Transformed pupil-function misalignment calibration strategy for Fourier ptychographic microscopy.

Fourier ptychographic microscopy (FPM) is an enabling quantitative phase imaging technique with both high-resolution (HR) and wide field-of-view (FOV), which can surpass the diffraction limit of the objective lens by employing an LED array to provide angular-varying illumination. The precise illumination angles are critical to ensure exact reconstruction, while it's difficult to separate actual positional parameters in conventional algorithmic self-calibration approaches due to the mixing of multiple systematic error sources. In this paper, we report a pupil-function-based strategy for independently calibrating the position of LED array. We first deduce the relationship between positional deviation and pupil function in the Fourier domain through a common iterative route. Then, we propose a judgment criterion to determine the misalignment situations, which is based on the arrangement of LED array in the spatial domain. By combining the mapping of complex domains, we can accurately solve the spatial positional parameters concerning the LED array through a boundary-finding scheme. Relevant simulations and experiments demonstrate the proposed method is accessible to precisely correct the positional misalignment of LED array. The approach based on the pupil function is expected to provide valuable insights for precise position correction in the field of microscopy.

A Unique Combination of Mn2+ and Aluminum Adjuvant Acted the Synergistic Effect.

Introduction: The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong immunocompetence and will become an enormous potential adjuvant. Here, we described a novel combination of Mn2+ plus aluminum hydroxide (AH) adjuvant that significantly exhibited the synergistic immune effect. Methodology. Initially, IsdB3 proteins as the immune-dominant fragment of IsdB proteins derived from Staphylococcus aureus (S. aureus) were prepared. IsdB3 proteins were identified by western blotting. Furthermore, we immunized C57/B6 mice with IsdB3 proteins plus Mn2+ and AH adjuvant. After the second immunization, the proliferation of lymphocytes was measured by the cell counting kit-8 (CCK-8) and the level of IFN-γ, IL-4, IL-10, and IL-17 cytokine from spleen lymphocytes in mice and generation of the antibodies against IsdB3 in serum was detected with ELISA, and the protective immune response was assessed through S. aureus challenge. Results: IsdB3 proteins plus Mn2+ and AH obviously stimulated the proliferation of spleen lymphocytes and increased the secretion of IFN-γ, IL-4, IL-10, and IL-17 cytokine in mice, markedly enhanced the generation of the antibodies against IsdB3 in serum, observably decreased bacterial load in organs, and greatly improved the survival rate of mice. Conclusion: These data showed that the combination of Mn2+ and AH significantly acted a synergistic effect, reinforced the immunogenicity of IsdB3, and offered a new strategy to increase vaccine efficiency.

Prediction of Hydration Heat for Diverse Cementitious Composites through a Machine Learning-Based Approach.

Hydration plays a crucial role in cement composites, but the traditional methods for measuring hydration heat face several limitations. In this study, we propose a machine learning-based approach to predict hydration heat at specific time points for three types of cement composites: ordinary Portland cement pastes, fly ash cement pastes, and fly ash-metakaolin cement composites. By adjusting the model architecture and analyzing the datasets, we demonstrate that the optimized artificial neural network model not only performs well during the learning process but also accurately predicts hydration heat for various cement composites from an extra dataset. This approach offers a more efficient way to measure hydration heat for cement composites, reducing the need for labor- and time-intensive sample preparation and testing. Furthermore, it opens up possibilities for applying similar machine learning approaches to predict other properties of cement composites, contributing to efficient cement research and production.

Factors affecting vancomycin-resistant Enterococcus faecium colonization of in-hospital patients in different wards.

Objectives: The prevalence of vancomycin-resistant Enterococcus faecium (VRE) infection at a medical center in Eastern Taiwan rose to 80.6%, exceeding the average prevalence of 55.6% among all medical centers nationwide during the same period. In recent years, the number of cases of VRE infection detected among hospitalized patients has increased annually. However, most of these patients in different wards are asymptomatic carriers. Therefore, restricting active screening to high-risk units will not improve the current situation, and it is necessary to review the risk factors for VRE colonization to provide a reference for future infection control policies. Materials and Methods: Between 2014 and 2019, there were 3188 VRE-positive cultures reported at our institution, as per the electronic medical records system. Results: In the medical and surgical wards, patients who received penicillin (odds ratios [ORs]: 2.84 and 4.16, respectively) and third-generation cephalosporins (ORs: 3.17 and 6.19, respectively) were at higher risk of VRE colonization. In intensive care units, the use of carbapenems (OR: 2.08) was the most significant variable. Conclusion: This study demonstrated that the risk factors for VRE colonization differed between wards. Thus, policies should be established according to the attributes of patients in each ward, and active screening tests should be performed according to individual risks, instead of a policy for comprehensive mass screening.

Disease Burden of Colorectal Cancer in China from 1990 to 2019: Age- and Sex-Specific Time Trends and 10-Year Forecast.

INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent malignant tumor worldwide and the second leading cause of cancer-related death. This study aimed at reporting the disease burden of CRC in China from 1990 to 2019 and predicting the trend of mortality burden over the next 10 years. METHODS: The age-period-cohort model was implemented to analyze the trends of mortality from CRC in China from 1990 to 2019, and the autoregressive integrated moving average (ARIMA) model was used to predict the trends of CRC incidence and mortality from 2020 to 2029. RESULTS: From 1990 to 2019, the incidence of CRC in China increased from 105,911 cases (95% uncertainty interval [UI]: 93,808-119,021) to 607,900 cases (95% UI: 521,805-708,420). The age-standardized incidence rate increased from 12.52 per 100,000 (95% UI: 11.15-14.03) to 30.55 per 100,000 (95% UI: 26.37-35.5), with an estimated annual percentage change (EAPC) of 3.66 (95% confidence interval [CI]: 3.37-3.95), showing an upward trend. The age-standardized mortality rate increased from 10.18 per 100,000 (95% UI: 9.03-11.37) to 13.86 per 100,000 (95% UI: 11.92-16.01), with an EAPC of 1.39 (95% CI: 1.14-1.63), also showing an upward trend. The age group with the highest incidence and mortality in 2019 was 65-69 years old for both sexes, and the age group with the highest mortality was 70-74 years old. Males had higher relative risks of incidence and mortality than females. Low-calcium diet was the risk factor for both sexes and females alone in 1990, while low-milk diet was the risk factor in 2019; however, smoking remained the risk factor for males. The ARIMA model predicted an increase in both disease and mortality burden of CRC over the next 10 years. CONCLUSION: The disease and mortality burden of CRC in China showed an overall upward trend from 1990 to 2019, with higher burden in males than females, and the situation remains extremely severe in the next decade.

Bacteriophage endolysin powders for inhaled delivery against pulmonary infections.

Endolysins are bacteriophage-encoded enzymatic proteins that have great potential to treat multidrug-resistant bacterial infections. Bacteriophage endolysins Cpl-1 and ClyJ-3 have shown promising antimicrobial activity against Streptococcus pneumoniae, which causes pneumonia in humans. This is the first study to investigate the feasibility of spray-dried endolysins Cpl-1 and ClyJ-3 with excipients to produce inhalable powders. The two endolysins were individually tested with leucine and sugar (lactose or trehalose) for spray drying method followed by characterization of biological and physico-chemical properties. A complete loss of ClyJ-3 bioactivity was observed after atomization of the liquid feed solution（before the drying process）, while Cpl-1 maintained its bioactivity in the spray-dried powders. Cpl-1 formulations containing leucine with lactose or trehalose showed promising physico-chemical properties (particle size, crystallinity, hygroscopicity, etc.) and aerosol performances (fine particle fraction values above 65%). The results indicated that endolysin Cpl-1 can be formulated as spray dried powders suitable for inhaled delivery to the lungs for the potential treatment of pulmonary infections.

A Study on the Willingness and Factors Influencing the Digital Upgrade of Rural E-Commerce.

The current problems of the low digital upgrading of rural e-commerce, single marketing method and high homogeneous competition will seriously hinder the development of rural e-commerce and rural revitalization. Therefore, finding how to guide the digital upgrading of rural e-commerce will be a key step in achieving rural revitalization and common prosperity. Based on 1387 Zhejiang rural e-commerce digital upgrading questionnaires, this paper analyzes willingness regarding rural e-commerce digital upgrading and its influencing factors using planned behavior theory and structural equation modeling. The findings show that (1) behavioral attitudes are the main influencing factors of upgrading willingness, and subjective norms are secondary influencing factors; (2) in terms of the behavioral attitudes of rural e-merchants, the greater the proportion of their online sales or the higher the proportion of online income, the better behavioral attitudes formed on this basis can promote the willingness to digitally upgrade rural e-merchants; (3) in terms of subjective norms, when rural e-merchant subjects perceive that the increased local participation in e-merchant association is too large or online income tends to saturate the total income, the more subjective norms can influence their willingness to digitally upgrade.

Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment.

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.

The effects of different doses of inhaled bacteriophage therapy for Pseudomonas aeruginosa pulmonary infections in mice.

OBJECTIVES: Inhaled phage therapy has been revisited as a potential treatment option for respiratory infections caused by multidrug-resistant Pseudomonas aeruginosa; however, there is a distinct gap in understanding the dose-response effect. The aim of this study was to investigate the dose-response effect of Pseudomonas-targeting phage PEV31 delivered by the pulmonary route in a mouse lung infection model. METHODS: Neutropenic BALB/c mice were infected with multidrug-resistant P. aeruginosa (2 × 104 colony-forming units) through the intratracheal route and then treated with PEV31 at three different doses of 7.5 × 104 (Group A), 5 × 106 (Group B), and 5 × 108 (Group C) plaque-forming units, or phosphate-buffered saline at 2 hours postinoculation. Mice (n = 5-7) were euthanized at 2 hours and 24 hours postinfection, and lungs, kidneys, spleen, liver, bronchoalveolar lavage fluid, and blood were collected for bacteria and phage enumeration. RESULTS: At 24 hours postinfection, all phage-treated groups exhibited a significant reduction in pulmonary bacterial load by 1.3-1.9 log10, independent of the delivered phage dose. The extent of phage replication was negatively correlated with the dose administered, with log10 titre increases of 6.2, 2.7, and 9 for Groups A, B, and C, respectively. Phage-resistant bacterial subpopulations in the lung homogenate samples harvested at 24 hours postinfection increased with the treatment dose (i.e. 30%, 74%, and 91% in respective Groups A-C). However, the mutants showed increased susceptibility to ciprofloxacin, impaired twitching motility, and reduced blue-green pigment production. The expression of the inflammatory cytokines (IL-1ß and IL-6, and TNF-α) was suppressed with increasing PEV31 treatment dose. DISCUSSION: This study provides the dose-response effect of inhaled phage therapy that may guide dose selection for treating P. aeruginosa respiratory infections in humans.

Advances in the development of antimicrobial peptides and proteins for inhaled therapy.

Antimicrobial peptides and proteins (APPs) are becoming increasingly important in targeting multidrug-resistant (MDR) bacteria. APPs is a rapidly emerging area with novel molecules being produced and further optimised to enhance antimicrobial efficacy, while overcoming issues associated with biologics such as potential toxicity and low bioavailability resulting from short half-life. Inhalation delivery of these agents can be an effective treatment of respiratory infections owing to the high local drug concentration in the lungs with lower exposure to systemic circulation hence reducing systemic toxicity. This review describes the recent studies on inhaled APPs, including in vitro and in vivo antimicrobial activities, toxicity assessments, and formulation strategies whenever available. The review also includes studies on combination of APPs with other antimicrobial agents to achieve enhanced synergistic antimicrobial effect. Since different APPs have different biological and chemical stabilities, a targeted formulation strategy should be considered for developing stable and inhalable antimicrobial peptides and proteins. These strategies include the use of sodium chloride to reduce electrostatic interaction between APP and extracellular DNA in sputum, the use of D-enantiomers or dendrimers to minimise protease-mediated degradation and or the use of prodrugs to reduce toxicity. Although great effort has been put towards optimising the biological functions of APPs, studies assessing biological stability in inhalable aerosols are scarce, particularly for novel molecules. As such, formulation and manufacture of inhalable liquid and powder formulations of APPs are underexplored, yet they are crucial areas of research for clinical translation.

A program to improve the quality of dental unit water in a medical center.

ABSTRACT: The water quality of dental unit waterlines (DUWLs) is associated with patient safety. No program for DUWL water quality improvement has been formulated since the time they were established 20 years ago. This study provides an improvement program for the quality of dental unit water. The improvement program was implemented step by step: discharge of DUWLs for 5 minutes in the morning before clinical service to flush out the water left in the pipeline overnight; weekly disinfection of the handpiece connector with 75% alcohol and replacement of the old connector when the water quality of the same dental chair unit (DCU) was continuously found to be unqualified; monthly disinfection of the water supply system and pipeline; and establishment of DCU maintenance work standards and staff education and training. From 2016 to 2018, the water quality of 18 DCUs was tested by microorganism culture. The colonies >200 colony forming unit were categorized as unqualified. This program was divided into a pre-test phase, Phase 1, a maintenance phase, and Phase 2. A Chi-square test was used to calculate the difference of unqualified water quality numbers between each phase of the improvement program. In the pre-test phase, the water quality rate (high quality number/high-quality number + low-quality number) was 58.3%. In Phase 1, the quality rate before and after the intervention was 64.8% (35/54) and 92.2% (83/90) (P < .001), respectively. After Phase 1, the quality rate reached 100%. However, the quality rate dropped to 75% during the maintenance phase. Then, we proceeded into Phase 2 of the improvement program by further monthly disinfection to DUWLs. In Phase 2, the quality rate was 62/73 (84.9%) and improved to 142/144 (98.6%) after the intervention (P < .001). The quality rate reached 100% once again and was maintained at 100% thereafter. In conclusion, the 4 steps of the improvement program improved the water quality of the DUWL, which is important for patient safety.

Symmetric Graphene Dielectric Nanowaveguides as Ultra-Compact Photonic Structures.

A symmetric graphene plasmon waveguide (SGPWG) is proposed here to achieve excellent subwavelength waveguiding performance of mid-infrared waves. The modal properties of the fundamental graphene plasmon mode are investigated by use of the finite element method. Due to the naturally rounded tips, the plasmon mode in SGPWG could achieve a normalized mode field area of ~10-5 (or less) and a figure of merit over 400 by tuning the key geometric structure parameters and the chemical potential of graphene. In addition, results show that the modal performance of SGPWG seems to improve over its circular counterparts. Besides the modal properties, crosstalk analysis indicates that the proposed waveguide exhibits extremely low crosstalk, even at a separation distance of 64 nm. Due to these excellent characteristics, the proposed waveguide has promising applications in ultra-compact integrated photonic components and other intriguing nanoscale devices.

Effects of biodiesels on the physicochemical properties and oxidative reactivity of diesel particulates: A review.

Particulate emissions from the combustion of diesel have always been the main concern, especially in recent years, with continuously stringent particulate emission regulation for diesel engines. To alleviate the problem, biodiesel has been received great attention because of its being environment-friendly, widely available and renewable. The application of biodiesel in diesel engines changes the combustion process, thus varies physicochemical property of the particulate matter (PM) formed, which in turn influences the oxidative reactivity of soot particles. In view of this, it is particularly important to analyze soot particles from the diesel engine fueled with biodiesels. This review focus on the effects of biodiesels on the physicochemical properties of soot particles, such as surface morphology, nanostructure, active surface area, element composition, elemental and organic carbon contents, surface functional groups, sp2 and sp3 hybridizations, etc. The impact of engine operating conditions (i.e. engine load, engine speed, fuel injection timing, fuel injection pressure, exhaust gas recirculation, etc.) on characteristics of soot particles from diesel engines powered by biodiesel is also discussed. Whereafter, the relationships between soot physicochemical characteristics and soot oxidative reactivity are reviewed. Finally, the main conclusions are outlined as well as the proposed research work in the future.

Synergistic activity of phage PEV20-ciprofloxacin combination powder formulation-A proof-of-principle study in a P. aeruginosa lung infection model.

Combination treatment using bacteriophage and antibiotics is potentially an advanced approach to combatting antimicrobial-resistant bacterial infections. We have recently developed an inhalable powder by co-spray drying Pseudomonas phage PEV20 with ciprofloxacin. The purpose of this study was to assess the in vivo effect of the powder using a neutropenic mouse model of acute lung infection. The synergistic activity of PEV20 and ciprofloxacin was investigated by infecting mice with P. aeruginosa, then administering freshly spray-dried single PEV20 (106 PFU/mg), single ciprofloxacin (0.33 mg/mg) or combined PEV20-ciprofloxacin treatment using a dry powder insufflator. Lung tissues were then harvested for colony counting and flow cytometry analysis at 24 h post-treatment. PEV20 and ciprofloxacin combination powder significantly reduced the bacterial load of clinical P. aeruginosa strain in mouse lungs by 5.9 log10 (p < 0.005). No obvious reduction in the bacterial load was observed when the animals were treated only with PEV20 or ciprofloxacin. Assessment of immunological responses in the lungs showed reduced inflammation associating with the bactericidal effect of the PEV20-ciprofloxacin powder. In conclusion, this study has demonstrated the synergistic potential of using the combination PEV20-ciprofloxacin powder for P. aeruginosa respiratory infections.

Pharmacokinetics and Time-Kill Study of Inhaled Antipseudomonal Bacteriophage Therapy in Mice.

Inhaled bacteriophage (phage) therapy is a potential alternative to conventional antibiotic therapy to combat multidrug-resistant (MDR) Pseudomonas aeruginosa infections. However, pharmacokinetics (PK) and pharmacodynamics (PD) of phages are fundamentally different from antibiotics and the lack of understanding potentially limits optimal dosing. The aim of this study was to investigate the in vivo PK and PD profiles of antipseudomonal phage PEV31 delivered by pulmonary route in immune-suppressed mice. BALB/c mice were administered phage PEV31 at doses of 107 and 109 PFU by the intratracheal route. Mice (n = 4) were sacrificed at 0, 1, 2, 4, 8, and 24 h posttreatment and various tissues (lungs, kidney, spleen, and liver), bronchoalveolar lavage fluid, and blood were collected for phage quantification. In a separate study combining phage with bacteria, mice (n = 4) were treated with PEV31 (109 PFU) or phosphate-buffered saline (PBS) at 2 h postinoculation with MDR P. aeruginosa Infective PEV31 and bacteria were enumerated from the lungs. In the phage-only study, the PEV31 titer gradually decreased in the lungs over 24 h, with a half-life of approximately 8 h for both doses. In the presence of bacteria, in contrast, the PEV31 titer increased by almost 2-log10 in the lungs at 16 h. Furthermore, bacterial growth was suppressed in the PEV31-treated group, while the PBS-treated group showed exponential growth. Of the 10 colonies tested, four phage-resistant isolates were observed from the lung homogenates sampled at 24 h after phage treatment. These colonies had a different antibiogram to the parent bacteria. This study provides evidence that pulmonary delivery of phage PEV31 in mice can reduce the MDR bacterial burden.

Can bacteriophage endolysins be nebulised for inhalation delivery against Streptococcus pneumoniae?

Endolysins are bacteriophage-derived protein molecules highly effective for bacterial killing. Cpl-1 and ClyJ-3 are native and chimeric endolysins, respectively, having antimicrobial activity against Streptococcus pneumoniae which causes lung infections. We conducted the first feasibility study on nebulisation of Cpl-1 and ClyJ-3, with a focus on the antimicrobial activity, structural changes of the proteins and aerosol performance. Bacterial colony counts, live cell imaging and Fourier-transform infrared(FTIR) spectroscopy were used to evaluate the proteins before and after jet or vibrating mesh nebulisation. These nebulised aerosols were inhalable with a volume median size of 3.8-4.2 µm (span 1.1-2.3) measured by laser diffraction. How-ever, neb-u-li-sa-tion caused al-most com-plete loss in bioac-tiv-ity of ClyJ-3, which were corroborated with the live cell imaging observation and protein structural damage with a large intensity reduction in the amide absorption bands between 1300 and 1700 cm-1. In contrast, the bactericidal activity of Cpl-1 showed no significant difference (p ≥ 0.05) before and after mesh nebulisation with 4.9 and 4.6-log10 bacterial count reduction, respectively. However, jet nebulisation reduced the bioactivity of Cpl-1 and the effect was time-dependent showing 1.7, 1.0-log10 bacterial count reduction at 7 and 14 min with complete loss of antimicrobial activity at 21 min after nebulisation, respectively. The results were consistent with time-dependent changes in live cell images and FTIR amide band changes at 1655, 1640, 1632 and 1548 cm-1. In conclusion, it is feasible to nebulise endolysins for inhalation delivery but it depends on both the protein and the nebuliser, with the mesh nebuliser being the preferred choice.

Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus.

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), which can cause hemorrhagic fever-like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups--severe or non-severe--based on disease severity. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, interleukin-6, interferon (IFN)-γ, IFN- γ-induced protein (IP)-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.

[Mathematic models of cucumber net photosynthesis rate responding to CO2 concentration, temperature, and illumination intensity].

With two cucumber varieties (greenhouse variety Jinyou No. 1 and open-field variety Jinyan No. 4) as test materials, this paper measured their net photosynthesis rate (P(n)) under given environmental conditions including CO2 concentration, temperature and illumination intensity in phytotron, and the responses of P(n) (y) to these factors were modeled by mathematic methods, which could be described as y = exp (- 242. 1217/x1) [61.0202 - 0.11 (x2 - 30.926)2] exp (-272. 8874/x3) + 0.9355 for Jinyou No. 1, and y = exp (- 179.8803/x1) [50.0771-0.0609 (x2 -34.3455)2] exp (-267.9653/x3) + 0.7377 for Jinyan No. 4, where x1, x2 and x3 represented the values of CO2 concentration, temperature, and illumination intensity, respectively. The response of P(n) to temperature accorded with conic function, while its responses to CO2 concentration and illumination intensity accorded with exponential function.