G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

The traditional commodity specifications of Chinese medicinal materials are mainly divided into different grades based on macroscopic characteristics. As the basis for high quality and good price, there is still a lack of systematic evaluation on whether they are consistent with the current standards and whether they can reflect the internal quality of medicinal material. Panax notoginseng is a commonly used, large consumption of Chinese medicinal material. At present, it is divided into 8 grades in the market based on "Tou" (the number of crude drug /500 g), but it is not related to the standard of total saponins of Panax notoginseng (the sum of three saponins) in Chinese Pharmacopoeia. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with mass spectrometry molecular network were used for the rapid identification of saponins of Panax notoginseng with different "Tou" and a total of 64 saponins were identified. Seventeen saponins related to "Tou" were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). The content of five saponins R₁, Rb₁, Rg₁, Rd, and Re in Panax notoginseng with different "Tou" was determined by high performance liquid chromatography (HPLC). The results of correlation analysis showed that Rd and R₁ with the largest VIP values among the differential saponins, which significantly negatively correlated with "Tou" (P < 0.05). Based on the determination results of 36 batches of samples, using Rd/Total Panax notoginseng saponins (TPNS) ratio ( > 0.08) as the index, Panax notoginseng can be divided into two grades: 20-60 "Tou" (superior) and 80-200 "Tou" (qualified). Based on the concept of "macroscopic characteristics and chemical profiling", this study integrates the non-targeted analysis and quantitative determination methods to provide a new strategy for quality evaluation of Panax notoginseng.

In order to study the compounds from Glechoma longituba (Nakai) Kupr. and explore the substance bases of its dissipating blood stasis, MCI, silica gel, Sephadex LH-20, ODS column chromatography and preparative thin layer chromatography were used to isolate and purify the compounds. The structures were identified by MS, 1D NMR, and 2D NMR spectra analysis, etc. Eight triterpenoids were isolated from dichloromethane fraction of ethanol extract from G. longituba and identified as 2α,3α,16β-trihydroxy-13α,27-cyclours-11-en-28-oic acid (1), 28-norurs-12-ene-3β,17β-diol (2), 28-norolean-12-ene-3β,17β-diol (3), oleanonic acid (4), 3β,13β-dihydroxyurs-11-en-28-oic acid (5), uvaol (6), oleanolic acid (7), ursolic acid (8). Compound 1 is a new hexacyclic triterpene with 13α,27-cyclopropane structure, named euscaphic acid H; compounds 2 and 3 were isolated from Lamiaceae for the first time while compounds 4 and 5 were isolated from this genus. The in vitro anticoagulant activity of triterpenoids was evaluated by four coagulation indexes (activated partial thromboplastin time, APTT; thrombin time, TT; prothrombin time, PT; fibrinogen, FIB). Among them, compounds 1 and 6 showed obvious anticoagulant effects.

Phellodendri Chinensis Cortex (PCC) featured with thick cortex and bright-yellow is considered to be of high quality according to traditional appearance traits evaluation mode. However, the correlation between appearance traits and internal quality of PCC has not been scientifically revealed. Here, based on the theory of "Quality Evaluation Through Morphological Identification", the correlation of both sides was studied systematically. Firstly, the thickness of PCC slices was measured by vernier calipers for classification, and the colour of PCC slice was estimated by naked eyes and automatic colorimeter and classified. Secondly, high performance liquid chromatography (HPLC) was used to establish fingerprint chromatogram containing 12 characteristic peaks, and the contents of moisture and ethanolic extractive were determined as well. The correlation among the appearance traits of PCC slice (including the thickness and the spatial values of colour of PCC slice powder: L*Lightness, a*Red-Green, b*Yellow-Blue) and peak areas of 12 characteristic peaks, contents of moisture and extractive were explored through multivariate statistical analysis tools, including Pearson's correlation analysis, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (PLS-DA) and analysis of variance (ANOVA). Association analysis results showed the morphological parameters (thickness and color) are significantly correlated with 2 kinds of principle chemical constituents (alkaloids and phenolic acids), among them, 5 major constituents including 2 isoquinoline alkaloids and 3 feruloylquinic acids were simultaneously quantitatively analyzed under the same chromatographic condition for establishing a correspondence between appearance traits and content of internal substances, and the sum of the contents of the five components was significantly higher in the thickness ≥ 4 mm (13.15% ± 2.25%) and bright yellow samples (12.14% ± 2.00%) than that in the thickness < 4 mm (10.89% ± 1.41%) and dark yellow samples (10.32% ± 2.41%). The research results confirm that thickness and colour, two main appearance parameters of PCC slice, can be used as the indicators for evaluating the quality PCC slice, which to some extent interprets the scientific connotation of traditional evaluation theory of "thick and yellow are better". At the same time, the results provided substantial data and foundation for the establishment of commodity grade standards of PCC slice.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

BACKGROUND: The Clinic for the Therapy Services (CTS) has considered reverting to face-to-face service delivery due to the downward trend in COVID-19 cases in the Philippines. However, the clinic has yet to investigate the willingness of the clients to this mode as a basis for its effective implementation. OBJECTIVES: The study described the readiness of CTS clients in returning to face-to-face therapy amidst the pandemic. It also discussed the factors affecting readiness based on a survey. METHODOLOGY: Fifty-five screened survey responses on the readiness of clients in returning to face-to-face therapy were gathered from January 30 to February 28, 2021. These underwent retrospective data analysis. Eight prospective online key informant interviews were conducted for clarifications in May 2022. This study utilized a descriptive analysis of quantitative categorical variables and a thematic content analysis of qualitative data. RESULTS: The majority of the respondents (35) stated readiness to attend face-to-face therapy followed by those who answered “No” (11), “Maybe” (5), and others (4). Factors that may have affected readiness included travel, characteristics of face-to-face therapy, health conditions, vaccine, and COVID-19 concerns. Frequently preferred health and safety strategies were the provision of hygiene products, disinfection, limited people inside the clinic, separate therapy areas, and ventilation. CONCLUSION Most of the respondents expressed willingness to receive face-to-face therapy in April or May of 2021. Feasibility of travel and decreased number of COVID-19 cases may have encouraged willingness to attend. Those who were hesitant reported concerns with traveling, characteristics of face-to-face therapy, health conditions, the COVID-19 situation, and the vaccine.
rehabilitation ; COVID-19

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].