Novel sodium tauroursodeoxycholate-based multifunctional liposomal delivery system for encapsulation of oleanolic acid and combination therapy of type 2 diabetes mellitus.

Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy.

Impacts of compatibility between rainwater availability and water demand on water saving performance of rainwater harvesting systems.

Rainwater Harvesting Systems (RHS) are widely implemented to mitigate urban water shortages, yet the impacts of compatibility between rainwater availability and water demand on their performance are often overlooked. This study introduces novel rainwater deficit and surplus indices to quantitatively assess the impacts of compatibility between rainwater availability and water demand on the performance of RHS across 16 cities in different climate zones and under 3 daily water demand scenarios. The rainwater deficit and surplus indices, and the water saving efficiency and reliability of RHS are calculated based on long-term (1991-2020) continuous simulations using a daily water balance model. Results show the rainwater deficit index effectively quantifies water supply pressure on RHS, while the rainwater surplus index quantitatively evaluates their water saving potential. Both of water saving efficiency and reliability of RHS significantly linearly decrease with the rainwater deficit index (P < 0.05), and the coefficients of determination (R2) decrease from 0.96 to 0.80 as tank size increases from 1 to 300 m3. Both of water saving efficiency and reliability increase along sigmoid curves with the rainwater surplus index (P < 0.05), and R2 values increase from 0.91 to 0.99 with tank size. The results indicate that tank size optimization enhances water saving performance of RHS through reducing deficits and surpluses. However, the performance enhancement by tank size optimization could be limited by the compatibility between rainwater availability and water demand. Taken Kashgar (arid climate) as an example, the thresholds of water saving efficiency under all water demand scenarios are below 15% due to high rainwater deficit and low surplus. This study emphasizes that the compatibility between rainwater availability and water demand should be considered in planning and design of RHS.

Topical Delivery of Dual Loaded Nano-Transfersomes Mediated Chemo-Photodynamic Therapy against Melanoma via Inducing Cell Cycle Arrest and Apoptosis.

Melanoma is a malignant skin cancer associated with high mortality rates and drug resistance, posing a significant threat to human health. The combination of chemotherapy and photodynamic therapy (PDT) represents a promising strategy to enhance antitumor efficacy through synergistic anti-cancer effects. Topical delivery of chemotherapeutic drugs and photosensitizers (PS) offers a non-invasive and safe way to treat melanoma. However, the effectiveness of these treatments is often hindered by challenges such as limited skin permeability and instability of the PS. In this study, transfersomes (TFS) were designed to facilitate transdermal delivery of the chemotherapeutic drug 5-Fluorouracil (5-FU) and the PS Imperatorin (IMP) for combined chemo-photodynamic therapy for melanoma. The cytotoxic and phototoxic effects of TFS-mediated PDT (TFS-UVA) were investigated in A375 cells and nude mice. The study also demonstrated that TFS-UVA generated intracellular ROS, induced G2/ M phase cell cycle arrest, and promoted cell apoptosis. In conclusion, this study indicated that 5-FU/ IMP-TFS serves as an effective transdermal therapeutic strategy for chemo-PDT in treating melanoma.

KMT2D deficiency leads to cellular developmental disorders and enhancer dysregulation in neural-crest-containing brain organoids.

KMT2D, a H3K4me1 methyltransferase primarily regulating enhancers, is a leading cause of KABUKI syndrome. This multisystem disorder leads to craniofacial and cognitive abnormalities, possibly through neural crest and neuronal lineages. However, the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown. Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation. To pinpoint KMT2D's enhancer target, we developed a genome-wide cis-regulatory element explorer (GREE) based on single-cell multiomic integration. Single cell RNA-seq revealed that KMT2D-knockout (KO) and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction. Mechanistically, GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer, providing the microenvironment for neural crest and neuronal development. Interestingly, KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate, indicating impaired niche cell function. Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion, emphasizing the WNT3A enhancer as the predominant target of KMT2D. Conversely, reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment. Overall, our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype.

Deciphering the Effect of Defect Dipoles on the Polarization and Electrostrain Behavior in Perovskite Ferroelectrics.

Defect dipoles are crucial for regulating electromechanical properties in piezoelectric ceramics, but their effects on polarization and electrostrain behaviors are still unclear. Here, a reasonable theoretical model is proposed and evidenced by experiments to address a long-standing puzzle of the relationship between the internal bias field and defect dipoles. By incorporating the additional polarization induced by defect dipoles, we refine the classical theory to account for the recently reported asymmetric giant-strain behaviors. Phase-field simulation reveals the electrostrain evolution in response to defect dipole elastic distortion and additional polarization. This work not only elucidates the effect of defect dipoles on polarization and electrostrain but also advances the theoretical understanding of defects in piezoelectrics.

Defect dipole stretching enables ultrahigh electrostrain.

Piezoelectric actuators have been extensively utilized as micro-displacement devices because of their advantages of large output displacement, high sensitivity, and immunity to electromagnetic interference. Here, we propose a straightforward approach to design <110>-oriented defect dipoles by introducing A-site vacancies and oxygen vacancies in (K0.48Na0.52)0.99NbO2.995 ceramics. As a result, we achieve ultrahigh electrostrains of 0.7% at 20 kV cm-1 (with an effective piezoelectric strain coefficient d33* = 3500 pm V-1), outperforming the performance of existing piezoelectric ceramics at the same driving field. The exceptional electrostrain is primarily attributed to the large stretching of defect dipoles when subjected to an applied electric field, a phenomenon that has been experimentally confirmed. Moreover, the strong interaction between these defect dipoles and <110> spontaneous polarizations plays a critical role in minimizing hysteresis and ensuring excellent fatigue resistance. Our findings present a practical and effective strategy for developing high-performance piezoelectric materials tailored for advanced actuator applications.

Efficacy and Safety of Remimazolam Versus Etomidate for Induction of General Anesthesia: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are "randomized controlled trials," "etomidate," and "remimazolam." The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. TRIAL REGISTRATION: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55948.

Ultrahigh Electrobending Deformation in Lead-Free Piezoelectric Ceramics via Defect Concentration Gradient Design.

Recent breakthroughs in defect-engineered lead-free piezoelectric ceramics have reported remarkable electrostrain values, surpassing the limit of lattice distortion. This has aroused wide concern on bending deformation and the associated underlying mechanism. Herein, via designing lead-free piezoelectric ceramics with varying volatilization characteristics, it is uncovered that the ultrahigh electrobending deformation is primarily attributed to a large strain gradient induced by unevenly distributed defect dipoles. In 0.5 mm thick Sr/Sn co-doped potassium sodium niobate ceramics featuring volatile K/Na elements, the inherent bipolar electrostrain value can reach 0.3% at 20 kV cm-1 due to the existence of defect dipoles, while the gradient distribution of defect dipole generates significant bending displacement, amplifying apparent electrostrain value to 1.1%. Notably, nonvolatile Ba0.99TiO2.99 ceramic with homogeneous defect dipole distribution does not present electrobending. Of particular interest is that the electrobending phenomenon can be observed through introducing a defect dipole gradient into barium titanate ceramic. A monolayer ceramic with defect dipole gradient can generate large tip displacement (±1.5 mm) in cantilever structure, demonstrating its promising potential in precise positioning. This study delves into the underlying mechanism driving electrobending deformation and its impact on the apparent electrostrain measurement in defect-engineered piezoelectric ceramics, providing fresh perspectives for the development of piezoelectric bending actuators.

The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

Therapeutic effects of tetrandrine in inflammatory diseases: a comprehensive review.

Inflammation can be triggered by any factor. The primary pathological manifestations can be summarized as the deterioration, exudation, and proliferation of local tissues, which can cause systemic damage in severe cases. Inflammatory lesions are primarily localized but may interact with body systems to cause provocative storms, parenchymal organ lesions, vascular and central nervous system necrosis, and other pathologic responses. Tetrandrine (TET) is a bisbenzylquinoline alkaloid extracted from the traditional Chinese herbal medicine Stephania tetrandra, which has been shown to have significant efficacy in inflammatory conditions such as rheumatoid arthritis, hepatitis, nephritis, etc., through NF-κB, MAPK, ERK, and STAT3 signaling pathways. TET can regulate the body's imbalanced metabolic pathways, reverse the inflammatory process, reduce other pathological damage caused by inflammation, and prevent the vicious cycle. More importantly, TET does not disrupt body's normal immune function while clearing the body's inflammatory state. Therefore, it is necessary to pay attention to its dosage and duration during treatment to avoid unexpected side effects caused by a long half-life. In summary, TET has a promising future in treating inflammatory diseases. The author reviews current therapeutic studies of TET in inflammatory conditions to provide some ideas for subsequent anti-inflammatory studies of TET.

Therapeutic effects and molecular mechanisms of natural products in thrombosis.

Thrombotic disorders, such as myocardial infarction and stroke, are the leading cause of death in the global population and have become a health problem worldwide. Drug therapy is one of the main antithrombotic strategies, but antithrombotic drugs are not completely safe, especially the risk of bleeding at therapeutic doses. Recently, natural products have received widespread interest due to their significant efficacy and high safety, and an increasing number of studies have demonstrated their antithrombotic activity. In this review, articles from databases, such as Web of Science, PubMed, and China National Knowledge Infrastructure, were filtered and the relevant information was extracted according to predefined criteria. As a result, more than 100 natural products with significant antithrombotic activity were identified, including flavonoids, phenylpropanoids, quinones, terpenoids, steroids, and alkaloids. These compounds exert antithrombotic effects by inhibiting platelet activation, suppressing the coagulation cascade, and promoting fibrinolysis. In addition, several natural products also inhibit thrombosis by regulating miRNA expression, anti-inflammatory, and other pathways. This review systematically summarizes the natural products with antithrombotic activity, including their therapeutic effects, mechanisms, and clinical applications, aiming to provide a reference for the development of new antithrombotic drugs.

High-Performance All-Textile Triboelectric Nanogenerator toward Intelligent Sports Sensing and Biomechanical Energy Harvesting.

Merging textiles with advanced energy harvesting technology via triboelectric effects brings novel insights into self-powered wearable textile electronics. However, fabrication of a comfortable textile-based triboelectric nanogenerator (TENG) with high outputs remains challenging. Herein, we propose a highly flexible, tailorable, single-electrode all-textile TENG (t-TENG) with both wear comfort and high outputs. A dielectric modulated porous composite coating containing poly(vinylidene fluoride)-hexafluoropropylene copolymer and barium titanate nanoparticles is constructed on conductive fabric to counterpart with highly positive glass fiber fabric through knotted yarn bonding, maintaining the superiority of textiles and strong triboelectricity. Through the synergistic optimization of charge storage via dielectric modulation and charge dissipation offset by electrical poling, remarkable outputs (261 V, 1.5 µA, and 12.7 nC) are obtained from a miniaturized, lightweight t-TENG (2 × 2 cm2, 130 mg) with an instantaneous power density of 654.48 mW·m-2, as well as excellent electrical robustness and device durability over 20,000 cycles. The t-TENG also exhibits a high sensitivity of 3.438 V·kPa-1 in the force region (1-10 N), demonstrating great potential in TENG-based intelligent sports sensing applications for monitoring and correcting the basketball shooting hand and foot arch posture. Furthermore, over 110 light-emitting diode arrays can be lightened up by gently tapping this miniaturized t-TENG. It also offers a wearable power source scheme through integrating the single-electrode device into clothing and utilizing the skin as the grounded electrode, revealing its ease of integration and biomechanical energy harvesting capability. This work provides an attractive paradigm for next-generation textile electronics with well-balanced device performance and wear comfort.

Design and hydrologic performance estimation of highway filter drains using a novel analytical probabilistic model.

Sustainable drainage systems (SuDS) are nature-based methods of managing urban stormwater runoff. Although they are widely used, some SuDS, such as highway filter drains (HFDs), are understudied with respect to sizing and performance. For the first time, we developed an analytical probabilistic model (APM) that can be used to design and estimate the hydrologic performance of HFDs. Unlike the conventionally used design-storm based or continuous simulation approaches, our APM can directly calculate the runoff capture ratios of HFDs using closed-form analytical equations. Validation of the APM presented here shows that it is robust and reliable. The relative differences between the APM-estimated and continuous simulation-determined runoff capture ratios for all the simulated design cases are less than 8.5%.

Superior Electromechanical Compatibility in Lead-Free Piezoceramics with Mobile Transition-Metal Defects.

Donor and acceptor ions serving as extrinsic defects in piezoelectrics are mostly used to improve the performance merits to satisfy the industrial application. However, the conventional doping strategy is unable to overcome the inherent trade-off between the piezoelectric coefficient (d33) and mechanical quality factor (Qm). Herein, inspired by the valence state variation observed in manganese oxides during sintering, this study focuses on manipulating intrinsic oxygen vacancies and extrinsic manganese defects in potassium sodium niobate (KNN) ceramics via heat treatment. The annealing process results in a simultaneous improvement in both d33 (20%) and Qm (80%), leading to comparable performance with commercial PZT-5A ceramics and enabling their application in atomizer components. Moreover, the mechanism of manganese occupation and diffusion is proposed by an extended X-ray absorption fine structure and density functional theory analysis. The improved electromechanical performance in the annealed KNN ceramic is associated with the optimized redistribution of acceptor and donor manganese defects, which is facilitated by the recombination of oxygen vacancies. This work breaks longstanding obstacles in comprehending the existing forms of manganese in KNN and offers potential in popularizing KNN-based piezoceramics to replace traditional PZT lead-based counterparts in the industrial market.

Characterization of Anxiety-Like Behaviors and Neural Circuitry following Chronic Moderate Noise Exposure in Mice.

BACKGROUND: Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. OBJECTIVES: We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. METHODS: Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. RESULTS: Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the MG→LA or ACx→LA circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. DISCUSSION: Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532.

The improved analytical stochastic model of infiltration trenches for stormwater quantity control.

As one of the infiltration-based low-impact development (LID) measures, infiltration trenches are widely used to reduce runoff and improve water quality. The conventional analytical stochastic approach developed for use in the hydrologic design of infiltration trenches often overestimates the trench's runoff reduction performance when the infiltration rate at the bottom of the trench exceeds some high level or when the size of the trench is smaller than some threshold level. Furthermore, the appropriateness of using kernel density estimation (KDE) for rainfall event separation and frequency analysis has not been examined yet in the actual hydrologic design of LIDs. To overcome these deficiencies, an improved analytical stochastic model (ASM) was developed in this study incorporating the KDE-based rainfall event characterization and a modified formula for estimating the effective storage capacity of trenches. The calibration, verification and application of the improved ASM were systematically presented and their results were discussed. The accuracy of the improved ASM were verified by comparing the analytical results against the corresponding continuous simulation results. A large number of design cases in nine provincial capital cities of China were analyzed using the improved ASM and considering the effects of soil types, trench's storage reservoir depth, area ratio, and climate conditions. The improved ASM of infiltration trenches is useful for quickly and accurately assessing their water quantity control performances. The results indicated that the accuracy of improved ASM improved by up to 71 % in terms of R-square among the 9 study areas compared to conventional ASM. The improved ASM can be used to directly and quickly calculate the useful hydrologic performance indices for a given trench size, soil condition, area ratio and local climate condition, it can thus provide scientific guidance for the Sponge City construction in China and sustainable urban stormwater management.

Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

Exploring the Catalytic Flexibility and Reversibility of Plant Glycosyltransferase HtUGT72AS1 for Glycodiversification of Phenolic Compounds.

Plant bioactive metabolites such as flavonoids are usually present in glycosylated forms by the attachment of various sugar groups. In this study, a catalytically flexible and reversible glycosyltransferase (HtUGT72AS1) was cloned and characterized from Helleborus thibetanus. HtUGT72AS1 could directly accept six sugar donors (UDP-glucose/-arabinose/-galactose/-xylose/-N-acetylglucosamine/-rhamnose) to catalyze the 3-OH glycosylation of flavonols. It also catalyzed the 4' and 7-OH glycosylation of other types of flavonoids, which lacked the 3-OH group. Additionally, the HtUGT72AS1-catalyzed reaction was highly reversible when using 2-chloro-4-nitrophenyl glycosides as substrates, which could be used for one-pot or coupled production of bioactive glycosides. It is the first reported UGT for the synthesis of arabinosides and galactosides using a transglycosylation platform. Based on structural modeling and mutagenetic analysis, the mutation of Tyr377 to Ara enhanced the catalytic efficiency of HtUGT72AS1 toward UDP-N-acetylglucosamine, and the V146S mutant gained an improvement in the regioselectivity toward 7-OH of flavonoids.

Performance evaluation of E-nose and E-tongue combined with machine learning for qualitative and quantitative assessment of bear bile powder.

Bear bile powder (BBP) is a valuable animal-derived product with a huge adulteration problem on market. It is a crucially important task to identify BBP and its counterfeit. Electronic sensory technologies are the inheritance and development of traditional empirical identification. Considering that each drug has its own specific odor and taste characteristics, electronic tongue (E-tongue), electronic nose (E-nose) and GC-MS were used to evaluate the aroma and taste of BBP and its common counterfeit. Two active components of BBP, namely tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) were measured and linked with the electronic sensory data. The results showed that bitterness was the main flavor of TUDCA in BBP, saltiness and umami were the main flavor of TCDCA. The volatiles detected by E-nose and GC-MS were mainly aldehydes, ketones, alcohols, hydrocarbons, carboxylic acids, heterocyclic, lipids, and amines, mainly earthy, musty, coffee, bitter almond, burnt, pungent odor descriptions. Four different machine learning algorithms (backpropagation neural network, support vector machine, K-nearest neighbor, and random forest) were used to identify BBP and its counterfeit, and the regression performance of these four algorithms was also evaluated. For qualitative identification, the algorithm of random forest has shown the best performance, with 100% accuracy, precision, recall and F1-score. Also, the random forest algorithm has the best R2 and the lowest RMSE in terms of quantitative prediction.