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Morphogenesis of hair follicles during development and in hair reconstitution assays involves complex interactions between epithelial cells and dermal papilla cells (DPCs). DPCs may be a source of cells for hair regeneration in alopecia patients. Reconstitution of engineered hair follicles requires in vitro culture of trichogenic cells, a three-dimensional scaffolds, and biomolecular signals. However, DPCs tend to lose their biological activity when cultured as trichogenic cells, and scaffolds currently used for hair follicle regeneration lack biological efficiency and biocompatibility. Platelet-rich plasma (PRP) gel forms a three-dimensional scaffold that can release endogenous growth factors, is mitogenic for a variety of cell types and is used in model tissue repair and regeneration systems. We found that 5% activated PRP significantly enhanced cell proliferation and hair-inductive capability of mouse and human DPCs in vitro and promoted mouse hair follicle formation in vivo . PRP also formed a three-dimensional gel after activation. We used PRP gel as a scaffold to form many de novo hair follicles on a plane surface, showing it to be candidate bioactive scaffold capable of releasing endogenous growth factors for cell-based hair follicle regeneration.

The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na + , K + , Mg 2+ and Ca 2+ ), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level. A common approach to design single-molecule switch is to use molecular backbones in response to external stimulus, but often requires complex organic synthesis. Here, Tong et al. show how to in situ control of the molecule-electrode contact using electrochemical gating to realize a reversible switch.

BEST4 is a member of the bestrophin protein family that plays a critical role in human intestinal epithelial cells. However, its role and mechanism in colorectal cancer (CRC) remain largely elusive. Here, we investigated the role and clinical significance of BEST4 in CRC. Our results demonstrate that BEST4 expression is upregulated in clinical CRC samples and its high-level expression correlates with advanced TNM (tumor, lymph nodes, distant metastasis) stage, LNM (lymph node metastasis), and poor survival. Functional studies revealed that ectopic expression of BEST4 promoted CRC cell proliferation and metastasis, whereas the depletion of BEST4 had the opposite effect both in vitro and in vivo. Mechanistically, BEST4 binds to the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K) and promotes p110 kinase activity; this leads to activation of Akt signaling and expression of MYC and CCND1, which are critical regulators of cell proliferation and metastasis. In clinical samples, the expression of BEST4 is positively associated with the expression of phosphorylated Akt, MYC and CCND1. Pharmacological inhibition of Akt activity markedly repressed BEST4-mediated Akt signaling and proliferation and metastasis of CRC cells. Importantly, the interaction between BEST4 and p85α was also enhanced by epidermal growth factor (EGF) in CRC cells. Therapeutically, BEST4 suppression effectively sensitized CRC cells to gefitinib treatment in vivo. Taken together, our findings indicate the oncogenic potential of BEST4 in colorectal carcinogenesis and metastasis by modulating BEST4/PI3K/Akt signaling, highlighting a potential strategy for CRC therapy.

We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for ( ) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for infection. This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups. VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for infection in China.

Background/Aims: The aim of this study was to elucidate how high-mobility group box 1 (HMGB1) exacerbates renal ischemic-reperfusion injury (IRI) by inflammatory and immune responses through the toll-like receptor 4 (TLR4) signaling pathway. Methods: A total of 30 wild-type (WT) mice and 30 TLR4 knockout (TLR4-/-) mice were selected and then randomly assigned to the Sham, I/R or HMGB1 groups. The serum and kidney tissues of all mice were collected 24 h after the perfusion. The fully automatic biochemical detector and ELISA were applied to determine the blood urea nitrogen (BUN) and serum creatinine (Scr) levels, and TNF-α, IL-1β, IL-6, IFN-γ and IL-10 levels, respectively. HE staining was used to evaluate kidney tissue damage, immunofluorescence and immunohistochemical staining were performed to observe CD68 and MPO cell infiltration, and flow cytometry was applied to detect immune cells. qRT-PCR and Western blotting were used to detect the expressions of TLR signaling pathway-related genes and proteins, respectively. Results: Compared with the Sham group, the levels of BUN, Scr, TNF-α, IL-1β, IL-6, IFN-γ and IL-10, kidney tissue damage score, CD68 and MPO cell infiltration, the numbers of immune cells, and the expressions of TLR signaling pathway-related genes and proteins in the I/R and HMGB1 groups were significantly up-regulated. In the I/R and HMGB1 groups, the levels of BUN and Scr, TNF-α, IL-1β, IL-6 and IFN-γ, kidney tissue damage score, CD68 and MPO cell infiltration, immune cell numbers, and TLR signaling pathway-related gene and protein expressions in the WT mice were all higher than those in the TLR4-/- mice, but IL-10 level was significantly lower. Similarly, all aforementioned indexes but IL-10 level in the WT and TLR4-/- mice were higher in the HMGB1 group than in the I/R group. Conclusion: Our study indicated that the up-regulation of HMGB1 could exacerbate renal IRI by stimulating inflammatory and immune responses through the TLR4 signaling pathway.c

Single-molecule recognition and detection with the highest resolution measurement has been one of the ultimate goals in science and engineering. Break junction techniques, originally developed to measure single-molecule conductance, recently have also been proven to have the capacity for the label-free exploration of single-molecule physics and chemistry, which paves a new way for single-molecule detection with high temporal resolution. In this review, we outline the primary advances and potential of the STM break junction technique for qualitative identification and quantitative detection at a single-molecule level. The principles of operation of these single-molecule electrical sensing mainly in three regimes, ion, environmental pH and genetic material detection, are summarized. It clearly proves that the single-molecule electrical measurements with break junction techniques show a promising perspective for designing a simple, label-free and nondestructive electrical sensor with ultrahigh sensitivity and excellent selectivity.

To address the issue of not having enough labeled fault data for planetary gearboxes in actual production, this research develops a simulation data-driven deep transfer learning fault diagnosis method that applies fault diagnosis knowledge from a dynamic simulation model to an actual planetary gearbox. Massive amounts of different fault simulation data are collected by creating a dynamic simulation model of a planetary gearbox. A fresh deep transfer learning network model is built by fusing one-dimensional convolutional neural networks, attention mechanisms, and domain adaptation methods. The network model is used to learn domain invariant features from simulated data, thereby enabling fault diagnosis on real data. The fault diagnosis experiment is verified by using the Drivetrain Diagnostics Simulator test bench. The validity of the proposed means is evaluated by comparing the diagnostic accuracy of various means on various diagnostic tasks.

Raman spectroscopy unleashed Surface-enhanced Raman scattering (SERS) spectroscopy is a powerful analytical technique able to detect substances down to single molecule level. Its applications are limited, however, because to realize a substantial Raman signal requires metal substrates that either have roughened surfaces or take the form of nanoparticles. An innovative approach is now demonstrated, where the substance under investigation, on a generic substrate, is covered by a layer of 'smart dust' consisting of gold nanoparticles coated by an ultrathin insulating shell of silica or alumina. The nanoparticles provide Raman signal amplification, and the coating keeps them separate from each other and from the probed substance. The new technique, termed SHINERS (shell-isolated nanoparticle-enhanced Raman spectroscopy), is demonstrated by probing pesticide residues on the surfaces of yeast cells and citrus fruits. It could be useful in materials science and the life sciences, as well as for the inspection of food safety, drugs, explosives and environmental pollutants. Surface-enhanced Raman scattering is a powerful spectroscopy technique that can be used to study substances down to the level of single molecules. But the practical applications have been limited by the need for metal substrates with roughened surfaces or in the form of nanoparticles. Here a new approach — shell-insulated nanoparticle-enhanced Raman spectroscopy — is described, and its versatility demonstrated with numerous test substances. Surface-enhanced Raman scattering (SERS) is a powerful spectroscopy technique that can provide non-destructive and ultra-sensitive characterization down to single molecular level, comparable to single-molecule fluorescence spectroscopy 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 . However, generally substrates based on metals such as Ag, Au and Cu, either with roughened surfaces or in the form of nanoparticles, are required to realise a substantial SERS effect, and this has severely limited the breadth of practical applications of SERS. A number of approaches have extended the technique to non-traditional substrates 14 , 16 , 17 , most notably tip-enhanced Raman spectroscopy (TERS) 18 , 19 , 20 where the probed substance (molecule or material surface) can be on a generic substrate and where a nanoscale gold tip above the substrate acts as the Raman signal amplifier. The drawback is that the total Raman scattering signal from the tip area is rather weak, thus limiting TERS studies to molecules with large Raman cross-sections. Here, we report an approach, which we name shell-isolated nanoparticle-enhanced Raman spectroscopy, in which the Raman signal amplification is provided by gold nanoparticles with an ultrathin silica or alumina shell. A monolayer of such nanoparticles is spread as ‘smart dust’ over the surface that is to be probed. The ultrathin coating keeps the nanoparticles from agglomerating, separates them from direct contact with the probed material and allows the nanoparticles to conform to different contours of substrates. High-quality Raman spectra were obtained on various molecules adsorbed at Pt and Au single-crystal surfaces and from Si surfaces with hydrogen monolayers. These measurements and our studies on yeast cells and citrus fruits with pesticide residues illustrate that our method significantly expands the flexibility of SERS for useful applications in the materials and life sciences, as well as for the inspection of food safety, drugs, explosives and environment pollutants.

The success of different heterogeneous strategies of organometallic catalysts has been demonstrated to achieve high selectivity and activity in photo/electrocatalysis. However, yielding their catalytic mechanisms at complex molecule‐electrode and electrochemical interfaces remains a great challenge. Herein, shell‐isolated nanoparticle‐enhanced Raman spectroscopy is employed to elucidate the dynamic process, interfacial structure, and intermediates of copper hydroxide‐2‐2′ bipyridine on Au electrode ((bpy)Cu(OH)2/Au) during the oxygen evolution reaction (OER). Direct Raman molecular evidences reveal that the interfacial (bpy)Cu(OH)2 oxidizes into Cu(III) and bridges to Au atoms via oxygenated species, forming (bpy)Cu(III)O2‐Au with oxygen‐bridged binuclear metal centers of Cu(III)‐O‐Au for the OER. As the potential further increases, Cu(III)‐O‐Au combines with surface hydroxyl groups (*OH) to form the important intermediate of Cu(III)‐OOH‐Au, which then turns into Cu(III)‐OO‐Au to release O2. Furthermore, in situ electrochemical impedance spectroscopy proves that the Cu(III)‐O‐Au has lower resistance and faster mass transport of hydroxy to enhance OER. Theoretical calculations reveal that the formation of Cu(III)‐O‐Au significantly modify the elementary reaction steps of the OER, resulting in a lower potential‐determining step of ≈0.58 V than that of bare Au. This work provides new insights into the OER mechanism of immobilized‐molecule catalysts for the development and application of renewable energy conversion devices. In situ Raman monitoring of an electrochemically induced interfacial oxygen‐bridged Cu(III)‐O‐Au binuclear center in heterogenized molecular catalysts, could combine surface hydroxyl groups to form the important intermediate of Cu(III)‐OOH‐Au, which then turns into Cu(III)‐OO‐Au to release O2. This significantly modifies the elementary reaction steps and lowers the overpotential for oxygen evolution reaction.

This article takes the linear inclined vibrating screen (TLIVS) as the research object, establishes a spatial 6-degree-of-freedom dynamic model of TLIVS, and verifies the correctness of the established model through comparison between real experiments and simulation experiments. Steady-state response of TLIVS is solved by numerical analysis method, The influence of each degree of freedom acting separately on the screening process of TLIVS was explored using the discrete element method. The results indicate that x-direction translation movement mainly promotes the dispersion of the mixture, and y-direction translation movement mainly increases the velocity of the mixture towards the outlet. z-direction translation movement mainly causes the mixture to stratify. Rotation in the x-direction accumulates the mixture in the middle of the screen surface, rotation in the y-direction helps to disperse the material at the inlet, and rotation in the z-direction may cause blockage of the mixture.