Oxidation affects pH buffering capacity of myofibrillar proteins via modification of histidine residue and structure of myofibrillar proteins.

The pH buffering capacity is an important functionality of muscle proteins, and muscle foods are susceptible to being oxidized during storage and processing. In order to study the effect of oxidation on the pH buffering capacity of myofibrillar proteins, myofibrils extracted from snakehead fish (Channa argus) were oxidized with H2O2. Results showed that increased oxidation led to loss of free sulfhydryl groups, formation of carbonyl groups, increased surface hydrophobicity, and aggregation of myofibrillar proteins. In addition, there was a significant reduction in the content of histidine in oxidized myofibrillar proteins. The pH buffering capacity of myofibrillar proteins significantly decreased from 3.14 ± 0.03 mM H+/(mL × ΔpH) down to 2.55 ± 0.03 mM H+/(mL × ΔpH) after oxidation with 50 mM H2O2. Both oxidized myofibrillar proteins and histidine showed a high pH buffering capacity at pH near 5.8, which is the histidine pKa value. Here, we hypothesize that oxidation-induced changes in the pH buffering capacity of myofibrillar proteins were driven by oxidative modification of histidine and structural changes of myofibrillar proteins. The significance of this study to food industry may be the awareness that protein oxidation may affect pH through changes in buffering capacity. And the use of antioxidants, especially those targeting at histidine will be promising in addressing this issue.

peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron.

Plant-derived exosome-like nanoparticles (ELNs) have drawn considerable attention for oral treatment of colonic diseases. However, the roles of ELNs derived from garlic on colitis remain unclear. Here, we demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) and trafficking large amounts of functional proteins and microRNAs, stably roam in the gut and confer protection against ulcerative colitis (UC). In mice with DSS-induced colitis, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in which Bacteroides was the dominant respondent genus upon GELNs treatment. Notably, GELNs-enriched peu-MIR2916-p3 specifically promoted the growth of Bacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effects on colitis. Our findings provide new insights into the medicinal application of GELNs and highlight their potential as natural nanotherapeutic agents for preventing and treating UC.

Differential flatness-based adaptive robust tracking control for wheeled mobile robots with slippage disturbances.

Wheeled mobile robots (WMRs) have a wide range of applications in logistics transportation and industrial productions, among which the motion control has always been one of the hot spots in the current WMR researches. However, most of previous designed controllers assumed that the WMR motion had no slippage. Ignoring the slippage factors usually results in a decrease in control performance and even leads to unstable motion. To address such a challenge, a kinematic model with differential flatness is established through dynamic feedback-linearization, which comprehensively considers the multidirectional slippage of mobile robot, including longitudinal and steering slippage. Subsequently, benefited from the one-to-one mapping of states and inputs to flat outputs in differential flat system, an adaptive robust control (ARC) method is proposed to stabilize the system. Different from previous robust control studies, even if the knowledge of the upper bound of system uncertainties is unknown in advance, the proposed adaptive robust controller can still achieve satisfying performance by adaptive estimation of the upper bound of system uncertainties. The effectiveness and feasibility of the proposed method are confirmed by comparative experiments on WMR with slippage disturbance.

Silica Nanoparticle Size Determines the Mechanisms Underlying the Inhibition of Iron Oxide Nanoparticle Uptake by Daphnia magna.

Aquatic environments are complicated systems that contain different types of nanoparticles (NPs). Nevertheless, recent studies of NP toxicity, and especially those that have focused on bioaccumulation have mostly investigated only a single type of NPs. Assessments of the environmental risks of NPs that do not consider co-exposure regimes may lead to inaccurate conclusions and ineffective environmental regulation. Thus, the present study examined the effects of differently sized silica NPs (SiO2 NPs) on the uptake of iron oxide NPs (Fe2O3 NPs) by the zooplankton Daphnia magna. Both SiO2 NPs and Fe2O3 NPs were well dispersed in the experimental medium without significant heteroaggregation. Although all three sizes of SiO2 NPs inhibited the uptake of Fe2O3 NPs, the underlying mechanisms differed. SiO2 NPs smaller than the average mesh size (∼200 nm) of the filtering apparatus of D. magna reduced the accumulation of Fe2O3 NPs through uptake competition, whereas larger SiO2 NPs inhibited the uptake of Fe2O3 NPs mainly by reducing the water filtration rate of the daphnids. Overall, in evaluations of the risks of NPs in the natural environment, the different mechanisms underlying the effects of NPs of different sizes on the uptake of dissimilar NPs should be considered.

Water Extract of Portulaca Oleracea Inhibits PEDV Infection-Induced Pyrolysis by Caspase-1/GSDMD.

Porcine epidemic diarrhea virus (PEDV) belongs to the coronavirus family and the coronavirus genus, causing contact enteric infection in pigs. It is one of the most serious diseases that threatens the pig industry. However, there is currently no specific drug to prevent and treat the disease, indicating that we need to be vigilant about the spread of the disease and the development of anti-PEDV drugs. The dried aerial parts of the plant Portulaca oleracea in the family Portulacaceous, whose decoction can be used to treat acute enteritis, dysentery, diarrhea, and other diseases. This study explored the potential mechanism of water extract of Portulaca oleracea (WEPO) in PEDV-induced pyroptosis in Vero cells. PEDV decreased the viability of Vero cells in a dose- and time-dependent manner, causing cell damage, upregulating the level of intracellular Nlrp3, and inhibiting the level of Gasdermin D (GSDMD) and the activation of Caspase-1. WEPO can inhibit PEDV-induced pyroptosis, reduce the elevation of inflammatory factors caused by infection, and exhibit a dose-dependent effect. Knockdown of Caspase-1 and GSDMD separately can induce the production of the inflammatory factor IL-1ß to significantly decrease and increase, respectively. These results suggest that WEPO can inhibit cell pyroptosis caused by PEDV and that the Caspase-1 and GSDMD pathways play an important role in this process.

Application of the cell-based RT-qPCR assay (C-QPA) for potency detection of the novel trivalent rotavirus vaccine in China.

BACKGROUND: Because of the deficiencies of traditional methods in multivalent rotavirus vaccine potency detection, a cell-based quantitative RT-qPCR assay (C-QPA) was established and validated for specificity, precision, and accuracy. METHODS: In order to further validate the robustness of this method in actual titer detection, the linear range and the practical application under different conditions were tested using monovalent and trivalent rotavirus samples and standards. RESULTS: Results showed that the linear range was 2.0-6.5, 3.9-8.3, and 3.5-8.1 UI (unit of infectivity) for G2, G3, and G4, respectively. Besides, unknown sample with high titer exceeding the linear range can be calculated by dilution. The UIs of serotypes G2, G3, and G4 in monovalent and trivalent rotavirus samples showed a relative deviation ≤4.10%, and the monovalent samples of the same serotype with or without protective agents showed a relative deviation ≤4.28%; the coefficient of variation (CV) of at least 176 tests (548 individual runs) of 3 in vitro-transcribed RNA standards with certain concentrations was not higher than 6.50%; the results of the trivalent samples tested by more than 149 times in 5 years (467 individual runs) showed the CVs lower than 12.66%; 15 samples detected by one laboratory showed a CV lower than 9.83%, while other three samples tested by two independent laboratories showed a CV lower than 6.90%. CONCLUSION: In summary, the C-QPA has good linearity, durability, repeatability, and reproducibility in practical application and has been proved by the authority to be widely used in the production, quality control and release of the recently licensed trivalent vaccine in China.

Protein oxidation-mediated changes in digestion profile and nutritional properties of myofibrillar proteins from bighead carp (Hypophthalmichthys nobilis).

Digestibility is an important factor in accessing the nutritional quality and potential health benefits of protein. In this study, exudates were utilized to incubate myofibrillar proteins (MPs) for simulating the oxidation of MPs in frozen-thawed fish fillets. An in vitro gastrointestinal system was used to investigate the effect of protein oxidation on the digestion profile and nutritional properties of MPs. Results showed that exudates treatment caused the moderate oxidation of MPs and its digestibility thus increased, hydroxyl radical generation system treatment reduced the digestibility significantly. The analysis of SDS-PAGE, tricine-SDS-PAGE, amino acid composition, and peptidomics of digestion products indicates that protein oxidation decreases digestibility by causing protein cross-linking, degradation, and amino acid residues conversion. Additionally, protein oxidation reduces nutritional value of MPs via several ways including loss of essential amino acids, the proportion increase of macromolecular peptides (>2 kDa) in digests, and the percentage decrease of potential bioactive peptides in digests. The present study provides an intuitive insight into the impact of protein oxidation in frozen/thawed fillets on the digestibility of MPs, emphasizing the importance of mitigating protein oxidation to preserve their nutritional quality.

OncoCTMiner: streamlining precision oncology trial matching via molecular profile analysis.

By establishing omics sequencing of patient tumors as a crucial element in cancer treatment, the extensive implementation of precision oncology necessitates effective and prompt execution of clinical studies for approving molecular-targeted therapies. However, the substantial volume of patient sequencing data, combined with strict clinical trial criteria, increasingly complicates the process of matching patients to precision oncology studies. To streamline enrollment in these studies, we developed OncoCTMiner, an automated pre-screening platform for molecular cancer clinical trials. Through manual tagging of eligibility criteria for 2227 oncology trials, we identified key bio-concepts such as cancer types, genes, alterations, drugs, biomarkers and therapies. Utilizing this manually annotated corpus along with open-source biomedical natural language processing tools, we trained multiple named entity recognition models specifically designed for precision oncology trials. These models analyzed 460 952 clinical trials, revealing 8.15 million precision medicine concepts, 9.32 million entity-criteria-trial triplets and a comprehensive precision oncology eligibility criteria database. Most significantly, we developed a patient-trial matching system based on cancer patients' clinical and genetic profiles, which can seamlessly integrate with the omics data analysis platform. This system expedites the pre-screening process for potentially suitable precision oncology trials, offering patients swifter access to promising treatment options. Database URL  https://oncoctminer.chosenmedinfo.com.

Dual cryoprotective and antioxidant effects of young apple polyphenols on myofibrillar protein degradation and gelation properties of bighead carp mince during frozen storage.

Commercial cryoprotectants can delay quality loss in frozen fish mince, but they are associated with a sweet taste and high calorie content. Young apple polyphenols (YAP), extracted from unripe apples, show potential as an alternative cryoprotectant. This study evaluated the cryoprotective effect of YAP at varying levels (0.3%, 0.7%, and 1%) in unwashed bighead carp mince. The changes in sulfhydryl content, carbonyl content, thiobarbituric acid reactive substances, intrinsic fluorescence intensity, and Fourier transform infrared spectrum indicated that YAP retarded oxidation and structural changes in myofibrillar proteins during the first 8 weeks of frozen storage, as well as lipid oxidation, which protected the structure of myofibrillar protein. At higher concentrations (0.7% and 1%), YAP maintained gel properties, gel springiness, and water-holding capacity of the gel prepared from frozen fish mince, potentially through the promotion of cross-linking of myofibrillar proteins. Overall, YAP can be used as a cryoprotectant and antioxidant in fish mince. PRACTICAL APPLICATION: Our research found that young apple polyphenols have the potential to be an alternative to commercial cryoprotectants. Young apple polyphenols may be used as a sugar-free and healthy cryoprotectant for frozen fish mince production in the future.

Eurotium cristatum from Fu Brick Tea Promotes Adipose Thermogenesis by Boosting Colonic Akkermansia muciniphila in High-Fat-Fed Obese Mice.

This study investigated the potential fat-thermogenic effects of Eurotium cristatum, and elucidated the underlying mechanisms. The 12-week administration of E. cristatum in HFD-fed obese mice reduced body weight and improved glucolipid metabolism disorders. The administration of E. cristatum also efficiently promoted thermogenesis by increasing the expression of UCP1 and PRDM16 in both interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of HFD-fed mice. Furthermore, E. cristatum shaped the gut microbiome by increasing the abundance of Parabacteroides and Akkermansia muciniphila, and also elevated the levels of cecal short-chain fatty acids, particularly propionate and acetate. Of note, A. muciniphila was highly negatively correlated with body weight gain (r = -0.801, p < 0.05) and the iWAT index (r = -0.977, p < 0.01), suggesting that A. muciniphila may play an important role in the thermogenic mobilization induced by E. cristatum. Continuous supplementation with A. muciniphila suppressed adipose accumulation, improved glucolipid metabolism, and enhanced the thermogenic activity of iWAT and iBAT. Collectively, our results propose that boosted A. muciniphila acts as a key microbe in tea-derived probiotic E. cristatum-mediated fat-thermogenic and anti-obesity effects.

Ultrahigh areal capacity and long cycling stability of sodium metal anodes boosted using a 3D-printed sodiophilic MXene/rGO microlattice aerogel.

Sodium metal has emerged as a highly promising anode material for sodium-based batteries, owing to its intrinsic advantages, including its high theoretical capacity, low working plateau and low cost. However, the uncontrolled formation of sodium dendrites accompanied by unrestricted volume expansion severely limits its application. To tackle these issues, we propose an approach to address these issues by adopting a three-dimensional (3D) structure of Ti3C2Tx/reduced graphene oxide (Ti3C2Tx/rGO) constructed by a direct-ink writing (DIW) 3D printing technique as the Na metal anode host electrode. The combination of the 3D-printed rGO skeleton offering artificial porous structures and the incorporation of sodiophilic Ti3C2Tx nanosheets provides abundant nucleation sites and promotes uniform sodium metal deposition. This specially designed architecture significantly enhances the Na metal cycling stability by effectively inhibiting dendrite formation. The experimental results show that the designed Ti3C2Tx/rGO electrode can achieve a high coulombic efficiency (CE) of 99.91% after 1800 cycles (3600 h) at 2 mA cm-2 with 2 mA h cm-2. Notably, the adopted electrodes exhibit a long life span of more than 1400 h with a high CE over 99.93% when measured with an ultra-high capacity of 50 mA h cm-2 at 5 mA cm-2. Furthermore, a 3D-printed full cell consisting of a Na@Ti3C2Tx/rGO anode and a 3D-printed Na3V2(PO4)3C-rGO (NVP@C-rGO) cathode was successfully demonstrated. This 3D-printed cell could provide a notable capacity of 85.3 mA h g-1 at 100 mA g-1 after 500 cycles. The exceptional electrochemical performance achieved by the 3D-printed full cell paves the way for the development of practical sodium metal anodes.

Immunogenicity and safety of a new hexavalent rotavirus vaccine in Chinese infants: A randomized, double-blind, placebo-controlled phase 2 clinical trial.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.

Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial.

Background: Updated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac. Methods: A randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged ≥18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain. Results: Between June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers' (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI ≥1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio ≥2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified. Conclusion: The Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350.

[Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle].

OBJECTIVE: To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle. METHODS: A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence. RESULTS: After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling. CONCLUSION: Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Accumulation of nanoplastics in human cells as visualized and quantified by hyperspectral imaging with enhanced dark-field microscopy.

Nanoplastic (NP) pollution is receiving increasing attention regarding its potential effects on human health. The identification and quantification of intracellular NPs are prerequisites for an accurate risk assessment, but appropriate methods are lacking. Here we present a label-free technique to simultaneously visualize and quantify the bioaccumulation of NPs based on hyperspectral imaging with enhanced dark-field microscopy (HSI-DFM). Using polystyrene NPs (PS NPs) as representative particles, the construction of a hyperspectral library was optimized first with more accurate NP identification achieved when the library was based on intracellular instead of extracellular PS NPs. The PS NPs used herein were labeled with a green fluorescent dye so that the accuracy of HSI-DFM in identifying and quantifying intracellular NPs can be evaluated, by comparing the results with those obtained by fluorescence microscopy and flow cytometry. The validation of HSI-DFM for use in determinations of the NP concentration at the single-cell level allows analyses of the accumulation kinetics of NPs in single living cells. The utility of HSI-DFM in different cell lines and with NPs differing in their chemical composition was also demonstrated. HSI-DFM therefore provides a new approach to studies of the accumulation and distribution of NPs in human cells.

Preoperative computed tomography-guided transscapular sens-cure needle localization for pulmonary nodule located behind the scapula.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is an approach that is commonly used to resect pulmonary nodules (PNs). However, when these PNs are located behind the scapula, a transscapular access approach is generally required. In this study, the safety, efficacy, and feasibility of preoperative computed tomography (CT)-guided Sens-cure needle (SCN) localization was assessed for PNs located behind the scapula. METHODS: From January 2020 - June 2022, a total of 122 PN patients in our hospital underwent preoperative CT-guided SCN localization and subsequent VATS resection, of whom 12 (9.8%) exhibited PNs behind the scapula necessitating a transscapular approach for this localization procedure. RESULTS: This study included 12 patients, each of whom had one PN located behind the scapula. The CT-guided transscapular SCN localization approach was successful in all patients, and no complications near the operative site were observed. The median localization time was 12 min, and 2 (16.7%) and 1 (8.3%) patients respectively developed pneumothorax and pulmonary hemorrhage after the localization procedure was complete. Wedge resection procedures for these PNs achieved technical success in all cases. Four patients were diagnosed with invasive adenocarcinomas and subsequently accepted lobectomy and systematic lymph node dissection. The median VATS duration and the median blood loss was 80 min and 10 mL, respectively. In total, 3, 5, and 4 PNs were respectively diagnosed as benign, mini-invasive adenocarcinomas, and invasive adenocarcinomas. CONCLUSION: Preoperative CT-guided transscapular SCN localization represents a safe, straightforward, and effective means of localizing PNs present behind the scapula.

Focus prediction of medical microscopic images based on Lightweight Densely Connected with Squeeze-and-Excitation Network.

Due to the demand for sample observation, optical microscopy has become an essential tool in the fields of biology and medicine. In addition, it is impossible to maintain the living sample in focus over long-time observation. Rapid focus prediction which involves moving a microscope stage along a vertical axis to find an optimal focus position, is a critical step for high-quality microscopic imaging of specimens. Current focus prediction algorithms, which are time-consuming, cannot support high frame rate imaging of dynamic living samples, and may introduce phototoxicity and photobleaching on the samples. In this paper, we propose Lightweight Densely Connected with Squeeze-and-Excitation Network (LDSE-NET). The results of the focusing algorithm are demonstrated on a public dataset and a self-built dataset. A complete evaluation system was constructed to compare and analyze the effectiveness of LDSE-NET, BotNet, and ResNet50 models in multi-region and multi-multiplier prediction. Experimental results show that LDSE-NET is reduced to 1E-05 of the root mean square error. The accuracy of the predicted focal length of the image is increased by 1 ~ 2 times. Training time is reduced by 33.3%. Moreover, the volume of the model only reaches the KB level, which has the characteristics of being lightweight.

Physiologically Based Pharmacokinetic Modeling to Simulate CYP3A4-Mediated Drug-Drug Interactions for Pyrotinib.

INTRODUCTION: Pyrotinib is a newly developed tyrosine kinase inhibitor whose in vivo clearance relies heavily on cytochrome P450 3A4 (CYP3A4) activity. Clinical trials are ongoing to explore the effects of coadministration with CYP3A4 perpetrators on pyrotinib exposure. The present study aims to utilize physiologically based pharmacokinetic (PBPK) modeling to predict CYP3A4-based drug interactions of pyrotinib. METHODS: Pyrotinib PBPK model was developed in the PK-Sim® multicompartmental physiology structure. Physiochemical parameters were obtained from the literature, and clearance-related parameters were optimized by fitting clinical single-dose pharmacokinetic data. Pharmacokinetic parameters from the model output were compared with the observed data to validate the model predictive performance. Using validated CYP3A4 perpetrator models, we conducted PBPK simulations for drug interactions in a virtual population to explore the impacts of comedication with these perpetrators. RESULTS: The PBPK model accurately describes pyrotinib single- and multi-dose pharmacokinetics. The model also predicts dramatic exposure change of pyrotinib in the presence of itraconazole and rifampicin, though the impact of rifampicin is somewhat underestimated. According to model predictions, coadministration with typical potent or moderate CYP3A4 perpetrators increases pyrotinib concentration by over sixfold, extinguishing the possibility of dose adjustment for pyrotinib. A weak CYP3A4 inhibitor has minimal influence on pyrotinib pharmacokinetics. CONCLUSION: PBPK modeling provides valuable information to avoid irrational medication when receiving pyrotinib chemotherapy.

The potential of curcumin-based co-delivery systems for applications in the food industry: Food preservation, freshness monitoring, and functional food.

Currently, curcumin-based co-delivery systems are receiving widespread attention. However, a systematic summary of the possibility of curcumin-based co-delivery systems used for the food industry from multiple directions based on the functional characteristics of curcumin is lacking. This review details the different forms of curcumin-based co-delivery systems including the single system of nanoparticle, liposome, double emulsion, and multiple systems composed of different hydrocolloids. The structural composition, stability, encapsulation efficiency, and protective effects of these forms are discussed comprehensively. The functional characteristics of curcumin-based co-delivery systems are summarized, involving biological activity (antimicrobial and antioxidant), pH-responsive discoloration, and bioaccessibility/bioavailability. Correspondingly, potential applications for food preservation, freshness detection, and functional foods are introduced. In the future, more novel co-delivery systems for active ingredients and food matrices should be developed. Besides, the synergistic mechanisms between active ingredients, delivery carrier/active ingredient, and external physical condition/active ingredient should be explored. In conclusion, curcumin-based co-delivery systems have the potential to be widely used in the food industry.