The use of protein stains to enhance fingermark ridge detail in blood is a common technique used by forensic practitioners around the world. Amido Black is one of the most favoured protein stains due to its strong staining ability. The most common formulation of Amido Black is methanol based, with an ability to simultaneously fix and stain the blood impression, however methanol is toxic and can disrupt some surfaces, potentially compromising fingermark detail. If the surface is suspected of being a material that is impacted by methanol, there is an alternative aqueous formulation, which requires a fixative step to set the blood prior to staining so as not to wash away potential ridge detail. The multi-step process of aqueous protein stains is tedious and numerous studies have been conducted to improve the formula to achieve a combined fixing/staining solution that performs like the methanolic reagent. A combined fixative and stain formulation of aqueous based Amido Black was compared to a multi-step formulation with a separate sulfosalicylic acid fixative. Of the 243 split fingermark impressions analysed the majority (63.5 %) showed no preference to either treatment, with a marginally greater proportion of the remaining marks slightly favouring the combined fixative and stain formulation. Given that the new combined formulation performed broadly similarly to the existing multi step formulation, the potential time savings of this simpler approach may be beneficial to implement into operational use.

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are attractive drug targets for cancer immunotherapy. After disappointing results of the epacadostat as a selective IDO inhibitor in phase III clinical trials, there is much interest in the development of the TDO selective inhibitors. In the current study, several data analysis methods and machine learning approaches including logistic regression, Random Forest, XGBoost and Support Vector Machines were used to model a data set of compounds retrieved from ChEMBL. Models based on the Morgan fingerprints revealed notable fragments for the selective inhibition of the IDO, TDO or both. Multiple fragment docking was performed to find the best set of bound fragments and their orientation in the space for efficient linking. Linking the fragments and optimization of the final molecules were accomplished by means of an artificial intelligence generative framework. Finally, selectivity of the optimized molecules was assessed and the top 4 lead molecules were filtered through PAINS, Brenk and NIH filters. Results indicated that phenyloxalamide, fluoroquinoline, and 3-bromo-4-fluroaniline confer selectivity towards the IDO inhibition. Correspondingly, 1-benzyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione was found to be an integral fragment for the selective inhibition of the TDO by constituting a coordination bond with the Fe atom of heme. In addition, furo[2,3-c]pyridine-2,3-diamine was found as a common fragment for inhibition of the both targets and can be used in the design of the dual target inhibitors of the IDO and TDO. The new fragments introduced here can be a useful building blocks for incorporation into the selective TDO or dual IDO/TDO inhibitors.

BACKGROUND: YiXinShu capsule (YXSC), originally from the classical TCM formula named \"Sheng-Mai-San\", has been extensively utilized in clinic for the treatment of cardiovascular diseases. However, there were few reports about the quality assessment of YXSCs both internationally and domestically.
OBJECTIVE: The objective was to develop a multi-strategy platform incorporating systematic quantitative fingerprint analysis and antioxidant activity determination, with chemometric analysis and bivariate correlation analysis as the auxiliary approaches, to assess and monitor the quality of YXSCs.
METHODS: Firstly, according to the Chinese Pharmacopoeia (2020 edition), 12 key indicator components from seven herb medicines were quantified by HPLC method. Then, three-dimensional fingerprints comprising five-wavelength fusion fingerprint (FWF-FP), electrochemical fingerprint (EC-FP) and Differential Scanning Calorimetry fingerprint (DSC-FP) were established to assess and monitor YXSCs using systematically quantified fingerprint method (SQFM) and principal component analysis (PCA). Moreover, by integrating the analysis of the three-dimensional fingerprints, the quality of YXSCs from different batches was effectively screened. Finally, the antioxidant activity of this TCM was assessed through DPPH and ABTS methods, and the L-ascorbic acid equivalent antioxidant capacity (AEAC) values were compared to evaluate the antioxidant activities of the two methods. A Partial Least Squares (PLS) model was used to develop the spectrum-activity relationship between FWF-FP and AEAC, and a bivariate correlation analysis (BCA) was used to assess the correlation between FWF-FP and EC-FP.
RESULTS: The key indexes including tanshinone I, tol, toe, Atp, first exothermic peak, and second exothermic peak can differentiate between various batches of YXSCs based on their three-dimensional fingerprint profiles. The integration evaluation results from 42 batches of YXSCs were categorized into 2-5 grades, indicating good quality consistency across different batches. In vitro studies have indicated a significant antioxidant activity capacity of YXSCs. The PLS model revealed that 37 out of the 41 fingerprint peaks exhibited antioxidant activity. The overall trend of BCA was consistent with PLS model results.
CONCLUSIONS: This research presents a scientific and holistic strategy for the quality consistency evaluation of YXSCs, thereby offering an effective approach for the thorough evaluation of TCMs.

This paper aims to study the spectrum-effect relationship between the fingerprints before and after salt processing of Dipsacus asper and the efficacy of warming and tonifying kidney Yang and find the main active components against kidney Yang deficiency before and after salt processing of D. asper, so as to provide the basis for clarifying the effect of salt processing on kidney Yang deficiency. The HPLC fingerprint before and after salt processing of D. asper was established by the HPLC-DAD. 15 common peaks were obtained, and 11 components were identified. The content changes of various components in rat serum were detected, and the difference in efficacy before and after salt processing was compared. The results of pharmacological experiments showed that salt processing of D. asper could enhance the kidney index. At the same dose, there was a significant difference between the raw D. asper and D. asper after salt processing groups. Compared with the model group, the contents of ACTH, cAMP, CORT, E_2, GH, Na~+-K~+-ATPase, T, and T4 in the serum of rats in the administration group increased to a certain extent, and the contents of cGMP and TNF-α decreased to a certain extent. Among them, there were significant differences in the above indexes in the serum of rats in the high-dose group of raw D. asper, middle-dose group of D. asper after salt processing, high-dose group of D. asper after salt processing, and the positive drug group. The overall results showed that D. asper after salt processing was more effective than raw D. asper in preventing kidney yang deficiency. The efficacy of D. asper was evaluated by grey correlation analysis, entropy method, and Pearson correlation analysis, and the components of D. asper after salt processing against kidney yang deficiency were screened out. According to the results of correlation degree ranking, the components with increased ranking before and after salt processing of D. asper were loganin, chlorogenic acid, dipsacoside A, asperosaponin Ⅵ, caffeic acid, and isochlorogenic acid B. It was preliminarily speculated that these compounds may be the potential pharmacodynamic components for the treatment of kidney yang deficiency before and after salt processing of D. asper. The changing components before and after the salt processing of D. asper were determined, which proved that D. asper after salt processing was superior to D. asper in the treatment of kidney yang deficiency. The spectrum-effect relationship between the efficacy of D. asper before and after salt processing and the treatment of kidney yang deficiency was established, which laid a foundation for the subsequent study on the pharmacodynamic components and molecular mechanism of salt processing of D. asper.

UNASSIGNED: Liuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP.
UNASSIGNED: LGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated.
UNASSIGNED: The results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity.
UNASSIGNED: The results of present study would be of help to gain the understanding of structure-activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.

This study demonstrated the correlation of molecular structures of Peroxisome proliferator-activated receptor gamma (PPARγ) modulators and their biological activities. Bayesian classification, and recursive partitioning (RP) studies have been applied to a dataset of 323 PPARγ modulators with diverse scaffolds. The results provide a deep insight into the important sub-structural features modulating PPARγ. The molecular docking analysis again confirmed the significance of the identified sub-structural features in the modulation of PPARγ activity. Molecular dynamics simulations further underscored the stability of the complexes formed by investigated modulators with PPARγ. Overall, the integration of many computational approaches unveiled key structural motifs essential for PPARγ modulatory activity that will shed light on the development of effective modulators in the future.

Predicting compound-induced inhibition of cardiac ion channels is crucial and challenging, significantly impacting cardiac drug efficacy and safety assessments. Despite the development of various computational methods for compound-induced inhibition prediction in cardiac ion channels, their performance remains limited. Most methods struggle to fuse multi-source data, relying solely on specific dataset training, leading to poor accuracy and generalization. We introduce MultiCBlo, a model that fuses multimodal information through a progressive learning approach, designed to predict compound-induced inhibition of cardiac ion channels with high accuracy. MultiCBlo employs progressive multimodal information fusion technology to integrate the compound\'s SMILES sequence, graph structure, and fingerprint, enhancing its representation. This is the first application of progressive multimodal learning for predicting compound-induced inhibition of cardiac ion channels, to our knowledge. The objective of this study was to predict the compound-induced inhibition of three major cardiac ion channels: hERG, Cav1.2, and Nav1.5. The results indicate that MultiCBlo significantly outperforms current models in predicting compound-induced inhibition of cardiac ion channels. We hope that MultiCBlo will facilitate cardiac drug development and reduce compound toxicity risks. Code and data are accessible at: https://github.com/taowang11/MultiCBlo. The online prediction platform is freely accessible at: https://huggingface.co/spaces/wtttt/PCICB.

Background Fingertip injuries with volar pulp tissue defects present a significant challenge in management. This study aimed to evaluate the efficacy of a conservative treatment protocol using artificial dermis and semi-occlusive dressings for these injuries. Methods A single-center, prospective study was conducted on 31 patients with fingertip injuries involving volar pulp defects. The treatment protocol included wound debridement, application of artificial dermis (Pelnac®), and a semi-occlusive dressing (IV3000®). The outcomes were assessed using subjective questionnaires and objective measures, including fingerprint regeneration, sensory function, pain, and cosmetic appearance. Results The mean treatment duration was 45.29 days (SD = 17.53). Complications were minimal, with only one case (3.22%) directly attributable to the treatment. Fingerprint regeneration was considerable (mean score = 2.58, SD = 0.67). The sensory disturbances were minimal, with no significant differences across injury types. Post-treatment pain was low (mean = 0.45, SD = 0.67), and cosmetic satisfaction was high (mean = 4.09, SD = 0.94). The overall patient satisfaction was high (mean = 4.41, SD = 0.67), regardless of injury severity. Conclusions The conservative treatment protocol using artificial dermis and semi-occlusive dressings is a promising strategy for managing fingertip injuries with volar pulp defects. This approach minimizes surgical morbidity and achieves excellent functional and aesthetic outcomes.

Quisqualis fructus (QF) is a traditional Chinese medicine (TCM) that it has a long history in the therapeutic field of killing parasites, eliminating accumulation, and stopping diarrhea. However, the therapeutic material basis of QF is remaining ambiguous nowadays. The geographical origin differences of QF are also usually ignored in the process of medication. In this study, the alcohol-aqueous soluble constituents in QF from different origins were systematically characterized and accurately measured by ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography (HPLC) respectively. Chemometric analysis was performed for origin differentiation and screening of potential quality marker (Q-marker). Finally, A total of 106 constituents were tentatively characterized in positive and negative ion modes, including 29 fatty acids, 26 organic acids, 11 amino acids and derivatives, 10 glycosides, 9 alkaloids and derivatives, and 21 other constituents. QF from different origins were effectively distinguished and 16 constituents were selected as the potential Q-markers subsequently. Four representative components (trigonelline, adenosine, ellagic acid, and 3,3\'-di-O-methylellagic acid) in QF samples were simultaneously determined. HPLC fingerprint analysis indicated that the similarity between 16 batches of QF was in the range of 0.870-0.999. The above results provide some insights for the research on the pharmacodynamic constituents, quality control, and geographical discrimination of QF.

Litchi chinensis Sonn (Litchi) has been listed in the Chinese Pharmacopeia, and is an economically and medicinally valuable species within the family Sapindaceae. However, the material basis of its pharmacological action and the pharmacodynamic substances associated with its hypoglycemic effect are still unclear. The predominant objective of this study was to establish the fingerprint profile of litchi leaves and to evaluate the relationship between the components of the high-performance liquid chromatography (HPLC) fingerprint of litchi leaves, assess its hypoglycemic effect by measuring α-glucosidase and α-amylase inhibition, and find the spectrum-effect relationship of litchi leaves by bivariate correlation analysis, Grey relational analysis and partial least squares regression analysis. In this study, the fingerprint of litchi leaves was established by HPLC, and a total of 15 common peaks were identified that clearly calibrated eight components, with P1 being gallic acid, P2 being protocatechuic acid, P3 being catechin, P6 being epicatechin, P12 being rutin, P13 being astragalin, P14 being quercetin and P15 being kaempferol. The similarities between the fingerprints of 11 batches of litchi leaves were 0.766-0.979. Simultaneously, the results of the spectrum-effect relationship showed that the chemical constituents represented by peaks P8, P3, P12, P14, P2, P13, and P11 were relevant to the hypoglycemic effect.