Ti3C2 nanosheet-induced autophagy derails ovarian functions.

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. RESULTS: We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. CONCLUSION: Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.

Light-Intensity Switching of Graphene/WSe2 Synaptic Devices.

2D van der Waals heterojunctions (vdWH) have emerged as an attractive platform for the realization of optoelectronic synaptic devices, which are critical for energy-efficient computing systems. Photogating induced by charge traps at the interfaces indeed results in ultrahigh responsivity and tunable photoconductance. Yet, optical potentiation and depression remain mostly modulated by gate bias, requiring relatively high energy inputs. Thus, advanced all-optical synapse switching strategies are still needed. In this work, a reversible switching between positive photoconductivity (PPC) and negative photoconductivity (NPC) is achieved in graphene/WSe2 vdWH solely through light-intensity modulation. Consequently, the graphene/WSe2 synaptic device shows tunable optical potentiation and depression behavior with an ultralow power consumption of 127 aJ. The study further unravels the complex interplay of gate bias and incident light power in determining the sign and magnitude of the photocurrent, showing the critical role of charge trapping and photogating at interfaces. Interestingly, it is found that switching between PPC to NPC can be also obtained at 0 mV drain-source voltage. Overall, the reversible potentiation/depression effect based on light intensity modulation and its combination with additional gate bias tunability is very appealing for the development of energy-efficient optical communications and neuromorphic computing.

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Toward Broadband Photodetection: Band Alignment and Interlayer Charge Transfer in 2D Transition Metal Dichalcogenides/3D-Ga2O3 Hybrid-Dimensional Heterostructures.

Recently, various transition metal dichalcogenides (TMDs)/Ga2O3 heterostructures have emerged as excellent candidates for the development of broadband photodetection, exhibiting various merits such as broadband optical absorption, efficient interlayer carrier transfer, a relatively simple fabrication process, and potential for flexibility. In this work, vertically stacked MoSe2/Ga2O3, WS2/Ga2O3, and WSe2/Ga2O3 heterostructures were experimentally synthesized, all exhibiting broadband light absorption, spanning at least from 200 to 800 nm. The absorption coefficients of these TMDs/Ga2O3 heterostructures are significantly improved compared to those of individual Ga2O3 films. The superior performance can be attributed to the type-I band alignment and efficient interlayer carrier transfer, which result from various band offsets along with the different doping conditions of the TMD layers, leading to distinct photoluminescence (PL) emission properties. Through a detailed analysis of the excitation-power-dependent PL spectra, we offer an in-depth discussion of the interlayer carrier transfer mechanism in the TMDs/Ga2O3 heterostructures. Regarding interlayer coupling effects, the shift of the EF of TMD layers plays a crucial role in modulating their trion emission properties. These findings suggest that these three TMDs/Ga2O3 heterostructures have great potential in broadband photodetection, and our in-depth physical mechanism analysis lays a solid foundation for a new device design.

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy.

Accurate prediction of the relative biological effectiveness (RBE) of boron neutron capture therapy (BNCT) is challenging. The therapy is different from other radiotherapy; the dynamic distribution of boron-containing compounds in tumor cells affects the therapeutic outcome considerably and hampers accurate measurement of the neutron-absorbed dose. Herein, we used boron-containing metal-organic framework nanoparticles (BMOFs) with high boron content to target U87-MG cells and maintain the concentration of the 10B isotope in cells. The content of boron in the cells could maintain 90% (60 ppm) within 20 min compared with that at the beginning; therefore, the accurate RBE of BNCT can be acquired. The effects of BNCT upon cells after neutron irradiation were observed, and the neutron-absorbed dose was obtained by Monte Carlo simulations. The RBE of BMOFs was 6.78, which was 4.1-fold higher than that of a small-molecule boron-containing agent (boric acid). The energy spectrum of various particles was analyzed by Monte Carlo simulations, and the RBE was verified theoretically. Our results suggested that the use of nanoparticle-based boron carriers in BNCT may have many advantages and that maintaining a stable boron distribution within cells may significantly improve the efficiency of BNCT.

Palladium-Catalyzed Synthesis of Indanone via C-H Annulation Reaction of Aldehydes with Norbornenes.

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

Sea Cucumber Peptides Ameliorate DSS-Induced Ulcerative Colitis: The Role of the Gut Microbiota, the Intestinal Barrier, and Macrophage Polarization.

The incidence of ulcerative colitis (UC) is increasing annually. There are few treatments for UC patients, and some drugs have serious side effects. Sea cucumber peptide (SCP) has anti-inflammatory, antioxidant and other biological activities, and various sea cucumber species are in pharmaceutical development. However, relevant studies on the effects of SCP on UC progression are still lacking. In this study, a mouse model of acute colitis was induced by 3% dextran sulfate (DSS), and the effect of 500 mg/kg SCP on colitis was investigated. The results showed that SCP can alleviate DSS-induced colon damage and intestinal barrier damage. SCP significantly inhibited the expression of inflammatory factors and oxidative stress in UC mice. SCP reversed the intestinal microbiota dysregulation induced by DSS, inhibited the growth of Sutterella, Prevotella_9 and Escherichia-Shigella harmful bacteria, and increased the abundance of Lachnospiraceae_NK4A136_group. At the same time, SCP treatment significantly inhibited the LPS-induced polarization of M1 macrophages, which may be mediated by two monopeptides, IPGAPGVP and TGPIGPPGSP, via FPR2. In conclusion, SCP can protect against colitis by modulating the intestinal microbiota composition and the intestinal barrier and inhibiting the polarization of M1 macrophages.

Integrating network pharmacology and experimental verification strategies to reveal the active ingredients and molecular mechanism of Tenghuang Jiangu Capsule against osteoporosis.

Tenghuang Jiangu Capsule (THJGC) is a Chinese herbal formula used for the treatment of osteoporosis and osteoarthritis in China, but its mechanism for treating osteoporosis is not clear. The aim of this study was to investigate the therapeutic effect of THJGC on osteoporosis and its intrinsic mechanism through network pharmacology and experimental validation. Drugs and potential targets were obtained from several reliable databases through network pharmacology, and these targets were integrated and analyzed using bioinformatics and molecular docking strategies. Quercetin, lignans and kaempferol were identified as key components, and the key targets included Akt1, MAPKs, and CASP3. Subsequently, UPLC-MS/MS analysis confirmed the presence of components in THJGC for the treatment of osteoporosis. In addition, using ex vivo and in vivo models, it was confirmed that THJGC inhibited H2O2-induced ROS generation and apoptosis, and reduced OVX-induced bone loss in a mouse model of osteoporosis. Our data suggest that THJGC has antioxidant, bone formation-promoting, bone resorption-inhibiting, and MC3T3-E1 apoptosis-reducing effects, and thus has anti-osteoporotic properties. In conclusion, it may be a promising pharmacologic adjuvant treatment for osteoporosis.

A fuzzy mathematical model for hybrid inventory and purchase optimization in a reverse logistics system considering shortage and warehouse capacity.

Making decisions about the design and implementation of a logistics network is crucial as it has long-term impacts. However, it is important to consider that demand factors and the number of returned items by customers may change over time. Therefore, it is necessary to design a logistics network that can adapt to various demand fluctuations. The main goal of this study is to calculate the quantity of products that should be sent at different times in a supply chain network to minimize the overall cost of reverse logistics and tardiness time. Accordingly, a multi-objective mathematical model is proposed that aims to optimize the total cost and the amount of delay in sending customer orders in a three-level logistics network, assuming that some parameters are uncertain. Additionally, the minimization of waiting time, considering the level of delay in sending, is applied as the second objective function. To handle the uncertainty in the reverse logistics network, a fuzzy approach is implemented, and the proposed model is solved using GAMS software. Furthermore, to solve the mathematical model in large dimensions, the Cuckoo Optimization Algorithm (COA) is applied in MATLAB software, and the results are compared to the global optimal solution. The outcomes show that the proposed algorithm has a desirable performance, as the total values sent to the manufacturer are equal to those obtained from the exact solution, and the objective function value decreases as the number of repetitions increases.

Palladium-Catalyzed Direct Esterification via C-H Bond Activation of Aldehydes.

A concise and highly efficient synthesis method of direct esterification of aldehydes via Pd-catalyzed C-H bond activation of aldehyde group has been developed. The strategy avoids the preoxidation step of aldehyde or use of condensing agents in ester synthesis, which is not only applicable to various alcohols but also suitable for the esterification of phenolics which are usually difficult to be esterified. The methodology has the significant advantages of broad substrate scope, mild reaction conditions, and nonrequirement of additional oxidants.

Bile salt hydrolase of Lactiplantibacillus plantarum plays important roles in amelioration of DSS-induced colitis.

Bile salt hydrolases are thought to be the gatekeepers of bile acid metabolism. To study the role of BSH in colitis, we investigated the ameliorative effects of different BSH-knockout strains of Lactiplantibacillus plantarum AR113. The results showed that L. plantarum Δbsh 1 and Δbsh 3 treatments did not improve body weight and alleviate the hyperactivated myeloperoxidase activity to the DSS group. However, the findings for L. plantarum AR113, L. plantarum Δbsh 2 and Δbsh 4 treatments were completely opposite. The double and triple bsh knockout strains further confirmed that BSH 1 and BSH 3 are critical for the ameliorative effects of L. plantarum AR113. In addition, L. plantarum Δbsh 1 and Δbsh 3 did not significantly inhibit the increase in pro-inflammatory cytokines or the decrease in an anti-inflammatory cytokine. These results suggest that BSH 1 and BSH 3 in L. plantarum play important roles in alleviating enteritis symptoms.

Fermentation Quality, In Vitro Digestibility, and Aerobic Stability of Ensiling Spent Mushroom Substrate with Microbial Additives.

This experiment investigated the effects of lactic acid bacteria and cellulase on the fermentation quality, in vitro digestibility, and aerobic stability of Flammulina velutipes spent mushroom substrate silage (F-silage) and Pleurotus eryngii spent mushroom substrate silage (P-silage). Silage treatments included groups without any additives (control), with lactic acid bacteria (L), with cellulase (E), and with lactic acid bacteria and cellulase (M). Data analysis was performed using independent sample t-test and analysis of variance. After 45 days of ensiling, the pH in F-silage and P-silage from the L, E, and M groups were lower than those in the control group (p < 0.05). The pH, acetic acid (AA), and propionic acid (PA) levels in P-silage were lower than those in F-silage, and the LA content in P-silage was higher than that in F-silage (p < 0.05). Compared with the control, the E treatment increased in vitro neutral detergent fibre digestibility (IVNDFD) and in vitro acid detergent fibre digestibility (IVADFD) in F-silage and P-silage (p < 0.05). The aerobic stability of F-silage inoculated with L increased (p < 0.05) by 24 h compared to the control. The aerobic stability of P-silage inoculated with M increased (p < 0.05) by 6 h compared to the control. The improvement in fermentation quality and aerobic stability is extremely large in terms of applying M in F-silage and P-silage. The E is effective in improving the in vitro digestibility of P-silage. The research results provide a theoretical basis for the production of high-quality spent mushroom substrate fermented feed.

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments.

Background: This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1ß) inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods: In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1ß in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1ß. Result: 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1ß mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1ß inhibitor. Conclusion: Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1ß inhibitors development in GA.

Simulation and Projection of Climate Extremes in China by a Set of Statistical Downscaled Data.

This study assesses present-day extreme climate changes over China by using a set of phase 6 of the Coupled Model Intercomparison Project (CMIP6) statistical downscaled data and raw models outputs. The downscaled data is produced by the adapted spatial disaggregation and equal distance cumulative distribution function (EDCDF) method at the resolution of 0.25° × 0.25° for the present day (1961-2014) and the future period (2015-2100) under the Shared Socioeconomic Path-way (SSP) 2-4.5 than SSP5-8.5 emission scenario. The results show that the downscaling method improves the spatial distributions of extreme climate events in China with higher spatial pattern correlations, Taylor Skill Scores and closer magnitudes no matter single model or multi model ensemble (MME). In the future projections, large inter-model variability between the downscaled models still exists, particular for maximum consecutive 5-day precipitation (RX5). The downscaled MME projects that total precipitation (PTOT) and RX5, will increase with time, especially for the northwest China. The projected heavy precipitation days (R20) also increase in the future. The region of significant increase in R20 locates in the south of river Yangtze. Maxi-mum annual temperature (TXX) and percentage of warm days (TX90p) are projected to increase across the whole country with larger magnitude over the west China. Projected changes of minimum annual temperature (TNN) over the northeastern China is the most significant area. The higher of the emission scenario, the more significant of extreme climates. This reveals that the spatial distribution of extreme climate events will become more uneven in the future.

Soft Sensor Modeling Method Based on Improved KH-RBF Neural Network Bacteria Concentration in Marine Alkaline Protease Fermentation Process.

Marine alkaline protease (MAP) fermentation is a complex multivariable, multi-coupled, and nonlinear process. Some unmeasured parameters will affect the quality of protease. Aiming at the problem that some parameters are difficult to be detected online, a soft sensing modeling method based on improved Krill Herd algorithm RBF neural network (LKH-RBFNN) is proposed in this paper. Based on the multi-parameter RBFNN model, the adaptive RBF neural network algorithm and control law are used to approximate the unknown parameters. The adaptive Levy flight strategy is used to improve the traditional Krill Herd algorithm, improve the global search ability of the algorithm, and avoid falling into local optimization. At the same time, the location update formula of Krill Herd algorithm is improved by using the calculation methods of similarity and agglomeration degree, and the parameters of adaptive RBFNN are optimized to improve its over correction and large amount of calculation. Finally, the soft sensing prediction model of bacterial concentration and relative active enzyme in map process based on LKH-RBFNN is established. The root mean square error and maximum absolute error of this model are 0.938 and 0.569, respectively, which are less than KH-RBFNN and PSO-RBFNN prediction models. It proves that the prediction error of LKH-RBFNN model is smaller and can meet the needs of online prediction of key parameters of map fermentation.

The disruption of human trophoblast functions by autophagy activation through PI3K/AKT/mTOR pathway induced by exposure to titanium carbide (Ti3C2) MXene.

Ti3C2 MXene, as a novel nanomaterial, has attracted great attention due to its promising properties in biomedical applications. However, the potential effects of Ti3C2 MXene on trophoblast functions have not been investigated. Here, we found that Ti3C2 MXene exposure weakened the extension ability of villus explants in vitro. We employed human trophoblast HTR-8/SVneo cells to reveal the underlying molecular mechanisms by which Ti3C2 MXene exposure affected trophoblast functions. Results showed that Ti3C2 MXene entered cells and mostly deposited in the cytoplasm, inhibiting cell migration and invasion abilities. Furthermore, we found that Ti3C2 MXene exposure elevated autophagy through the inhibition of the PI3K/AKT/mTOR pathway. Meanwhile, the application of an autophagy inhibitor (3-MA) prevented autophagy and restored cell viability, resulting in the recovery of cell migration and invasion abilities. These indicated that the cellular dysfunction induced by Ti3C2 MXene may be mediated by autophagy activation. Our results indicated that autophagy is a key factor in eliciting HTR-8/SVneo dysfunction after Ti3C2 MXene exposure, which could therefore damage placental development. Autophagy inhibition is a potential therapeutic strategy for alleviating the placental toxicity of nanoparticles.

Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice.

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of Ti3C2 on human health remain poorly understood. RESULTS: To explore the influence on foetal or offspring after exposure to Ti3C2 nanosheets, we established a mouse model exposed to different doses of Ti3C2 nanosheets during early pregnancy in this study. We found that Ti3C2 nanosheets had negligible effect on the reproductive ability of maternal mice, including average pregnancy days, number of new-borns, and neonatal weight, etc. Unexpectedly, abnormal neurobehavior and pathological changes in the cerebral hippocampus and cortex in adult offspring were observed following Ti3C2 nanosheet treatment. In further studies, it was found that Ti3C2 exposure led to developmental and functional defects in the placenta, including reduced area of labyrinth, disordered secretion of placental hormones, and metabolic function derailment. The long-chain unsaturated fatty acids were significantly higher in the placenta after Ti3C2 exposure, especially docosahexaenoic acid (DHA) and linoleic acid. The metabolic pathway analysis showed that biosynthesis of unsaturated fatty acids was upregulated while linoleic acid metabolism was downregulated. CONCLUSIONS: These developmental and functional defects, particularly metabolic function derailment in placenta may be the cause for the neuropathology in the offspring. This is the first report about the effects of Ti3C2 nanosheet exposure on pregnancy and offspring. The data provides a better understanding of Ti3C2 nanosheets safety. It is suggested that future studies should pay more attention to the long-term effects of nanomaterials exposure, including the health of offspring in adulthood, rather than only focus on short-term effects, such as pregnancy outcomes. Metabolomics could provide clues for finding the prevention targets of the biological negative effect of Ti3C2 nanosheets.

Genes encoding bile salt hydrolase differentially affect adhesion of Lactiplantibacillus plantarum AR113.

BACKGROUND: Adhesion is considered important for Lactiplantibacillus to persist in the human gut and for it to exert probiotic effects. Lactiplantibacillus plantarum contains a considerable number and variety of genes encoding bile salt hydrolases (bsh), but their effects on microbial adhesion remain poorly understood. To clarify the effects of four bsh on adhesion, we tried to knock out bsh (Δbsh) of L. plantarum AR113 using the CRISPR-Cas9 method, and compared the growth, auto-aggregation (RAA ), co-aggregation (RCA ), surface hydrophobicity (AHC ) of AR113 wild-type and Δbsh strains and their adhesion abilities to HT29 cells. RESULTS: We first obtained the AR113 Δbsh1,3,2,4 strain with four bsh knocked out. Their growth was significantly slower than the wild-type strain cultured in De Man, Rogosa, and Sharpe medium (MRS) with 3.0 g L-1 glyco- or tauro-conjugated bile acid. Bsh had no significant effect on the growth of ten strains cultured in MRS, but Δbsh1 inhibited their growth when cultured in MRS containing 3.0 g L-1 sodium glycocholate, whereas Δbsh4 instead promoted their growth in MRS with 3.0 g L-1 sodium glycocholate and sodium taurocholate. RCA and RAA were linearly positive for all strains except AR113 Δbsh2,4, and AHC and RAA were negatively correlated for most strains excluding AR113 Δbsh2, with RAA  = 6.38-25.05%, RCA  = 5.17-9.22%, and ACH  = 3.22-47.71%. The adhesion ability of ten strains cultured in MRS was higher than that of strains cultured in MRS with 3.0 g L-1 bovine bile, and it was related to bsh2. CONCLUSION: Bsh differentially affected the adhesion of AR113 series strains. This adds to the available information about substrate-gene-performance, and provides new information to enable engineering to regulate the colonization of Lactiplantibacillus. © 2021 Society of Chemical Industry.

A Network Pharmacology and Molecular Docking Strategy to Explore Potential Targets and Mechanisms Underlying the Effect of Curcumin on Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. METHODS: Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. RESULTS: 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. CONCLUSION: The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

Rictor/mTORC2 is involved in endometrial receptivity by regulating epithelial remodeling.

Successful embryo implantation requires well-functioning endometrial luminal epithelial cells to establish uterine receptivity. Inadequate uterine receptivity is responsible for approximately two thirds of implantation failures in humans. However, the regulatory mechanism governing this functional process remains largely unexplored. A previous study revealed that the expression of Rictor, the main member of mTORC2, in mouse epithelial cells is increased on the fourth day of gestation (D4). Here, we provide the first report of the involvement of Rictor in the regulation of endometrial receptivity. Rictor was conditionally ablated in the mouse endometrium using a progesterone receptor cre (PRcre ) mouse model. Loss of Rictor altered polarity remodeling and the Na+ channel protein of endometrial cells by mediating Rac-1/PAK1(pPAK1)/ERM(pERM) and Sgk1/pSgk1 signaling, respectively, ultimately resulting in impaired fertility. In the endometrium of women with infertility, the expression of Rictor was changed, along with the morphological transformation and Na+ channel protein of epithelial cells. Our findings demonstrate that Rictor is crucial for the establishment of uterine receptivity in both mice and humans. The present study may help improve the molecular regulatory network of endometrial receptivity and provide new diagnostic and treatment strategies for infertility.