Coupling control technology of anchoring and unloading in deep intense-mining and large-deformation roadway: a case study.

In order to control the deformation of surrounding rock in deep high-stress and intense-mining roadways, taking a deep coal roadway with continuous deformation as an example, the characteristics of crustal stress, coal strength, and mining influence of roadway are obtained by underground tests. The combined failure mechanism of coal roadway surrounding-rock is revealed by differential stress of deep and shallow anchor cables. We propose that the improvement of surrounding rock control for coal roadway is adopting the coupling control technology of anchoring and unloading. The stress distribution and evolution laws of lateral surrounding rock of unloading holes are obtained by numerical simulation and theoretical calculation, and reasonable unloading-hole spacing of 4.0 m is comprehensively determined. A mechanical model of roadway roof beam under fixed support at both ends is constructed and the important role of anchor cable beam-truss in controlling the stability of coal roadway is obtained. The rationality of coupling control technology of anchoring and unloading and parameters has been verified by engineering test and mine pressure observation, providing technical references for surrounding rock control in deep intense-mining and large-deformation roadways.

Construction of Fu brick tea polysaccharide-cold plasma modified alginate microgels for probiotic delivery: Enhancing viability and colonization.

Emerging food processing technologies provide broader avenues for enhancing probiotic delivery systems. In this study, the new Fu brick tea polysaccharide (FBTP) was extracted and combined with cold plasma-modified alginate nano-montmorillonite (AMT) to prepare microgels by ionic gelation to improve the viability of encapsulated Lactobacillus kefiranofaciens JKSP109. Results showed that cold plasma treatment for 3 min changed the surface charge of AMT biopolymer solution, and FBTP addition reduced the particle size to the lowest of 223 ± 5.50 nm. Morphological analysis showed that the AMT treated with cold plasma for 3 min and FBTP (C3AMT + FBTP) formed a dense microgel through electrostatic interaction, and the probiotics were randomly distributed in their internal polysaccharide network, as well as the interlayer and surrounding of nanoparticles. The probiotics immobilized in C3AMT + FBTP microgel exhibited the highest viability (8.48 ± 0.03 log CFU/g) and colonic colonization after exposure to simulated gastrointestinal conditions. In addition, the good antioxidant activity of FBTP reduced the loss of probiotic viability during storage, with only 2.58 log CFU/g decreased after 4 weeks. Therefore, such probiotic products enriched with natural bioactive ingredients can be developed as a potential functional food additive.

Improved phase-to-height mapping method combine with device attitude.

Phase-to-height mapping is one of the important processes in three dimensional phase measurement profilometry. But, in traditional phase-to-height mapping method, the measurement accuracy is affected by device attitude, so it needs saving a large amount of mapping equations to achieve high-quality phase-to-height mapping. In order to improve that, this paper proposes an improved phase-to-height mapping method combine with device attitude. Firstly, we get the unwrapped phase of the target. Then, using generalized regression neural network is used to reduce the offset of phase information at the same height due to the randomness of device attitude. Last, the phase-to-height mapping is completed by substituting the unwrapped phase (the difference between having detected object and no detected object) of eliminate the offset into improved phase-to-height mapping method. Experimental results show that the proposed method could achieve high-quality phase-to-height mapping with less mapping equation and less memory space. Compared with the nonlinear phase-to-height mapping method (probabilistic neural network to eliminate phase offset), its accuracy is improved by 44.30%. Compared with the nonlinear phase-to-height mapping method (radial basis function neural network to eliminate phase offset), the accuracy is improved by 39.58%.

Preparation and characterization of pectin-alginate-based microbeads reinforced by nano montmorillonite filler for probiotics encapsulation: Improving viability and colonic colonization.

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.

ZnO-incorporated alginate assemblies: Tunable pH-responsiveness and improved drug delivery for cancer therapy.

Delivering drugs selectively to tumor tissues is a significant challenge in cancer therapy, and pH-responsive polymeric assemblies have shown great potential in achieving this goal. In this study, we developed a pH-responsive alginate-based assemblies, called (amine-modified ZnO)-oxidized alginate-PEG ((ZnO-N)-OAl-PEG), for selective drug delivery in cancer treatment. The incorporation of ZnO-N nanoparticles into the alginate-based assemblies enables pH-responsiveness and maintains stability under physiological conditions. At an acidic pH, (ZnO-N)-OAl-PEG disassembles due to the conversion of ZnO to Zn2+, which triggers the unloading of doxorubicin (DOX) from the imine bond between DOX and alginate. This unloading results in the death of cancer cells and inhibition of tumor growth. The anticancer efficacy of (DOX/ZnO-N)-OAl-PEG was demonstrated in vitro and in vivo, providing promising prospects for cancer treatment based on ZnO-induced pH-responsiveness. These findings may also inspire the development of advanced drug delivery systems (DDSs) for cancer therapy.

Probiotic-loaded edible films made from proteins, polysaccharides, and prebiotics as a quality factor for minimally processed fruits and vegetables: A review.

Minimally processed fruits and vegetables (MPFVs) are gaining popularity in households because of their freshness, convenience, and rapid consumption, all of which align with today's busy lifestyles. However, their exposure of large surface areas during peeling and slicing can result in contamination by foodborne pathogens and spoilage bacteria, posing potential food safety concerns. In addition, enzymatic browning of MPFVs can significantly reduce their consumer appeal. Therefore, it is necessary to adopt certain methods to protect MPFVs. Recent studies have shown that utilizing biopolymer-based edible films containing probiotics is a promising approach to preserving MPFVs. These active food packaging films exhibit barrier function, antioxidant function, and antimicrobial function while protecting the viability of probiotics, which is essential to maintain the nutritional value and quality of MPFVs. This paper reviews microbial contamination in MPFVs and the preparation of probiotic-loaded edible films with common polysaccharides (alginate, gellan gum, and starch), proteins (zein, gelatin, and whey protein isolate), prebiotics (oligofructose, inulin, and fructooligosaccharides). It also explores the potential application of probiotic-loaded biopolymer films/coatings on MPFVs, and finally examines the practical application requirements from a consumer perspective.

Heavy metal contamination and risk assessment in winter jujube (Ziziphus jujuba Mill. cv. Dongzao).

Winter jujube (Ziziphus jujuba Mill. cv. Dongzao) is a major fresh-eating jujube fruit with various important nutrients for humans. It can absorb heavy metals from polluted air, water and soils and applied pesticides, which may pose potential threats to consumers. Here, to evaluate the content of heavy metals in winter jujube and systematically evaluate the potential risks, we collected 212 winter jujube samples from four main producing areas in China and determined the contents of eight heavy metals (Cd, Cr, Pb, Ni, Cu, Zn, As, and Mn) using inductively coupled plasma mass spectrometer (ICP-MS). Based on the integrated pollution index (IPI) evaluation standard, more than 99.06% of samples were at safe levels. Moreover, clustering analysis divided the eight heavy metals into four groups, namely Cr/Ni, Cd/Pb, Cu/Mn/Zn, and As. Importantly, none of the analyzed heavy metals posed risks to adults as indicted by the average carcinogenic and non-carcinogenic risks. Notably, Cr and Cd could pose low carcinogenic risks to children (≤12 age group) when their concentration reached the 90th percentile. This study systematically assessed the health risks associated with heavy metal intake through winter jujube consumption and highlighted the necessity of constant heavy metal monitoring in winter jujube.

A Cre knockin mouse reveals specific expression of Agouti gene in mesenchymal lineage cells in multiple organs and provides a unique tool for conditional gene targeting.

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.

Expression dynamics of lymphoid enhancer-binding factor 1 in terminal Schwann cells, dermal papilla, and interfollicular epidermis.

BACKGROUND: Transcription factor lymphoid enhancer-binding factor 1 (LEF1) is a downstream mediator of the Wnt/ß-catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation, and differentiation. RESULTS: Here, we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with T-cell factor 3 (TCF3) overexpression. CONCLUSION: We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells.

Large-scale isolation of functional dermal papilla cells using novel surface marker LEPTIN Receptor.

Dermal papilla (DP) cells regulate hair follicle epithelial cells and melanocytes by secreting functional factors, playing a key role in hair follicle morphogenesis and hair growth. DP cells can reconstitute new hair follicles and induce hair regeneration, providing a potential therapeutic strategy for treating hair loss. However, current methods for isolating DP cells are either inefficient (physical microdissection) or only applied to genetically labeled mice. We systematically screened for the surface proteins specifically expressed in skin DP using mRNA expression databases. We identified two antibodies against receptors LEPTIN Receptor (LEPR ) and Scavenger Receptor Class A Member 5 (SCARA5) which could specifically label and isolate DP cells by flow cytometry from mice back skin at the growth phase. The sorted LEPR+ cells maintained the DP characteristics after culturing in vitro, expressing DP marker alkaline phosphatase and functional factors including RSPO1/2 and EDN3, the three major DP secretory factors that regulate hair follicle epithelial cells and melanocytes. Furthermore, the low-passage LEPR+ DP cells could reconstitute hair follicles on nude mice using chamber graft assay when combined with epithelial stem cells. The method of isolating functional DP cells we established here lays a solid foundation for developing DP cell-based therapy.

Fabrication of hyaluronic acid-based micelles with glutathione-responsiveness for targeted anticancer drug delivery.

Hyaluronic acid (HA), a natural polymer, has gained much attention recently because of its good biocompatibility and extensive availability. Herein, a novel drug delivery system based on hyaluronic acid-tetraphenyl ethylene conjugate (HA-SS-TPE) with glutathione (GSH)-responsiveness for targeted drug delivery is designed. During the self-assembly of HA-SS-TPE, doxorubicin (DOX) is loaded to form DOX-loaded polymeric micelles. These as-prepared DOX-loaded polymeric micelles not only exhibit fluorescent emission, but also fast glutathione-triggered dissociation to unload DOX by responding to tumor microenvironments. In-vitro investigations showed that the DOX-loaded polymeric micelles presented a higher intracellular release ratio in CD44-positive cells (ES2 and Hela) than in CD44-negative cells (MCF-7 and L929). Notably, in vivo investigations showed that DOX@HA-SS-TPE significantly suppressed tumor growth. As a result, such a GSH-responsive drug delivery system with fluorescent feature provides a potential treatment for CD44-overexpressing cancers.

Simultaneous Rapid Detection of Aflatoxin B1 and Ochratoxin A in Spices Using Lateral Flow Immuno-Chromatographic Assay.

Spices are susceptible to contamination by aflatoxin B1 (AFB1) and ochratoxin A (OTA), which are both mycotoxins with high toxicity and carcinogenicity. In this study, we aimed to develop an immuno-chromatographic strip test for the simultaneous quantification of AFB1 and OTA in spices by spraying the coupled antigens AFB1-ovalbumin (AFB1-OVA) and OTA-ovalbumin (OTA-OVA) on a nitrocellulose membrane. The test strip had high sensitivity, good specificity, and strong stability. The detection limits of these two mycotoxins in Chinese prickly ash, pepper, chili, cinnamon, and aniseed were 5 µg/kg. The false positivity rate was 2%, and the false negativity rate was 0%. The maximum coefficient of variation was 4.28% between batches and 5.72% within batches. The average recovery rates of AFB1 and OTA in spices were 81.2-113.7% and 82.2-118.6%, respectively, and the relative standard deviation (RSD) was <10%. The actual sample detection was consistent with high performance liquid chromatography analysis results. Therefore, the immuno-chromatographic test strips developed in this study can be used for the on-site simultaneous detection of AFB1 and OTA in spices. This method would allow the relevant regulatory agencies to strengthen supervision in an effort to reduce the possible human health hazards of such contaminated spices.

Identity, Synthesis, and Cytotoxicity of Forchlorfenuron Metabolites in Kiwifruit.

Forchlorfenuron (CPPU) is a plant growth regulator widely used in kiwifruit production. Although research on the toxicological and environmental effects of CPPU is well-established, the nature and toxicological properties of its metabolites are much less well-known. Using high resolution mass spectrometry and nuclear magnetic resonance, the CPPU previously unidentified metabolites in Xuxiang and Jinyan kiwifruit were identified as N-(2-chloro-4-pyridinyl)-N'-(2-hydroxy-4-methoxyphenyl)-urea (metabolite 1) and N-phenyl-N'-4-pyridinylurea (metabolite 2, CAS: 1932-35-0). Their structures were confirmed by synthesis (metabolite 1) and by comparison with a commercial standard (metabolite 2). Quantitative studies demonstrate that CPPU and its metabolites are mainly retained in the kiwifruit peel, while the content is dependent on the nature of the peel surface, with the smoother peel of Jinyan kiwifruit retaining smaller amounts of the compound. Cell viability experiments in Caco2 and Lo2 cells show that the metabolites may have a lower cytotoxicity compared to the parent compound CPPU.

Metallic Oxide-Induced Self-Assembly of Block Copolymers to Form Polymeric Hybrid Micelles with Tunable Stability for Tumor Microenvironment-Responsive Drug Delivery.

Since block copolymers are able to self-assemble into various polymeric architectures, it is intriguing to explore a unique self-assembly strategy for polymers. Two different metallic oxides [manganese dioxide (MnO2) and zinc oxide (ZnO)] are displayed herein to demonstrate this self-assembly mechanism of polymers. In situ generation of metallic oxides induces self-assembly of block copolymers to form polymeric hybrid micelles with tunable stability in aqueous solutions. These final ZnO-cross-linked polymeric micelles exhibited a high drug loading capacity of 0.41 mg mg-1 toward doxorubicin (DOX), whereas DOX-loaded ZnO-cross-linked polymeric micelles could be broken down into Zn2+ and polymer scraps, which facilitated drug release in tumor microenvironments. Both in vitro and in vivo investigations showed that the drug-loaded ZnO-cross-linked polymeric micelles effectively suppressed tumor growth. Accordingly, the present study demonstrates a novel strategy of polymer self-assembly for fabricating polymeric architectures that can potentially provide insight for developing other polymeric architectures.

Use of pH-Active Catechol-Bearing Polymeric Nanogels with Glutathione-Responsive Dissociation to Codeliver Bortezomib and Doxorubicin for the Synergistic Therapy of Cancer.

Synergistic therapy holds promising potential in cancer treatment. Here, the inclusion of catechol moieties, a disulfide cross-linked structure, and pendent carboxyl into the network of polymeric nanogels with glutathione (GSH)-responsive dissociation and pH-sensitive release is first disclosed for the codelivery of doxorubicin (DOX) and bortezomib (BTZ) in synergistic cancer therapy. The pendent carboxyl groups and catechol moieties are exploited to absorb DOX through electrostatic interaction and conjugate BTZ through boronate ester, respectively. Both electrostatic interactions and boronate ester are stable at neutral or alkaline pH, while they are instable in an acidic environment to further recover the activities of BTZ and DOX. The polymeric nanogels possess a superior stability to prevent the premature leakage of drugs in a physiological environment, while their structure is destroyed in response to a typical endogenous stimulus (GSH) to unload drugs. The dissociation of the drug-loaded nanogels accelerates the intracellular release of DOX and BTZ and further enhances the therapeutic efficacy. In vitro and in vivo investigations revealed that the dual-drug loaded polymeric nanogels exhibited a strong ability to suppress tumor growth. This study thus proposes a new perspective on the production of multifunctional polymeric nanogels through the introduction of different functional monomers.

Effects of different pesticides treatments on the nutritional quality of kiwifruit.

Pesticides are widely used in the process of kiwifruit growth to promote fruit expansion. This study was aimed to assess the effects of pesticides on the quality of kiwifruit by applying high and normal concentrations of forchlorfenuron (CPPU) and thidiazuron (TDZ) to "Xuxiang" (XX) green kiwifruit and "Jinyan" (JY) gold kiwifruit. Sixty kiwifruit trees were used to comprehensively evaluate the effects on the pulp and whole kiwifruit. In addition to the weight gain effect and basic physical-chemical properties (vitamin C, total protein, glucose and fructose, organic acids), the main nutritional qualities (in vitro and cellular antioxidant activity (CAA), and dietary minerals) were also evaluated. The vitamin C content of XX was not affected by pesticides, but the use of CPPU reduced vitamin C of JY pulp by 23% (p < 0.05). Pesticides did not reduce the antioxidant values of XX pulp in vitro but significantly reduced CAA values (32%-47%). In JY pulp, pesticides treatments had no significant effect on antioxidant values in vitro except that CPPU treatments significantly reduced the ferric reducing antioxidant power (FRAP) value by 21% (p < 0.05). Reasonable use of pesticides can effectively improve taste of kiwifruit, increasing kiwifruit weight and the content of certain nutrients. PRACTICAL APPLICATION: Based on observed changes in nutritional components, CPPU may be more suitable for XX while TDZ may be more suitable for JY. The significance of this study may affect kiwifruit farmers and ultimately help improve the sensory quality of kiwifruit.

Stimuli-responsive nanocarriers for therapeutic applications in cancer.

Cancer has become a very serious challenge with aging of the human population. Advances in nanotechnology have provided new perspectives in the treatment of cancer. Through the combination of nanotechnology and therapeutics, nanomedicine has been successfully used to treat cancer in recent years. In terms of nanomedicine, nanocarriers play a key role in delivering therapeutic agents, reducing severe side effects, simplifying the administration scheme, and improving therapeutic efficacies. Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years. Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy. Notably, stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents, when compared with systemic chemotherapy, and achieve controlled drug release at tumor sites. Therefore, the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy. This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers, in the last few decades. These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli. Furthermore, nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer, which will provide us with better choices for cancer therapy.

Optimized mesoporous silica nanoparticle-based drug delivery system with removable manganese oxide gatekeeper for controlled delivery of doxorubicin.

Rapid progress has been made for mesoporous silica nanoparticle (MSN) in recent years; however, efforts to fabricate MSN with adjustable size have been met with limited advancement in drug delivery, especially for the synthesis of MSN with adjustable size in the range of 150-300 nm. Herein we report the construction of a series of MSNs with adjustable specific surface area, size, and pore structure, depending on the different silicon monomers selected. The optimized MSN showed large specific surface area and appropriate size distribution for efficiently anchoring doxorubicin (DOX) through the imine linkage formed. Based on the remarkable features of the unique MSN, a novel MSN-based drug delivery system was prepared through the introduction of polydopamine/manganese oxide (PDA/MnO2) coating, which reduced the premature leakage of drugs in physiological environments, and yet facilitated drug release when destroyed by responding to endogenous glutathione (GSH) at the tumor sites. Notably, the transformation of MnO2 to Mn2+ resulted in the collapse of the PDA/MnO2 coating, which facilitated drug release and therefore indicated the controlled release feature. It was demonstrated that the drug-loaded MSN-based drug delivery system delivered drugs into cancer cells and showed effective inhibition against cancer cell growth. These results suggested that the emergence of MSN with adjustable size can expand the application of MSN in drug delivery.

Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma.

BACKGROUND: Cyclooxygenase 2 (COX-2) is an inducible enzyme which promotes tumorigenesis in many types of cancers. Genetic knockout of COX-2 significantly suppresses the tumorigenesis of skin squamous cell carcinoma (SCC). However, COX-2 inhibitor treatment only showed mild to moderate inhibition on SCC in previous reports. The aim of this study is to solve this contradiction and to re-evaluate the therapeutic potential of targeting COX-2 in SCC. METHODS: COX-2 was knocked down by shRNA in two different SCC cell lines, A431 and SCC-13. The cells proliferation and migration capacity were evaluated by cell growth curves and monolayer scratch assay, respectively. Cancer cells with COX-2 knockdown were also xenografted into Balb/c nude mice and tumor growth curves were recorded over time. In addition, we changed the drug administration route and intraperitoneally injected COX-2 inhibitor celecoxib into mice to evaluate its anti-cancer activity. RESULTS: Knockdown of COX-2 exhibited mild or even no effect on cell proliferation and migration in two different SCC cell lines in vitro. However, when cancer cells were xenografted into nude mice, knockdown of COX-2 significantly suppressed proliferation of cancer cells in tumors. At last, intraperitoneal injection instead of oral administration of COX-2 inhibitor celecoxib potently suppressed tumor growth. CONCLUSIONS: Our results indicate that COX-2 might impact on the interaction between cancer cells and surrounding microenvironments rather than on cancer cells directly, and demonstrate that targeting COX-2 is a very promising therapeutic approach for SCC treatment.