HGF Facilitates the Repair of Spinal Cord Injuries by Driving the Chemotactic Migration of MSCs Through the ß-Catenin/TCF4/Nedd9 Signaling Pathway.

Transplanted mesenchymal stem cells (MSCs) can significantly aid in repairing spinal cord injuries (SCI) by migrating to and settling at the injury site. However, this process is typically inefficient, as only a small fraction of MSCs successfully reach the target lesion area. During SCI, the increased expression and secretion of hepatocyte growth factor (HGF) act as a chemoattractant that guides MSC migration. Nonetheless, the precise mechanisms by which HGF influences MSC migration are not fully understood. This study focused on unraveling the molecular pathways that drive MSC migration towards the SCI site in response to HGF. It was found that HGF can activate ß-catenin signaling in MSCs either by phosphorylating LRP6 or by suppressing GSK3ß phosphorylation through the AKT and ERK1/2 pathways, or by enhancing the expression and nuclear translocation of TCF4. This activation leads to elevated Nedd9 expression, which promotes focal adhesion formation and F-actin polymerization, facilitating chemotactic migration. Transplanting MSCs during peak HGF expression in injured tissues substantially improves nerve regeneration, reduces scarring, and enhances hind limb mobility. Additionally, prolonging HGF release can further boost MSC migration and engraftment, thereby amplifying regenerative outcomes. However, inhibiting HGF/Met or interfering with ß-catenin or Nedd9 signaling significantly impairs MSC engraftment, obstructing tissue repair and functional recovery. Together, these findings provide a theoretical basis and practical strategy for MSC transplantation therapy in SCI, highlighting the specific molecular mechanisms by which HGF regulates ß-catenin signaling in MSCs, ultimately triggering their chemotactic migration.

Direct conversion of human umbilical cord mesenchymal stem cells into dopaminergic neurons for Parkinson's disease treatment.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits due to the depletion of nigrostriatal dopamine. Stem cell differentiation therapy emerges as a promising treatment option for sustained symptom relief. In this study, we successfully developed a one-step differentiation system using the YFBP cocktail (Y27632, Forskolin, SB431542, and SP600125) to effectively convert human umbilical cord mesenchymal stem cells (hUCMSCs) into dopaminergic neurons without genetic modification. This approach addresses the challenge of rapidly and safely generating functional neurons on a large scale. After a 7-day induction period, over 80 % of the cells were double-positive for TUBB3 and NEUN. Transcriptome analysis revealed the dual roles of the cocktail in inducing fate erasure in mesenchymal stem cells and activating the neuronal program. Notably, these chemically induced cells (CiNs) did not express HLA class II genes, preserving their immune-privileged status. Further study indicated that YFBP significantly downregulated p53 signaling and accelerated the differentiation process when Pifithrin-α, a p53 signaling inhibitor, was applied. Additionally, Wnt/ß-catenin signaling was transiently activated within one day, but the prolonged activation hindered the neuronal differentiation of hUCMSCs. Upon transplantation into the striatum of mice, CiNs survived well and tested positive for dopaminergic neuron markers. They exhibited typical action potentials and sodium and potassium ion channel activity, demonstrating neuronal electrophysiological activity. Furthermore, CiNs treatment significantly increased the number of tyrosine hydroxylase-positive cells and the concentration of dopamine in the striatum, effectively ameliorating movement disorders in PD mice. Overall, our study provides a secure and reliable framework for cell replacement therapy for Parkinson's disease.

Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Management in Intertrochanteric Fractures: A Randomized Controlled Study.

BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.

Magnitude and Spatial Distribution Control of the Supercurrent in Bi2O2Se-Based Josephson Junction.

Many proposals for exploring topological quantum computation are based on superconducting quantum devices constructed on materials with strong spin-orbit coupling (SOC). For these devices, full control of both the magnitude and the spatial distribution of the supercurrent is highly demanded, but has been elusive up to now. We constructed a proximity-type Josephson junction on nanoplates of Bi2O2Se, a new emerging semiconductor with strong SOC. Through electrical gating, we show that the supercurrent can be fully turned ON and OFF, and its real-space pathways can be configured either through the bulk or along the edges. Our work demonstrates Bi2O2Se as a promising platform for constructing multifunctional hybrid superconducting devices as well as for searching for topological superconductivity.

Lysophosphatidic acid guides the homing of transplanted olfactory ensheathing cells to the lesion site after spinal cord injury in rats.

Olfactory ensheathing cells (OECs) are ideal candidates for cell-based therapies aimed at repairing spinal cord injury (SCI). Accurate targeting of OECs to the lesion site is critical to reconstructing the impaired nervous system. However, the key factors guiding the homing of transplanted OECs to the damaged area after SCI are still unclear. Here, we demonstrate that lysophosphatidic acid (LPA) can significantly facilitate the homing of OECs after SCI in rats. First, we found that OECs exhibited a robust chemotaxis response to LPA in vitro, with LPAR1 being predominant receptor expressed on OECs. We further found that ß-catenin signaling plays an important role in LPA-induced OEC migration. Moreover, silencing LPAR1 not only abolished the migration of OECs but also prevented ERK1/2 phosphorylation and ß-catenin activation, suggesting that LPAR1 ligation serves to activate the ERK1/2 and ß-catenin pathways in LPA-induced OEC chemotactic migration. Finally, cell transplantation experiments confirmed that endogenous LPA, which was observed to be produced at the lesion site after SCI in rat, is a key chemokine that facilitates OEC migration to the injury center. Collectively, our data provide a further description of the homing effects of LPA and a mechanism by which transplanted OECs migrate to the injured area after SCI in rats.

Evaluation of the Efficacy of a Lactobacilli-Based Teat Detergents for the Microbiota of Cows Teats Using an Untargeted Metabolomics Approach.

Teat cleaning pre- and post-milking is important for the overall health and hygiene of dairy cows. The purpose of this research was to evaluate the effectiveness of a teat detergents based on lactic acid bacteria according to changes in somatic cell count and cow-milk metabolites. Sixty-nine raw milk samples were collected from 11 Holstein-Friesian cows in China during 12 days of teat cleaning. An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry-based untargeted metabolomic approach was applied to detect metabolomic differences after treatment with lactic acid bacteria and chemical teat detergents in cows with subclinical mastitis. The results suggest that the lactobacilli-based teat detergents could reduce somatic cell count and improve microhabitat of cow teat apex by adjusting the composition of metabolites. Furthermore, the somatic cell count could be decreased significantly within 10 days following the cleaning protocol. Lactic acid bacteria have the potential to be applied as a substitution to teat chemical detergents before and after milking for maintenance of healthy teats and breasts. Further, larger scale validation work is required to support the findings of the current study.

Clinical effects of resurfacing fingertip amputations in long fingers using homodigital dorsal neurofascial broaden pedicle island flaps.

The use of homodigital dorsal neurofascial broaden pedicle island flaps (HDNBPIF) to treat fingertip amputations is an ongoing research topic. Here, we evaluated the clinical effects of resurfacing fingertip amputations in long fingers using HDNBPIF. Seventeen patients with 18 long fingers were treated with HDNBPIF from December 2018 to May 2021. Total active motion (TAM) scores, Semmes Weinstein monofilament (SWM) test, static 2PD test, visual analogue scale (VAS), Vancouver scar scales (VSS), and quick DASH scores were evaluated at 12-25 months postoperation. The aesthetic satisfaction of the patients was estimated subjectively using a 5-point Likert scale. The mean defect size was 1.11 × 1.13 cm and mean flap size was 1.32 × 1.32 cm. All flaps survived and the mean TAM of injured fingers was 255.6° (Contralateral side: 268.4°, p < 0.05). Mean SWM score in the flap was 3.90 g, and 3.22 g in the donor zone. Mean static 2PD discrimination in the flap was 5.61 mm and 4.33 mm in the donor zone. Mean quick Dash scores were 5.81 whereas Mean VAS score in the flap was 0.7 and 0.2 in the donor site. Vancouver scar scales at the donor and recipient sites ranged from 0 to 2. At the end of the follow-up, all patients reported good aesthetic appearance and curative effects. These results show that HDNBPIF is a promising strategy that achieves good curative effects and recovery of fingertip functions.Type of Study and Level of Evidence: Therapeutic IV.

In vitro biocompatibility study of EDC/NHS cross-linked silk fibroin scaffold with olfactory ensheathing cells.

In this paper, we investigated silk fibroin (SF) cross-linked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and its biocompatibility with olfactory ensheathing cells (OECs). After cross-linked with different concentrations of EDC/NHS solutions, SF scaffolds were analyzed by different techniques such as scanning electron microscopy, Fourier transform infrared spectra, x-ray diffraction, tensile machine and water contact angle assay. As to their structures, we found 4.5% EDC/NHS cross-linked SF possessed a more significant increase of ß-sheet and a decrease of α-helix than 1.5% group. These changes helped SF achieve excellent mechanical properties. While more remarkable improvement of hydrophilicity was seen in 1.5% EDC/NHS treated SF. Immunofluorescence, MTT, Annexin-V/PI and ELISA analysis were then conducted to determine the states and functions of OECs on the scaffolds. OECs on 4.5% EDC/NHS cross-linked SF seemed insufficient to spread, and the proliferation was limited on 4 and 6 days. Moreover, 4.5% EDC/NHS exerted adverse effects on cell survival and nerve growth factor (NGF) secretion at day 4, but not 1.5% EDC/NHS. Taken together, SF scaffolds showed improved physical and hydrophilic properties through cross-linking. 1.5% EDC/NHS cross-linked SF scaffolds showed significant advantages between mechanical property and the states and functions with OECs, which has the potential to be used for neural repairing.

Aharonov-casher effect in Bi2Se3 square-ring interferometers.

Electrical control of spin dynamics in Bi(2)Se(3) was investigated in ring-type interferometers. Aharonov-Bohm and Altshuler-Aronov-Spivak resistance oscillations against a magnetic field, and Aharonov-Casher resistance oscillations against the gate voltage were observed in the presence of a Berry phase of π. A very large tunability of spin precession angle by the gate voltage has been obtained, indicating that Bi(2)Se(3)-related materials with strong spin-orbit coupling are promising candidates for constructing novel spintronic devices.

Strong and tunable spin--orbit coupling of one-dimensional holes in Ge/Si core/shell nanowires.

We investigate the low-temperature magneto-transport properties of individual Ge/Si core/shell nanowires. Negative magneto-conductance was observed, which is a signature of one-dimensional weak antilocalization of holes in the presence of strong spin--orbit coupling. The temperature and back gate dependences of phase coherence length, spin--orbit relaxation time, and background conductance were studied. Specifically, we show that the spin--orbit coupling strength can be modulated by more than five folds with an external electric field. These results suggest the Ge/Si nanowire system possesses strong and tunable spin--orbit interactions and may serve as a candidate for spintronics applications.

Phase Transition and Superconductivity Enhancement in Se-Substituted MoTe2 Thin Films.

Consecutively tailoring few-layer transition metal dichalcogenides MX2 from 2H to Td phase may realize the long-sought topological superconductivity in a single material system by incorporating superconductivity and the quantum spin Hall effect together. Here, this study demonstrates that a consecutive structural phase transition from Td to 1T' to 2H polytype can be realized by increasing the Se concentration in Se-substituted MoTe2 thin films. More importantly, the Se-substitution is found to dramatically enhance the superconductivity of the MoTe2 thin film, which is interpreted as the introduction of two-band superconductivity. The chemical-constituent-induced phase transition offers a new strategy to study the s+- superconductivity and the possible topological superconductivity, as well as to develop phase-sensitive devices based on MX2 materials.

Transport evidence of asymmetric spin-orbit coupling in few-layer superconducting 1Td-MoTe2.

Two-dimensional transition metal dichalcogenides MX2 (M = W, Mo, Nb, and X = Te, Se, S) with strong spin-orbit coupling possess plenty of novel physics including superconductivity. Due to the Ising spin-orbit coupling, monolayer NbSe2 and gated MoS2 of 2H structure can realize the Ising superconductivity, which manifests itself with in-plane upper critical field far exceeding Pauli paramagnetic limit. Surprisingly, we find that a few-layer 1Td structure MoTe2 also exhibits an in-plane upper critical field which goes beyond the Pauli paramagnetic limit. Importantly, the in-plane upper critical field shows an emergent two-fold symmetry which is different from the isotropic in-plane upper critical field in 2H transition metal dichalcogenides. We show that this is a result of an asymmetric spin-orbit coupling in 1Td transition metal dichalcogenides. Our work provides transport evidence of a new type of asymmetric spin-orbit coupling in transition metal dichalcogenides which may give rise to novel superconducting and spin transport properties.

Experimental observation of the quantum anomalous Hall effect in a magnetic topological insulator.

The quantized version of the anomalous Hall effect has been predicted to occur in magnetic topological insulators, but the experimental realization has been challenging. Here, we report the observation of the quantum anomalous Hall (QAH) effect in thin films of chromium-doped (Bi,Sb)2Te3, a magnetic topological insulator. At zero magnetic field, the gate-tuned anomalous Hall resistance reaches the predicted quantized value of h/e(2), accompanied by a considerable drop in the longitudinal resistance. Under a strong magnetic field, the longitudinal resistance vanishes, whereas the Hall resistance remains at the quantized value. The realization of the QAH effect may lead to the development of low-power-consumption electronics.

Strong superconducting proximity effect in pb-bi(2)te(3) hybrid structures.

To study the interface between a conventional superconductor and a topological insulator, we fabricated Pb-Bi(2)Te(3)-Pb lateral and sandwiched junctions, and performed electron transport measurements down to low temperatures. The results show that there is a strong superconducting proximity effect between Bi(2)Te(3) and Pb, as that a supercurrent can be established along the thickness direction of the Bi(2)Te(3) flakes (100~300 nm thick) at a temperature very close to the superconducting T(c) of Pb. Moreover, a Josephson current can be established over several microns in the lateral direction between two Pb electrodes on the Bi(2)Te(3 )surface. We have further demonstrated that superconducting quantum interference devices can be constructed based on the proximity-effect-induced superconductivity. The critical current of the devices exhibits s-wave-like interference and Fraunhofer diffraction patterns. With improved designs, Josephson devices of this type would provide a test-bed for exploring novel phenomena such as Majorana fermions in the future.

Real-time detection of electron tunnelling in a quantum dot.

Nanostructures in which strong (Coulomb) interactions exist between electrons are predicted to exhibit temporal electronic correlations. Although there is ample experimental evidence that such correlations exist, electron dynamics in engineered nanostructures have been observed directly only on long timescales. The faster dynamics associated with electrical currents or charge fluctuations are usually inferred from direct (or quasi-direct) current measurements. Recently, interest in electron dynamics has risen, in part owing to the realization that additional information about electronic interactions can be found in the shot noise or higher statistical moments of a direct current. Furthermore, interest in quantum computation has stimulated investigation of quantum bit (qubit) readout techniques, which for many condensed-matter systems ultimately reduces to single-shot measurements of individual electronic charges. Here we report real-time observation of individual electron tunnelling events in a quantum dot using an integrated radio-frequency single-electron transistor. We use electron counting to measure directly the quantum dot's tunnelling rate and the occupational probabilities of its charge state. Our results provide evidence in favour of long (10 micros or more) inelastic scattering times in nearly isolated dots.