[Critical quality attribute characterization of big brand TCM: taste formulation optimization strategy and application of Xiaoer Ganmao Oral Liquid based on taste quality attribute].

The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.

NIR robustness model of variable selection investigation of critical quality attributes coupled with different simulate noises by prediction capability and reproducibility.

variable selection is critical to select characteristic variables of critical quality attributes to improve model performance and interpret the identified variables in multivariate calibration. However, classical variable selection methods were developed and optimized by the prediction error. It is rare for the robustness evaluation of variable selection methods. In this study, the robustness of four different variable selection methods was investigated by adding different types of simulate noises to validation set and calibration and validation sets, respectively. The reproducibility as well as root mean squared error of prediction (RMSEP) were used together as common measure in assessing the robustness of different variable selection methods. The robustness of four variable selection methods method was investigated using two near infrared (NIR) datasets including open-source dataset of corn and Chinese herbal medicine (CHM) dataset. The result illustrated that variable importance in projection (VIP) was substantially more robust to additive noise, with smaller RMSEP value and high reproducibility. This provides a novel strategy for the reliability evaluation of variable selection methods in NIR model of critical quality attributes.

Biomembrane-Functionalized Micromotors: Biocompatible Active Devices for Diverse Biomedical Applications.

There has been considerable interest in developing synthetic micromotors with biofunctional, versatile, and adaptive capabilities for biomedical applications. In this perspective, cell membrane-functionalized micromotors emerge as an attractive platform. This new class of micromotors demonstrates enhanced propulsion and compelling performance in complex biological environments, making them suitable for various in vivo applications, including drug delivery, detoxification, immune modulation, and phototherapy. This article reviews various proof-of-concept studies based on different micromotor designs and cell membrane coatings in these areas. The review focuses on the motor structure and performance relationship and highlights how cell membrane functionalization overcomes the obstacles faced by traditional synthetic micromotors while imparting them with unique capabilities. Overall, the cell membrane-functionalized micromotors are expected to advance micromotor research and facilitate its translation towards practical uses.

[Critical quality attribute assessment of big brand traditional Chinese medicine: visualization of blending process for rare medicines in Tongren Niuhuang Qingxin Pills based on spatial distribution uniformity].

The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.

[Criticalquality attribute assessment of big brand traditional Chinese medicine: visualization method for quality control of Ginkgo Leaves Tablets based on spatial distribution uniformity].

Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.

[Critical quality attribute assessment of big brand traditional Chinese medicine: process quality control method of Suhuang Zhike Capsules intermediate based on physical properties of powder and granules].

The physical properties of powder and granules are the critical quality attributes for the process control of Suhuang Zhike Capsules, a big brand traditional Chinese medicine. This paper took the production of 25 batches of real-world Suhuang Zhike Capsules dry extract powder and granules intermediates as the research object. Firstly, a method for testing the physical properties of Suhuang Zhike Capsules powder and granules with 19 physical indicators was established. The results showed that the granules of dry extract powder after granulation had a smaller particle size, wider particle size distribution range and poor fluidity, which easily caused the problem of over-limit capsule loading. Secondly, correlation analysis, principal component analysis and cluster analysis were used for mathematical statistics. The correlation analysis showed that the density of dry extract powder could affect the chroma and fluidity. At the same time, the particle size in the granules had a stronger effect on the chroma and fluidity than the density. The study also found that the particle size and hygroscopicity of dry extract powder were potentially key physical properties that affected the physical properties of granules. Furthermore, the results of principal component analysis and cluster analysis showed that the consistency of the physical properties between the dry extract powder and intermediate granules was relatively poor. To this end, similarity analysis was carried out, and the quality control method of powder and granules based on physical fingerprint was established. The results showed that the physical fingerprint similarity of 25 batches of dry extract powder was 0.639-0.976, and the physical fingerprint similarity of the gra-nules was 0.716-0.983. With the similarity of 0.85 as the threshold, the batches with abnormal physical properties could be identified. In this study, the process quality control method of Suhuang Zhike Capsules based on the physical properties of powder and granules was established finally, which realized the identification of abnormal batches, and provided a reference for the process quality control of Suhuang Zhike Capsules.

[Critical quality attribute assessment of big brand traditional Chinese medicine: online NIR quality control research on boiling time during extraction process].

Assessment of the status property(boiling time) is a challenge for the quality control of extraction process in pharmaceutical enterprises. In this study, the pilot extraction process of Phellodendron chinense was used as the research carrier to develop an online near-infrared(NIR) quality control method based on the status property(boiling time). First, the NIR spectra of P. chinense were collected during the two pilot-scale extraction processes, and the status property(boiling time) was assessed by observing the state of bubbles in the extraction tank using a transparent window during the extraction process, which was then used as a reference standard. Based on the moving block standard deviation(MBSD) algorithm, the assessment model using online NIR spectra for boiling time during extraction process was established. In addition, the model was optimized as follows: standard normal variable(SNV) for spectral pretreatment, modeling band of 800-2 200 nm, and window size of 4. The results showed that, with 0.002 0 as the MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process. Furthermore, the principal component analysis-moving block standard deviation(PCA-MBSD) model was developed by our group to reduce the influence of online NIR spectral noise and background signal on the model, and the number of principal components was optimized into 2 in the PCA-MBSD model. The results showed that, with 0.000 075 as the PCA-MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process, with improved reliability. This study can provide a assessment method for boiling time during extraction process using online NIR spectra, which can replace the empirical judgment in manual observation, and realize the digitalization of the extraction process for big brand traditional Chinese medicine.

Evaluation of origanum oil, hydrolysable tannins and tea saponin in mitigating ruminant methane: In vitro and in vivo methods.

The objective of this study was to investigate the effects of origanum oil (ORO), hydrolysable tannins (HYT) and tea saponin (TES) on methane (CH4 ) emission, rumen fermentation, productive performance and gas exchange in sheep by using in vitro and in vivo methods. The ORO, HYT and TES additive levels were normalized per kg dry matter (DM) in both in vitro and in vivo experiments: ORO-0, 10, 20 and 40 ml/kg; HYT-0, 15, 30 and 60 g/kg; and TES-0, 15, 30 and 60 g/kg, respectively. During in vitro incubation, 40 ml/kg ORO linearly decreased CH4 emission (p < 0.05); 20 and 40 ml/kg ORO cubically decreased carbon dioxide (CO2 ) production (p < 0.05), and rumen pH was cubically raised with the increasing ORO additive level (p < 0.01). The 60 g/kg HYT cubically decreased CH4 production (p < 0.05). The pH of 60 g/kg HYT was higher than that of 15 and 30 g/kg (p < 0.01); the pH of 20 g/kg TES was higher than that of 5 g/kg (p < 0.05). In the in vivo experiments, 40 ml/kg ORO inhibited dry matter intake (p < 0.01) cubically and reduced average daily gain (ADG) and feed conversion ratio (FCR) cubically (p < 0.05), and 20 or 40 ml/kg ORO linearly decreased CH4 production based on per day or metabolic weight (W0.75 ) (p < 0.05). Both 30 and 60 g/kg HYT linearly inhibited CH4 emission on the bases of per day and W0.75 (p < 0.05). The 20 g/kg TES improved the apparent digestibility of crude protein (p < 0.05), 10 and 20 g/kg of TES decreased CH4 emission (p < 0.05), and 5 g/kg of TES reduced O2 consumption and CO2 production (p < 0.05). In conclusion, these three plant extracts all showed the abilities on mitigating CH4 emission of sheep with appropriate additive ranges.

A rapid analysis method of safflower (Carthamus tinctorius L.) using combination of computer vision and near-infrared.

The quality of safflower (Carthamus tinctorius L.) in the market is uneven due to the problems of dyeing and adulteration of safflower, and there is no perfect standard for the classification of quality grade of safflower at present. In this study, computer vision (CV) and near-infrared (NIR) were combined to realize the rapid and nondestructive analysis of safflower. First, the partial least squares discrimination analysis (PLS-DA) model was used to qualitatively identify the dyed safflower from 150 samples. Then the partial least squares (PLS) model was used for quantitative analysis of the hydroxy safflower yellow pigment A (HSYA) and water extract of undyed safflower. Herein, the discrimination rate of PLS-DA model reached 100%, and the residual predictive deviation (RPD) values of the PLS models for HSYA and water extract were 2.5046 and 5.6195, respectively. It indicated that the rapid analysis method combining CV and NIR was reliable, and its results can provide important reference for the formulation of safflower quality classification standards in the market.

Micromotors for Active Delivery of Minerals toward the Treatment of Iron Deficiency Anemia.

As the most common nutritional disorder, iron deficiency represents a major public health problem with broad impacts on physical and mental development. However, treatment is often compromised by low iron bioavailability and undesired side effects. Here, we report on the development of active mineral delivery vehicles using Mg-based micromotors, which can autonomously propel in gastrointestinal fluids, aiding in the dynamic delivery of minerals. Iron and selenium are combined as a model mineral payload in the micromotor platform. We demonstrate the ability of our mineral-loaded micromotors to replenish iron and selenium stores in an anemic mouse model after 30 days of treatment, normalizing hematological parameters such as red blood count, hemoglobin, and hematocrit. Additionally, the micromotor platform exhibits no toxicity after the treatment regimen. This proof-of-concept study indicates that micromotor-based active delivery of mineral supplements represents an attractive approach toward alleviating nutritional deficiencies.