Impaired meningeal lymphatic drainage in Listeria monocytogenes infection.

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

3D net-like Co3O4@NiO nanostructures for high performance supercapacitors.

Co3O4@NiO composite electrode materials were successfully synthesized by a two-step hydrothermal method followed by annealing treatment. Due to their three-dimensional network structure, these composite materials exhibited a large specific surface area, enhancing their electrochemical performance. Consequently, the Co3O4@NiO electrode demonstrated a specific capacitance of 1306 F g-1 at a current density of 1 A g-1, an excellent specific capacitance retention rate of 95.5% after 3000 cycles even at 8 A g-1 and a coulombic efficiency approaching 100%. These outstanding properties make the Co3O4@NiO composite materials promising electrode materials for high performance supercapacitors.

Identification and characterization of two O-methyltransferases involved in methylated 2-(2-phenethyl) chromones biosynthesis in agarwood.

The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-methyltransferases (OMTs) are necessary for the methylated PECs biosynthesis, however, there is little information known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PECs content revealed that the AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. The vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl) chromone. The transient overexpression experiment in Qi-Nan revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.

Microneedling Therapy for Striae Distensae: Systematic Review and Meta-Analysis.

INTRODUCTION: Striae distensae (SD), linear scars of derma, caused by disproportionate skin stretching, which indicates a cosmetic problem and even endangers individuals' psychosocial health. Microneedling, representing a relatively new procedural therapy, has shown brightening but diverse results in the remedy of SD. Our study systematically investigates and further evaluates the efficacy of microneedling for SD. METHOD: This study was conducted following the PRISMA guidelines. According to the preplanned search strategy, four electronic databases were comprehensively searched for eligible clinical controlled studies. Standardized mean difference (SMD) and odd ratio (OR) with 95% confidence intervals were calculated for continuous data and dichotomous data, respectively. RESULTS: According to the predetermined criteria, eleven eligible articles of six RCTs and five non-RCTs were included. Concerning clinical improvement, a significant difference was observed in the microneedle radiofrequency treatment subgroup (SMD: 0.57, 95% CI 0.20-0.94, P = 0.003). The pooled result of the second subgroup revealed that microneedling and lasers producing almost comparable effectiveness for treating SD with no significant difference (P = 0.35). The analysis result of the third subgroup of microneedling versus non-laser therapy indicated significant difference at the 5% significance level (SMD:1.01, 95% CI 0.51-1.51, P < 0.0001). With regard to patient satisfaction, the pooled estimate concluded that participants' satisfaction with therapeutic effect between MRF and laser group was comparable (P = 0.26), whereas microneedling exhibited significant superiority than both laser (P = 0.04) and non-laser treatments (SMD: 0.95, 95% CI 0.52-1.38, P < 0.0001). Occurrence of post-inflammatory hyperpigmentation (PIH) was not obvious in microneedling therapy compared to other treatments, and a statistically difference was observed (P = 0.0003). Microneedling treatment caused significant pain compared with laser therapy (P < 0.00001). CONCLUSION: This systematic review and meta-analysis has provided initial evidence of the efficacy and safety of microneedling technology for SD. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Focusing Micromechanical Polaritons in Topologically Nontrivial Hyperbolic Metasurfaces.

Vertically stacked multiple atomically thin layers have recently widened the landscape of rich optical structures thanks to these quantum metamaterials or van der Waals (vdW) materials, featuring hyperbolic polaritons with unprecedented avenues for light. Despite their far-reaching implications, most of their properties rest entirely on a trivial band topological origin. Here, a 2D approach is adopted toward a micromechanical vdW analogue that, as a result of engineered chiral and mirror symmetries, provides topologically resilient hyperbolic radiation of mechanical vibrations in the ultrasonic regime. By applying laser vibrometry of the micrometer-sized metasurface, we are able to exhibit the exotic fingerprints of robust hyperbolic radiation spanning several frequencies, which beyond their physical relevance, may enable ultrasonic technologies.

A multiple Arc (mArc) tagging system to uncover the organizational principles of multiple memories.

Engrams or memory traces are the neuronal ensembles that collectively store individual experiences. Genetic strategies based on immediate early genes (IEGs), such as Arc/Arg3.1 , allow us to tag the ensembles active during memory encoding and compare them to those active during retrieval. However, these strategies only allow for the tagging of one neural ensemble. Here, we developed a multiple Arc (mArc) system that allows for the tagging of two Arc + ensembles. We validated this system by investigating how context, time, and valence influence neuronal ensemble reactivation in the dentate gyrus (DG). We show that similar contextual and valenced experiences are encoded in overlapping DG ensembles. We also find that ensembles are modulated by time, where experiences closer in time are encoded in more similar ensembles. These results highlight the dynamic nature of DG ensembles and show that the mArc system provides a powerful approach for investigating multiple memories in the brain. HIGHLIGHTS: The mArc system allows for the tagging of two Arc + ensembles in the same mouse DG ensembles labeled by the mArc system receive increased excitatory inputContext, valence, and time influence DG ensemble reactivationDG neural ensembles are reactivated less with increasing time.

Mitigation of reverse osmosis membrane fouling by coagulation pretreatment to remove silica and transparent exopolymer particles.

The dissolution of silica and transparent exopolymer particles (TEP) can deposit on the membrane surface and cause serious membrane fouling in reverse osmosis (RO) technology. Coagulation, as a common pretreatment process for RO, can effectively intercept pollutants and alleviate membrane fouling. In this study, FeCl3 and AlCl3 coagulants and polyacrylamide (PAM) flocculants were used to explore the optimal coagulation conditions to reduce the concentration of silica and TEP in the RO process. The results showed that the two coagulants had the best removal effect on pollutants when the pH was 7 and the dosage was 50 mg/L. Considering the proportion of reversible fouling after coagulation, the removal rate of pollutants, and the residual amount of coagulation metal ions, the best PAM dosage was 5 mg/L for FeCl3 and 1 mg/L for AlCl3. After coagulation pretreatment, the Zeta potential decreased, and the particle size distribution increased, making pollutants tend to aggregate, thus effectively removing foulants. The removal mechanisms of pollutants by coagulation pretreatment were determined to be adsorption, electric neutralization and co-precipitation. This study determined the best removal conditions of silica and TEP by coagulation and explored the removal mechanism.

Nanowires Framework Supported Porous Lotus-Carbon Anode Boosts Lithium-Ion and Sodium-Ion Batteries.

The novel design of carbon materials with stable nanoarchitecture and optimized electrical properties featuring simultaneous intercalation of lithium ions (Li+ ) and sodium ions (Na+ ) is of great significance for the superb lithium- sodium storage capacities. Biomass-derived carbon materials with affluent porosity have been widely studied as anodes for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). However, it remains unexplored to further enhance the stability and utilization of the porous carbon skeleton during cycles. Here, a lotus stems derived porous carbon (LPC) with graphene quantum dots (GQDs) and intrinsic carbon nanowires framework (CNF) is successfully fabricated by a self-template method. The LPC anodes show remarkable Li+ and Na+ storage performance with ultrahigh capacity (738 mA h g-1 for LIBs and 460 mA h g-1 for SIBs at 0.2 C after 300 cycles, 1C≈372 mA h g-1 ) and excellent long-term stability. Structural analysis indicates that the CNFs-supported porous structure and internal GQDs with excellent electrical conductivity contribute significantly to the dominant capacitive storage mechanism in LPC. This work provides new perspectives for developing advanced carbon-based materials for multifunctional batteries with improved stability and utilization of porous carbon frameworks during cycles.

Fast Adiabatic Mode Evolution Assisted 2 × 2 Broadband 3 dB Coupler Using Silicon-on-Insulator Fishbone-like Grating Waveguides.

We report a novel 2 × 2 broadband 3 dB coupler based on fast adiabatic mode evolution with a compact footprint and large bandwidth. The working principle of the coupler is based on the rapid adiabatic evolution of local eigenmodes of fishbone-like grating waveguides. Different from a traditional adiabatic coupling method realized by the slow change of the cross-section size of a strip waveguide, a fishbone waveguide allows faster adiabatic transition with proper structure and segment designs. The presented 3 dB coupler achieves a bandwidth range of 168 nm with an imbalance of no greater than ±0.1 dB only for a 9 µm coupling region which significantly improves existing adiabatic broadband couplers.

Early warning of telecom enterprise customer churn based on ensemble learning.

Analyzing customers' characteristics and giving the early warning of customer churn based on machine learning algorithms, can help enterprises provide targeted marketing strategies and personalized services, and save a lot of operating costs. Data cleaning, oversampling, data standardization and other preprocessing operations are done on 900,000 telecom customer personal characteristics and historical behavior data set based on Python language. Appropriate model parameters were selected to build BPNN (Back Propagation Neural Network). Random Forest (RF) and Adaboost, the two classic ensemble learning models were introduced, and the Adaboost dual-ensemble learning model with RF as the base learner was put forward. The four models and the other four classical machine learning models-decision tree, naive Bayes, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) were utilized respectively to analyze the customer churn data. The results show that the four models have better performance in terms of recall rate, precision rate, F1 score and other indicators, and the RF-Adaboost dual-ensemble model has the best performance. Among them, the recall rates of BPNN, RF, Adaboost and RF-Adaboost dual-ensemble model on positive samples are respectively 79%, 90%, 89%,93%, the precision rates are 97%, 99%, 98%, 99%, and the F1 scores are 87%, 95%, 94%, 96%. The RF-Adaboost dual-ensemble model has the best performance, and the three indicators are 10%, 1%, and 6% higher than the reference. The prediction results of customer churn provide strong data support for telecom companies to adopt appropriate retention strategies for pre-churn customers and reduce customer churn.

Suppressing grating lobes of large-aperture optical phased array with circular array design.

An optical phased array (OPA), especially a two-dimensional (2D) OPA, suffers from the trade-off among steering range, beam width, and the number of antennas. Aperiodic 2D array designs currently aimed to reduce the number of antennas and reduce grating lobes within a wide range fall short when an aperture approaches millimeter size. A circular OPA design is proposed to address this issue. The circular design substantially reduces the number of antennas while achieving the same wide steering range and narrow beam width of optimized aperiodic 2D OPA designs. Its efficient suppression of grating lobes, the key to a wide steering range with minimal number of antennas and large antenna spacing, is theoretically studied and validated by simulation. The novel, to the best of our knowledge, design allows less than 100 antennas, orders of magnitude reduction, for millimeter size aperture OPA designs. It paves the way for commercialization by significantly reducing control complexity and power consumption.

Study on the mechanism of stir-fried Fructus Tribuli in enhancing the essential hypertension treatment by an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy.

Essential hypertension (EH) is a leading cause of cardiovascular morbidity and mortality. Fructus Tribuli (FT), as a traditional medicine, has been frequently used for thousands of years. The crude Fructus Tribuli (CFT), decoction pieces being processed to remove impurities, have been listed as an important medicine for the treatment of hypertension in the elderly. According to the theory of traditional Chinese medicine, the CFT can enhance the EH treatment after being stir-fried into stir-fried Fructus Tribuli (SFT). At present, whether the SFT can enhance the EH treatment and its potential pharmacodynamic substances and mechanism are unknown. In this study, an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy was used. Using male spontaneously hypertensive rats as an experimental model, we compared the therapeutic effects of CFT and SFT on EH. Subsequently, to define the pharmacodynamic material basis of SFT in enhancing the EH treatment, the steroidal saponins (main active components of FT) were selected for spectrum-effect relationship analysis. Furthermore, we applied the joint pathway analysis of network pharmacology and metabolomics to explore the underlying mechanism of SFT in enhancing the EH treatment. Results showed that SFT was better than CFT in the EH treatment. The steroidal saponins transformed by stir-frying were the potential pharmacodynamic substances that SFT could enhance the EH treatment. And the mechanism of action might be associated with regulating glycerophospholipid metabolism and arachidonic acid metabolism, especially arachidonic acid metabolism. This study provided a scientific basis for the clinical use of SFT as an important medicine for the EH treatment.

Network pharmacology-based approach uncovers the pharmacodynamic components and mechanism of Fructus Tribuli for improving endothelial dysfunction in hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT), a traditional Chinese medicinal herbal, has been used for the clinical treatment of cardiovascular diseases for many years and affects vascular endothelial dysfunction (ED) in patients with hypertension. AIM OF THE STUDY: This study aimed to demonstrate the pharmacodynamic basis and mechanisms of FT for the treatment of ED. MATERIALS AND METHODS: The present study used ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze and identify the chemical components of FT. The active components in blood were determined after the oral administration of FT by comparative analysis to blank plasma. Then, based on the active components in vivo, network pharmacology was performed to predict the potential targets of FT in treating ED. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed, and component-target-pathway networks were constructed. Interactions between the major active components and main targets were verified by molecular docking. Moreover, spontaneously hypertensive rats (SHRs) were divided into the normal, model, valsartan, low-dose FT, medium-dose FT, and high-dose FT experimental groups. In pharmacodynamic verification studies, treatment effects on blood pressure, serum markers (nitric oxide [NO], endothelin-1 [ET-1,], and angiotensin Ⅱ [Ang Ⅱ)]) of ED, and endothelial morphology of the thoracic aorta were evaluated and compared between groups. Finally, the PI3K/AKT/eNOS pathway was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot of the thoracic aorta of rats in each group to detect the mRNA expression of PI3K, AKT, and eNOS and the protein expression of PI3K, AKT, p-AKT, eNOS, and p-eNOS. RESULTS: A total of 51 chemical components were identified in FT, and 49 active components were identified in rat plasma. Thirteen major active components, 22 main targets, and the PI3K/AKT signaling pathway were screened by network pharmacology. The animal experiment results showed that FT reduced systolic blood pressure and ET-1 and Ang Ⅱ levels and increased NO levels in SHRs to varying degrees. The therapeutic effects were positively correlated with the oral dose of FT. Hematoxylin-eosin (HE) staining confirmed that FT could alleviate the pathological damage of the vascular endothelium. qRT-PCR and Western blot analysis confirmed that up-regulated expression of the PI3K/AKT/eNOS signaling pathway could improve ED. CONCLUSIONS: In this study, the material basis of FT was comprehensively identified, and the protective effect on ED was confirmed. FT had a treatment effect on ED through multi-component, multi-target, and multi-pathways. It also played a role by up-regulating the PI3K/AKT/eNOS signaling pathway.

VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection.

Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to accelerate neuron apoptosis. The understanding is limited about which key effectors regulate macrophage-neuron crosstalk upon infection. We have used neurotropic-virus-infected murine models to identify that vascular endothelial growth factor receptor 3 (VEGFR-3) is upregulated in the CNS macrophages and that virally infected neurons secrete the ligand VEGF-C. When cultured with VEGF-C-containing supernatants from virally infected neurons, VEGFR-3+ macrophages suppress tumor necrosis factor α (TNF-α) secretion to reduce neuron apoptosis. Vegfr-3ΔLBD/ΔLBD (deletion of ligand-binding domain in myeloid cells) mice or mice treated with the VEGFR-3 kinase inhibitor exacerbate the severity of encephalitis, TNF-α production, and neuron apoptosis post Japanese encephalitis virus (JEV) infection. Activating VEGFR-3 or blocking TNF-α can reduce encephalitis and neuronal damage upon JEV infection. Altogether, we show that the inducible VEGF-C/VEGFR-3 module generates protective crosstalk between neurons and macrophages to alleviate CNS viral infection.

Si Photonics FMCW LiDAR Chip with Solid-State Beam Steering by Interleaved Coaxial Optical Phased Array.

LiDAR has attracted increasing attention because of its strong anti-interference ability and high resolution. Traditional LiDAR systems rely on discrete components and face the challenges of high cost, large volume, and complex construction. Photonic integration technology can solve these problems and achieve high integration, compact dimension, and low-cost on-chip LiDAR solutions. A solid-state frequency-modulated continuous-wave LiDAR based on a silicon photonic chip is proposed and demonstrated. Two sets of optical phased array antennas are integrated on an optical chip to form a transmitter-receiver interleaved coaxial all-solid-state coherent optical system which provides high power efficiency, in principle, compared with a coaxial optical system using a 2 × 2 beam splitter. The solid-state scanning on the chip is realized by optical phased array without a mechanical structure. A 32-channel transmitter-receiver interleaved coaxial all-solid-state FMCW LiDAR chip design is demonstrated. The measured beam width is 0.4° × 0.8°, and the grating lobe suppression ratio is 6 dB. Preliminary FMCW ranging of multiple targets scanned by OPA was performed. The photonic integrated chip is fabricated on a CMOS-compatible silicon photonics platform, providing a steady path to the commercialization of low-cost on-chip solid-state FMCW LiDAR.

A Light/Pressure Bifunctional Electronic Skin Based on a Bilayer Structure of PEDOT:PSS-Coated Cellulose Paper/CsPbBr3 QDs Film.

With the continuous development of electronic skin (e-skin), multifunctional e-skin is approaching, and in some cases even surpassing, the capabilities of real human skin, which has garnered increasing attention. Especially, if e-skin processes eye's function, it will endow e-skins more powerful advantages, such as the vision reparation, enhanced security, improved adaptability and enhanced interactivity. Here, we first study the photodetector based on CsPbBr3 quantum dots film and the pressure sensor based on PEDOT: PSS-coated cellulose paper, respectively. On the base of these two kinds of sensors, a light/pressure bifunctional sensor was successfully fabricated. Finally, flexible bifunctional sensors were obtained by using a flexible interdigital electrode. They can simultaneously detect light and pressure stimulation. As e-skin, a high photosensitivity with a switching ratio of 168 under 405 nm light at a power of 40 mW/cm2 was obtained and they can also monitor human motions in the meantime. Our work showed that the strategy to introduce perovskite photodetectors into e-skins is feasible and may open a new way for the development of flexible multi-functional e-skin.

Efficacy of ultrasound-guided bilateral costal margin block in laparoscopy-assisted gastrectomy: A double-blind randomized trial.

BACKGROUND: Ultrasound-guided costal margin block (CMB) is a superficial and easily applicable technique. The current study aims to investigate its analgesic efficacy in patients undergoing laparoscopy-assisted gastrectomy and describe its feasibility. METHODS: Forty-two patients undergoing laparoscopy-assisted gastrectomy were enrolled in this prospective, double-blind, randomized clinical trial. Patients were randomized to receive standard general anesthesia with (block group, n = 21) or without (control group, n = 21) ultrasound-guided bilateral CMB. The primary outcome was 24-h intravenous morphine equivalents after surgery. Secondary outcomes included consumption of titrated morphine, 24-48 h morphine equivalents, consumption of intraoperative remifentanil, numerical pain rating scale scores, time to first opioid dose, patient satisfaction, adverse effects, and recovery events. RESULTS: The postoperative 24-h morphine equivalents in the block group were significantly reduced compared to the control group (14.4 ± 7.4 mg vs. 29.9 ± 9.8 mg, p < 0.001). Both the titrated morphine consumption in the post-anesthesia care unit (PACU) and intraoperative remifentanil consumption were lower in the block group than in the control group. Patients in the block group had relatively lower average pain scores in PACU and reported more satisfaction with pain relief. Adverse effects and hospital length of stay after surgery were comparable between the two groups (p > 0.05). CONCLUSION: As a novel and easily-performed technique, ultrasound-guided bilateral CMB can reduce opioid consumption in patients undergoing laparoscopy-assisted gastrectomy.

Ideal acoustic quantum spin Hall phase in a multi-topology platform.

Fermionic time-reversal symmetry ([Formula: see text])-protected quantum spin Hall (QSH) materials feature gapless helical edge states when adjacent to arbitrary trivial cladding materials. However, due to symmetry reduction at the boundary, bosonic counterparts usually exhibit gaps and thus require additional cladding crystals to maintain robustness, limiting their applications. In this study, we demonstrate an ideal acoustic QSH with gapless behaviour by constructing a global Tf on both the bulk and the boundary based on bilayer structures. Consequently, a pair of helical edge states robustly winds several times in the first Brillouin zone when coupled to resonators, promising broadband topological slow waves. We further reveal that this ideal QSH phase behaves as a topological phase transition plane that bridges trivial and higher-order phases. Our versatile multi-topology platform sheds light on compact topological slow-wave and lasing devices.

Procoxacin bidirectionally inhibits osteoblastic and osteoclastic activity in bone and suppresses bone metastasis of prostate cancer.

BACKGROUND: Bone is the most common site of metastasis of prostate cancer (PCa). PCa invasion leads to a disruption of osteogenic-osteolytic balance and causes abnormal bone formation. The interaction between PCa and bone stromal cells, especially osteoblasts (OB), is considered essential for the disease progression. However, drugs that effectively block the cancer-bone interaction and regulate the osteogenic-osteolytic balance remain undiscovered. METHODS: A reporter gene system was constructed to screen compounds that could inhibit PCa-induced OB activation from 631 compounds. Then, the pharmacological effects of a candidate drug, Procoxacin (Pro), on OBs, osteoclasts (OCs) and cancer-bone interaction were studied in cellular models. Intratibial inoculation, micro-CT and histological analysis were used to explore the effect of Pro on osteogenic and osteolytic metastatic lesions. Bioinformatic analysis and experiments including qPCR, western blotting and ELISA assay were used to identify the effector molecules of Pro in the cancer-bone microenvironment. Virtual screening, molecular docking, surface plasmon resonance assay and RNA knockdown were utilized to identify the drug target of Pro. Experiments including co-IP, western blotting and immunofluorescence were performed to reveal the role of Pro binding to its target. Intracardiac inoculation metastasis model and survival analysis were used to investigate the therapeutic effect of Pro on metastatic cancer. RESULTS: Luciferase reporter gene consisted of Runx2 binding sequence, OSE2, and Alp promotor could sensitively reflect the intensity of PCa-OB interaction. Pro best matched the screening criteria among 631 compounds in drug screening. Further study demonstrated that Pro effectively inhibited the PCa-induced osteoblastic changes without killing OBs or PCa cells and directly killed OCs or suppressed osteoclastic functions at very low concentrations. Mechanism study revealed that Pro broke the feedback loop of TGF-ß/C-Raf/MAPK pathway by sandwiching into 14-3-3ζ/C-Raf complex and prevented its disassociation. Pro treatment alleviated both osteogenic and osteolytic lesions in PCa-involved bones and reduced the number of metastases of PCa in vivo. CONCLUSIONS: In summary, our study provides a drug screening strategy based on the cancer-host microenvironment and demonstrates that Pro effectively inhibits both osteoblastic and osteoclastic lesions in PCa-involved bones, which makes it a promising therapeutic agent for PCa bone metastasis.

Validation of Layer-By-Layer Coating as a Procedure to Enhance Lactobacillus plantarum Survival during In Vitro Digestion, Storage, and Fermentation.

Probiotics are sensitive to phenolic antibacterial components and the extremely acidic environment of blueberry juices. Layer-by-layer (LbL) coating using whey protein isolate fibrils (WPIFs) and sodium alginate (ALG), carboxymethyl cellulose (CMC), or xanthan gum (XG) was developed to improve the survival rate of Lactobacillus plantarum 90 (LP90) in simulated digestion, storage, and fermented blueberry juices. The LbL-coated LP90 remained at 6.65 log CFU/mL after 48 h of fermentation. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that dense and rough wall networks were formed on the surface of LP90, maintaining the integrity of LP90 cells after the coating. Stability evaluation showed that the LbL-coated LP90 had a much higher survival rate in the processes of simulated gastrointestinal digestion and storage. The formation mechanism of the LbL coating process was further explored, which indicated that electrostatic interactions and hydrogen bonding were involved. The LbL coating approach has great potential to protect and deliver probiotics in food systems.