, and concurrent α- and ß-thalassemia were 17.52%, 6.92%, and 2.32%, respectively. The diagnosed α-thalassemia anomalies were associated with six gene mutations and 25 genotypes. The ß-thalassemia anomalies were associated with 12 gene mutations and 15 genotypes. Moreover, among the 1799 concurrent mutated α- and ß-thalassemia genes, 95 different genotypes were identified. Couples in which both partners were positive for α-thalassemia and ß-thalassemia isotypes were 8.80% and 2.08%, respectively. The proportion of couples at a risk of having children with thalassemia major or intermedia was high.Conclusions: This study elucidates on the prevalence and molecular characterization of thalassemia in the border area of Guangxi-Yunnan-Guizhou provinces. These findings provide valuable baseline data for genetic counseling and prenatal diagnosis, with the overarching goal of preventing and controlling severe thalassemia.

[Study of the genotypic and hematological feature of hemoglobin H disease in West Guangxi area].

OBJECTIVE: To analyze the incidence, genotype and hematological feature of hemoglobin H (HbH) disease in West Guangxi region. METHODS: A total of 1246 patients diagnosed with HbH disease from January 2013 to December 2018 in our hospital were enrolled. Red blood cell parameters, hemoglobin electrophoresis, Gap-polymerase china reaction (Gap-PCR) and polymerase chain reaction-reverse dot blot (PCR-RDB) techniques were used to detect the 6 common α-thalassemia mutations and 17 common ß-thalassemia mutations. The results were compared with those of other regions. RESULTS: The detection rate for HbH disease was 5.66%. Among the 1246 patients, 614 (49.28%) had deletion-type HbH disease, including -α 3.7/--SEA (35.32%),-α 4.2/--SEA(13.72%) and -a 3.7/--THAI(0.24%), 632(50.72%) had non-deleted HbH disease, mainly α CS α /--SEA (44.86%), followed by α WS α/--SEA (4.33%), α QS α /--SEA (1.45%) and α CS α/--THAI(0.08%). Co-committent HbH disease and ß-thalassemia were detected in 54 cases (4.33%). Most patients with HbH disease showed mild to moderate anemia. Very few had severe anemia. Among these, patients with HbH-CS had the most severe anemia, and HbH-WS were the mildest. Hb levels in patients with HbH disease alone were lower than those with co-committent HbH and ß-thalassemia. Compared with other regions, the incidence and genotype of HbH disease of West Guangxi are different. CONCLUSION: The prevalence of HbH disease is high in West Guangxi region, and the main genotypeis non-deletion. α CS α /--SEA is the most common, and most of them had moderate anemia. Compared with the deletion-type HbH disease, non-deleted HbH patients were more severe. When HbH disease co-committed with ß-thalassemia, the severity of anemia is reduced. The difference between West Guangxi and other regions may account for the variance of clinical manifestations and incidence of HbH disease in this region.

The effectiveness of quarantine and isolation determine the trend of the COVID-19 epidemic in the final phase of the current outbreak in China.

OBJECTIVES: Since January 23, 2020, stringent measures for controlling the novel coronavirus epidemic have been gradually enforced and strengthened in mainland China. The detection and diagnosis have been improved, as well. However, the daily reported cases remaining at a high level make the epidemic trend prediction difficult. METHODS: Since the traditional SEIR model does not evaluate the effectiveness of control strategies, a novel model in line with the current epidemic's process and control measures was proposed, utilizing multisource datasets including the cumulative number of reported, deceased, quarantined and suspected cases. RESULTS: Results show that the trend of the epidemic mainly depends on quarantined and suspected cases. The predicted cumulative numbers of quarantined and suspected cases nearly reached static states, and their inflection points have already been achieved, with the epidemic's peak coming soon. The estimated effective reproduction numbers using model-free and model-based methods are decreasing, as well as new infections, while newly reported cases are increasing. Most infected cases have been quarantined or put in the suspected class, which has been ignored in existing models. CONCLUSIONS: The uncertainty analyses reveal that the epidemic is still uncertain, and it is important to continue enhancing the quarantine and isolation strategy and improving the detection rate in mainland China.

The effectiveness of quarantine and isolation determine the trend of the COVID-19 epidemics in the final phase of the current outbreak in China.

OBJECTIVES: Since January 23rd 2020, stringent measures for controlling the novel coronavirus epidemics have been gradually enforced and strengthened in mainland China. The detection and diagnosis have been improved as well. However, the daily reported cases staying in a high level make the epidemics trend prediction difficult. METHODS: Since the traditional SEIR model does not evaluate the effectiveness of control strategies, a novel model in line with the current epidemics process and control measures was proposed, utilizing multisource datasets including cumulative number of reported, death, quarantined and suspected cases. RESULTS: Results show that the trend of the epidemics mainly depends on quarantined and suspected cases. The predicted cumulative numbers of quarantined and suspected cases nearly reached static states and their inflection points have already been achieved, with the epidemics peak coming soon. The estimated effective reproduction numbers using model-free and model-based methods are decreasing, as well as new infections, while new reported cases are increasing. Most infected cases have been quarantined or put in suspected class, which has been ignored in existing models. CONCLUSIONS: The uncertainty analyses reveal that the epidemics is still uncertain and it is important to continue enhancing the quarantine and isolation strategy and improving the detection rate in mainland China.

Models for determining the optimal switching time in chemical control of pest with pesticide resistance.

In this paper, we developed a novel resistant equation of pest to pesticide with external~induced resistance and genetic resistance, and then the analytical formula of this equation under different level of dominance of resistance allele is given. Further, we proposed the new methods of modelling pest populations with discrete generations and impulsive chemical control and developed a multi-scale system combining descriptions of pest populations and their genetic evolution. The threshold condition~of pest eradication solution was investigated in more detail, which allows us to address the optimal time when different types of pesticides should be switched. Moreover, we also provided a pesticide switching method guided by the economic injury level (EIL), and then some biological implications have been discussed in terms of pest control.

A general model of hormesis in biological systems and its application to pest management.

Hormesis, a phenomenon whereby exposure to high levels of stressors is inhibitory but low (mild, sublethal and subtoxic) doses are stimulatory, challenges decision-making in the management of cancer, neurodegenerative diseases, nutrition and ecotoxicology. In the latter, increasing amounts of a pesticide may lead to upsurges rather than declines of pests, ecological paradoxes that are difficult to predict. Using a novel re-formulation of the Ricker population equation, we show how interactions between intervention strengths and dose timings, dose-response functions and intrinsic factors can model such paradoxes and hormesis. A model with three critical parameters revealed hormetic biphasic dose and dose timing responses, either in a J-shape or an inverted U-shape, yielding a homeostatic change or a catastrophic shift and hormetic effects in many parameter regions. Such effects were enhanced by repeated pulses of low-level stimulations within one generation at different dose timings, thereby reducing threshold levels, maximum responses and inhibition. The model provides insights into the complex dynamics of such systems and a methodology for improved experimental design and analysis, with wide-reaching implications for understanding hormetic effects in ecology and in medical and veterinary treatment decision-making. We hypothesized that the dynamics of a discrete generation pest control system can be determined by various three-parameter spaces, some of which reveal the conditions for occurrence of hormesis, and confirmed this by fitting our model to both hormetic data from the literature and to a non-hormetic dataset on pesticidal control of mirid bugs in cotton.

A discrete host-parasitoid model with development of pesticide resistance and IPM strategies.

The development of pesticide resistance significantly affects the outcomes of pest control. A quantitative depiction of the effects of pesticide resistance development on integrated pest management (IPM) strategies and pest control outcomes is challenging. To address this problem, a discrete host-parasitoid model with pesticide resistance development and IPM strategies is proposed and analyzed. The threshold condition of pest eradication which reveals the relationship between the development of pest resistance and the rate of natural enemy releases is provided and analyzed, and the optimal rate for releasing natural enemies was obtained based on this threshold condition. Furthermore, in order to reduce adverse effects of the pesticide on natural enemies, the model has been extended to consider the spraying of pesticide and releases of natural enemies at different times. The effects of the dynamic complexity and different resistance development equations on the main results are also discussed.

Multiscale modelling the effects of CI genetic evolution in mosquito population on the control of dengue fever.

Endosymbiotic Wolbachia bacteria are widely applied for the control of dengue fever by manipulating the reproductive mechanism of mosquitoes, including maternal inheritance and cytoplasmic incompatibility (CI). CI means that the offsprings from the matings between Wolbachia infected males and uninfected females can not be hatched. At present, CI effect is assumed as a constant in most of dynamic systems for the spread of Wolbachia. However, their spread may arouse the evolution of mosquitoes to resist CI. Thus, a multiscale model combining a birth-pulse model with a gene-induced discrete model for the frequencies of alleles is proposed to describe the spread of Wolbachia in mosquito population with resistance allele of CI. The main results indicate that the strategy of population eradication can not be realized, while the strategy of population replacement may be realized with the success of sensitive or resistance allele. If appropriate Wolbachia strains can not be selected, then there is a high probability of the failure of population replacement. Moreover, Wolbachia-induced parameters may arouse the catastrophic shifts among stable states of the model. In addition, the demographic parameters and Wolbachia-induced parameters may affect the level and the speed of population replacement and the density of uninfected mosquitoes.

Adaptive release of natural enemies in a pest-natural enemy system with pesticide resistance.

Integrated pest management options such as combining chemical and biological control are optimal for combating pesticide resistance, but pose questions if a pest is to be controlled to extinction. These questions include (i) what is the relationship between the evolution of pesticide resistance and the number of natural enemies released? (ii) How does the cumulative number of natural enemies dying affect the number of natural enemies to be released? To address these questions, we developed two novel pest-natural enemy interaction models incorporating the evolution of pesticide resistance. We investigated the number of natural enemies to be released when threshold conditions for the extinction of the pest population in two different control tactics are reached. Our results show that the number of natural enemies to be released to ensure pest eradication in the presence of increasing pesticide resistance can be determined analytically and depends on the cumulative number of dead natural enemies before the next scheduled release time.

Analytical methods for detecting pesticide switches with evolution of pesticide resistance.

After a pest develops resistance to a pesticide, switching between different unrelated pesticides is a common management option, but this raises the following questions: (1) What is the optimal frequency of pesticide use? (2) How do the frequencies of pesticide applications affect the evolution of pesticide resistance? (3) How can the time when the pest population reaches the economic injury level (EIL) be estimated and (4) how can the most efficient frequency of pesticide applications be determined? To address these questions, we have developed a novel pest population growth model incorporating the evolution of pesticide resistance and pulse spraying of pesticides. Moreover, three pesticide switching methods, threshold condition-guided, density-guided and EIL-guided, are modelled, to determine the best choice under different conditions with the overall aim of eradicating the pest or maintaining its population density below the EIL. Furthermore, the pest control outcomes based on those three pesticide switching methods are discussed. Our results suggest that either the density-guided or EIL-guided method is the optimal pesticide switching strategy, depending on the frequency (or period) of pesticide applications.

Threshold conditions for integrated pest management models with pesticides that have residual effects.

Impulsive differential equations (hybrid dynamical systems) can provide a natural description of pulse-like actions such as when a pesticide kills a pest instantly. However, pesticides may have long-term residual effects, with some remaining active against pests for several weeks, months or years. Therefore, a more realistic method for modelling chemical control in such cases is to use continuous or piecewise-continuous periodic functions which affect growth rates. How to evaluate the effects of the duration of the pesticide residual effectiveness on successful pest control is key to the implementation of integrated pest management (IPM) in practice. To address these questions in detail, we have modelled IPM including residual effects of pesticides in terms of fixed pulse-type actions. The stability threshold conditions for pest eradication are given. Moreover, effects of the killing efficiency rate and the decay rate of the pesticide on the pest and on its natural enemies, the duration of residual effectiveness, the number of pesticide applications and the number of natural enemy releases on the threshold conditions are investigated with regard to the extent of depression or resurgence resulting from pulses of pesticide applications and predator releases. Latin Hypercube Sampling/Partial Rank Correlation uncertainty and sensitivity analysis techniques are employed to investigate the key control parameters which are most significantly related to threshold values. The findings combined with Volterra's principle confirm that when the pesticide has a strong effect on the natural enemies, repeated use of the same pesticide can result in target pest resurgence. The results also indicate that there exists an optimal number of pesticide applications which can suppress the pest most effectively, and this may help in the design of an optimal control strategy.