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Abstract Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown. Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for the biosynthesis of JHB3 and JH III in D. melanogaster. The Cyp6g2 is predominantly expressed in the corpus allatum (CA), concurring with the expression pattern of jhamt, another well-studied gene that is crucial in the last steps of JH biosynthesis. Mutation in Cyp6g2 leads to severe disruptions in larval-pupal metamorphosis and exhibits reproductive deficiencies, exceeding those seen in jhamt mutants. Notably, Cyp6g2 −/− ::jhamt 2 double mutants all died at the pupal stage but could be rescued through the topical application of JH analogs. JH titer analyses revealed that both Cyp6g2 −/− mutant and jhamt 2 mutant lacking JHB3 and JH III, while overexpression of Cyp6g2 or jhamt caused a significant increase in JHB3 and JH III titer. Conclusions These findings collectively established that Cyp6g2 as the major JH epoxidase in the higher dipterans and laid the groundwork for the further understanding of JH biosynthesis. Moreover, these findings pave the way for developing specific Cyp6g2 inhibitors as insect growth regulators or insecticides.

Abstract The past decade has witnessed the significant efforts in novel material discovery in the use of data-driven techniques, in particular, machine learning (ML). However, since it needs to consider the precursors, experimental conditions, and availability of reactants, material synthesis is generally much more complex than property and structure prediction, and very few computational predictions are experimentally realized. To solve these challenges, a universal framework that integrates high-throughput experiments, a priori knowledge of chemistry, and ML techniques such as subgroup discovery and support vector machine is proposed to guide the experimental synthesis of materials, which is capable of disclosing structure-property relationship hidden in high-throughput experiments and rapidly screening out materials with high synthesis feasibility from vast chemical space. Through application of our approach to challenging and consequential synthesis problem of 2D silver/bismuth organic-inorganic hybrid perovskites, we have increased the success rate of the synthesis feasibility by a factor of four relative to traditional approaches. This study provides a practical route for solving multidimensional chemical acceleration problems with small dataset from typical laboratory with limited experimental resources available.

IntroductionHimalayan griffons (Gyps himalayensis), known as the scavenger of nature, are large scavenging raptors widely distributed on the Qinghai-Tibetan Plateau and play an important role in maintaining the balance of the plateau ecosystem. The gut microbiome is essential for host health, helping to maintain homeostasis, improving digestive efficiency, and promoting the development of the immune system. Changes in environment and diet can affect the composition and function of gut microbiota, ultimately impacting the host health and adaptation. Captive rearing is considered to be a way to protect Himalayan griffons and increase their population size. However, the effects of captivity on the structure and function of the gut microbial communities of Himalayan griffons are poorly understood. Still, availability of sequenced metagenomes and functional information for most griffons gut microbes remains limited.MethodsIn this study, metagenome sequencing was used to analyze the composition and functional structures of the gut microbiota of Himalayan griffons under wild and captive conditions.ResultsOur results showed no significant differences in the alpha diversity between the two groups, but significant differences in beta diversity. Taxonomic classification revealed that the most abundant phyla in the gut of Himalayan griffons were Fusobacteriota, Proteobacteria, Firmicutes_A, Bacteroidota, Firmicutes, Actinobacteriota, and Campylobacterota. At the functional level, a series of Kyoto Encyclopedia of Genes and Genome (KEGG) functional pathways, carbohydrate-active enzymes (CAZymes) categories, virulence factor genes (VFGs), and pathogen-host interactions (PHI) were annotated and compared between the two groups. In addition, we recovered nearly 130 metagenome-assembled genomes (MAGs).DiscussionIn summary, the present study provided a first inventory of the microbial genes and metagenome-assembled genomes related to the Himalayan griffons, marking a crucial first step toward a wider investigation of the scavengers microbiomes with the ultimate goal to contribute to the conservation and management strategies for this near threatened bird.

Objective: To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine (TCM) based on the regulation of gene expression. Methods: Genome-wide gene expression profiles of Michigan Cancer Foundation-7 (MCF-7) cells treated with or without 4 cholic acid derivatives were detected by gene chip technology. Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map (CMap) database. The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking. The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database, and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Results: Compared with the reference genome in the CMap database, the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic, anticancer, anti-inflammatory, and anti-infective drugs. Among them, 4 derivatives were associated with antianxiety drugs, and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gamma-aminobutyric acid (GABA) receptors. Moreover, the cytoskeletal pathway is one of the pathways enriched in the derivatives. Of them, ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells. Conclusion: The gene expression detection method, combined with CMap and pathway enrichment analysis, could be used to study the mechanism of the active ingredients of TCM. In addition, our research showed that cholic acid derivatives have a potential affinity for membrane receptors, where they can exert anxiolytic activity by modulating opioid receptor, GABA receptor, and dopamine receptor. Moreover, ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation, probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

Phosphodiesterase type 5 (PDE5), a cyclic nucleotide phosphodiesterase, controls the duration of the cyclic guanosine monophosphate (cGMP) signal by hydrolyzing cGMP to GMP. Inhibiting the activity of PDE5A has proven to be an effective strategy for treating pulmonary arterial hypertension and erectile dysfunction. Current enzymatic activity assay methods for PDE5A mainly use fluorescent or isotope-labeled substrates, which are expensive and inconvenient. Here, we developed an LC/MS-based enzymatic activity assay for PDE5A without labeling, which detects the enzymatic activity of PDE5A by quantifying the substrate cGMP and product GMP at a concentration of 100 nM. The accuracy of this method was verified by a fluorescently labeled substrate. Moreover, a new inhibitor of PDE5A was identified by this method and virtual screening. It inhibited PDE5A with an IC50 value of 870 nM. Overall, the proposed strategy provides a new method for screening PDE5A inhibitors.

Abstract The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.

Rehmanniae Radix Preparata (RRP) has been used to management of osteoporotic pain in traditional Chinese medicine trials. However, how RRP exhibits the anti-nociceptive effect remains largely unknown. To this end, estrogen-deficient rats were orally gavaged with aqueous RRP extracts for 12 weeks. The tail flick latency, Von-Frey and formalin assays were employed to evaluate pain sensitization. The administration of RRP alleviates allodynia and hyperalgesia in estrogen-deficient rats. These alterations were associated with a decrease in the expression of substance P (SP), neurokinin-1 receptor (NK-1R), phospho (p)-PI3K, p-protein kinase B (Akt), and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the spinal cord. In addition, RRP improves bone quality in the rats. These results suggest RRP could attenuate pain sensitization and improve bone quality through regulation of PI3K/Akt/TRPV1 signaling pathway during menopause stages. And RRP is considered a novel source of anti-osteoporotic pain drug candidates.

Ecdysteroids are crucial in regulating the growth and development of insects. In the fruit fly Drosophila melanogaster, both C27 and C28 ecdysteroids have been identified. While the biosynthetic pathway of the C27 ecdysteroid 20-hydroxyecdysone (20E) from cholesterol is relatively well understood, the biosynthetic pathway of C28 ecdysteroids from C28 or C29 dietary sterols remains unknown. In this study, we found that different dietary sterols (including the C27 sterols cholesterol and 7-dehydrocholesterol, the C28 sterols brassicasterol, campesterol, and ergosterol, and the C29 sterols β-sitosterol, α-spinasterol, and stigmasterol) differentially affected the expression of 20E biosynthetic genes to varying degrees, but similarly activated 20E primary response gene expression in D. melanogaster Kc cells. We also found that a single dietary sterol was sufficient to support D. melanogaster growth and development. Furthermore, the expression levels of some 20E biosynthetic genes were significantly altered, whereas the expression of 20E signaling primary response genes remained unaffected when flies were reared on lipid-depleted diets supplemented with single sterol types. Overall, our study provided preliminary clues to suggest that the same enzymatic system responsible for the classical C27 ecdysteroid 20E biosynthetic pathway also participated in the conversion of C28 and C29 dietary sterols into C28 ecdysteroids.

Abstract Background Shikonin, a natural naphthoquinone, is abundant in Chinese herb medicine Zicao (purple gromwell) and has a wide range of biological activities, especially for cancer. Shikonin and its analogues have been reported to induce cell-cycle arrest, but target information is still unclear. We hypothesized that shikonin, with a structure similar to that of quinone-type compounds, which are inhibitors of cell division cycle 25 (Cdc25) phosphatases, will have similar effects on Cdc25s. To test this hypothesis, the effects of shikonin on Cdc25s and cell-cycle progression were determined in this paper. Methods The in vitro effects of shikonin and its analogues on Cdc25s were detected by fluorometric assay kit. The binding mode between shikonin and Cdc25B was modelled by molecular docking. The dephosphorylating level of cyclin-dependent kinase 1 (CDK1), a natural substrate of Cdc25B, was tested by Western blotting. The effect of shikonin on cell cycle progression was investigated by flow cytometry analysis. We also tested the anti-proliferation activity of shikonin on cancer cell lines by MTT assay. Moreover, in vivo anti-proliferation activity was tested in a mouse xenograft tumour model. Results Shikonin and its analogues inhibited recombinant human Cdc25 A, B, and C phosphatase with IC50 values ranging from 2.14 ± 0.21 to 13.45 ± 1.45 μM irreversibly. The molecular modelling results showed that shikonin bound to the inhibitor binding pocket of Cdc25B with a favourable binding mode through hydrophobic interactions and hydrogen bonds. In addition, an accumulation of the tyrosine 15-phosphorylated form of CDK1 was induced by shikonin in a concentration-dependent manner in vitro and in vivo. We also confirmed that shikonin showed an anti-proliferation effect on three cancer cell lines with IC50 values ranging from 6.15 ± 0.46 to 9.56 ± 1.03 μM. Furthermore, shikonin showed a promising anti-proliferation effect on a K562 mouse xenograph tumour model. Conclusion In this study, we provide evidence for how shikonin induces cell cycle arrest and functions as a Cdc25s inhibitor. It shows an anti-proliferation effect both in vitro and in vivo by mediating Cdc25s.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro. Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.

The American cockroach (Periplaneta americana) is an hemimetabolous insect with rapid growth, high fecundity, and remarkable tissue-regeneration capability. Here Li et al sequence its 3.38-Gb genome and perform the functional studies, yielding insights into its environmental adaptation and developmental plasticity.

Cysteine 473, within the active site of the enzyme, Cdc25B, is catalytically essential for substrate activation. The most well-reported inhibitors of Cdc25 phosphatases, especially quinone-type inhibitors, function by inducing irreversible oxidation at this active site of cysteine. Here, we identified a natural product, HB-21, having a sesquiterpene lactone skeleton that could irreversibly bind to cys473 through the formation of a covalent bond. This compound inhibited recombinant human Cdc25B phosphatase with an IC50 value of 24.25 μM. Molecular modeling predicted that HB-21 not only covalently binds to cys473 of Cdc25B but also forms six hydrogen bonds with residues at the active site. Moreover, HB-21 can dephosphorylate cyclin-dependent kinase (CDK1), the natural substrate of Cdc25b, and inhibit cell cycle progression. In summary, HB-21 is a new type of Cdc25B inhibitor with a novel molecular mechanism.

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis.

[This corrects the article DOI: 10.1371/journal.pgen.1005038.].

The geometrical, electronic structure, and magnetic properties of the half-metallocene of M (M = Fe, Co, Ni) adsorbed on Stone–Wales defected graphene (SWG) were studied using the density functional theory (DFT), aiming to tune the band structure of SWG. The introduction of cyclopentadienyl (Cp) and half-metallocene strongly affected the band structure of SWG. The magnetic properties of the complex systems originated from the 3D orbitals of M (M = Fe, Co, Ni), the molecular orbital of Cp, and SWG. This phenomenon was different from that found in a previous study, which was due to metal ion-induced sandwich complexes. The results have potential applications in the design of electronic devices based on SWG.

The electronic and optical properties of the rare earth metal atom-doped anatase TiO2 have been investigated systematically via density functional theory calculations. The results show that TiO2 doped by Ce or Pr is the optimal choice because of its small band gap and strong optical absorption. Rare earth metal atom doping induces several impurity states that tune the location of valence and conduction bands and an obvious lattice distortion that should reduce the probability of electron–hole recombination. This effect of band change originates from the 4f electrons of the rare earth metal atoms, which leads to an improved visible light absorption. This finding indicates that the electronic structure of anatase TiO2 is tuned by the introduction of impurity atoms.

Corpus allatum (CA) ablation results in juvenile hormone (JH) deficiency and pupal lethality in Drosophila. The fly CA produces and releases three sesquiterpenoid hormones: JH III bisepoxide (JHB3), JH III, and methyl farnesoate (MF). In the whole body extracts, MF is the most abundant sesquiterpenoid, followed by JHB3 and JH III. Knockout of JH acid methyl transferase (jhamt) did not result in lethality; it decreased biosynthesis of JHB3, but MF biosynthesis was not affected. RNAi-mediated reduction of 3-hydroxy-3-methylglutaryl CoA reductase (hmgcr) expression in the CA decreased biosynthesis and titers of the three sesquiterpenoids, resulting in partial lethality. Reducing hmgcr expression in the CA of the jhamt mutant further decreased MF titer to a very low level, and caused complete lethality. JH III, JHB3, and MF function through Met and Gce, the two JH receptors, and induce expression of Kr-h1, a JH primary-response gene. As well, a portion of MF is converted to JHB3 in the hemolymph or peripheral tissues. Topical application of JHB3, JH III, or MF precluded lethality in JH-deficient animals, but not in the Met gce double mutant. Taken together, these experiments show that MF is produced by the larval CA and released into the hemolymph, from where it exerts its anti-metamorphic effects indirectly after conversion to JHB3, as well as acting as a hormone itself through the two JH receptors, Met and Gce.

Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)2D3/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

In Lepidoptera and Diptera, the fat body dissociates into single cells in nondiapause pupae, but it does not dissociate in diapause pupae until diapause termination. Using the cotton bollworm, Helicoverpa armigera, as a model of pupal diapause insects, we illustrated the catalytic mechanism and physiological importance of fat body cell dissociation in regulating pupal development and diapause. In nondiapause pupae, cathepsin L (CatL) activates matrix metalloproteinases (Mmps) that degrade extracellular matrix proteins and cause fat body cell dissociation. Mmp-induced fat body cell dissociation activates lipid metabolism through transcriptional regulation, and the resulting energetic supplies increase brain metabolic activity (i.e., mitochondria respiration and insulin signaling) and thus promote pupal development. In diapause pupae, low activities of CatL and Mmps prevent fat body cell dissociation and lipid metabolism from occurring, maintaining pupal diapause. Importantly, as demonstrated by chemical inhibitor treatments and CRISPR-mediated gene knockouts, Mmp inhibition delayed pupal development and moderately increased the incidence of pupal diapause, while Mmp stimulation promoted pupal development and moderately averted pupal diapause. This study advances our recent understanding of fat body biology and insect diapause regulation. [ABSTRACT FROM AUTHOR]

In order to master the mechanical strength characteristics of the colluvial deposit and the influence of water content on it，a typical loose colluvial deposit of landslide in southwest China was taken as a research object. A series of large-scale direct shear tests were carried out under different water content conditions and normal stress, the macro mechanical characteristics such as stress-strain, particle breakage, volumetric strain, shear plane failure and so on in the shear process of the colluvial deposit were analyzed, and the determination method suitable for its shear strength was proposed. The research indicates that the colluvial deposit shows obvious strain hardening characteristics under different water contents, and the shear stress displacement curve has no significant peak value, but there is a certain degree of stress "jump" phenomenon. Besides, the shear process produces a relatively obvious particle crushing phenomenon, and the relative particle crushing rate increases with the decrease of water content or the increase of normal stress. Meanwhile, the tests show that the shape of shear failure surface is not an ideal plane. With the increase of water content, the shear surface gradually changes from an irregular shape of "convex up and concave down" to a flat failure surface with a certain angle with the shear joint in space. Combined with the analysis of the characteristics of the normal stress, shear stress and stress ratio on the shear plane during the shear process, a method for determining the shear strength of the accumulation based on the stress ratio is proposed, and the effectiveness of this method is verified. This method is not only simple to operate, with little human interference, but also can better reflect the essence of the shear failure of the soil rock mixture. Finally, the tests reveal that water has an obvious softening effect on the colluvial deposit. The apparent cohesion c and internal friction angle φ linearly decrease approximately with the increase of water content, and the deterioration effect of apparent cohesion is greater than that of internal friction angle. The research results can provide a reference for the determination of shear mechanical properties and strength values of deposits in the southwest mountain area.