Flexible silk-fibroin-based microelectrode arrays for high-resolution neural recording.

High-precision neural recording plays a pivotal role in unraveling the intricate mechanisms that underlie information transmission of the nervous system, raising increasing interest in the development of implantable microelectrode arrays (MEAs). The challenge lies in providing a truly soft, highly conductive and low-impedance neural interface for precise recording of the electrophysiological signals of individual neurons or neural networks. Herein, by implementing a novel topological regulation strategy of silk fibroin (SF) crosslinking, we prepared a flexible, hydrophilic, and biocompatible MEA substrate, facilitating a biocompatible neural interface that minimizes mechanical mismatch with biological tissues. Additionally, we established a strategy involving screen-printing combined with post-coating to prepare MEAs with high conductivity, low impedance and high capacitance, by coating PEDOT:PSS on titanium carbide (Ti3C2) microarrays. The Ti3C2 nanosheets, as the conductive track of the MEAs, avoided the charge drifting associated with metals and facilitated the processing of the MEAs. Further coating PEDOT:PSS on the electrode points reduced the impedance 100-fold, from 105 to 103 Ω. Experimental validation confirmed the superior electrophysiological signal recording capabilities of the SF-based MEA (SMEA) in peripheral and cerebral nerves with a much higher signal-to-noise ratio (SNR) of 20. In particular, we achieved high-precision recording of the action potential (AP) induced by flash visual stimulation, demonstrating high performance in weak signal recording. In summary, the development of SMEA provides a robust foundation for future investigations into the mechanisms and principles of neural circuit information transmission in complex nervous systems.

Red-light-excited TiO2/Bi2S3 heterojunction nanotubes and photoelectric hydrogels mediate epidermal-neural network reconstruction in deep burns.

Inspired by the strong light absorption of carbon nanotubes, we propose a fabrication approach involving one-dimensional TiO2/Bi2S3 QDs nanotubes (TBNTs) with visible red-light excitable photoelectric properties. By integrating the construction of heterojunctions, quantum confinement effects, and morphological modifications, the photocurrent reached 9.22 µA/cm2 which is 66 times greater than that of TiO2 nanotubes (TNTs). Then, a red light-responsive photoelectroactive hydrogel dressing (TBCHA) was developed by embedding TBNTs into a collagen/hyaluronic acid-based biomimetic extracellular matrix hydrogel with good biocompatibility, aiming to promote wound healing and skin function restoration. This approach is primarily grounded in the recognized significance of electrical stimulation in modulating nerve function and immune responses. Severe burns are often accompanied by extensive damage to epithelial-neural networks, leading to a loss of excitatory function and difficulty in spontaneous healing, while conventional dressings inadequately address the critical need for nerve reinnervation. Furthermore, we highlight the remarkable ability of the TBCHA photoelectric hydrogel to promote the reinnervation of nerve endings, facilitate the repair of skin substructures, and modulate immune responses in a deep burn model. This hydrogel not only underpins wound closure and collagen synthesis but also advances vascular reformation, immune modulation, and neural restoration. This photoelectric-based therapy offers a robust solution for the comprehensive repair of deep burns and functional tissue regeneration. STATEMENT OF SIGNIFICANCE: We explore the fabrication of 1D TiO2/Bi2S3 nanotubes with visible red-light excitability and high photoelectric conversion properties. By integrating heterojunctions, quantum absorption effects, and morphological modifications, the photocurrent of TiO2/Bi2S3 nanotubes could reach 9.22 µA/cm², which is 66 times greater than that of TiO2 nanotubes under 625 nm illumination. The efficient red-light excitability solves the problem of poor biosafety and low tissue penetration caused by shortwave excitation. Furthermore, we highlight the remarkable ability of the TiO2/Bi2S3 nanotubes integrated photoelectric hydrogel in promoting the reinnervation of nerve endings and modulating immune responses. This work proposes an emerging therapeutic strategy of remote, passive electrical stimulation, offering a robust boost for repairing deep burn wounds.

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/ß-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of "three more and one less," reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/ß-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

Chronic Kidney Disease Induces Cognitive Impairment in the Early Stage.

OBJECTIVE: Previous research indicates a link between cognitive impairment and chronic kidney disease (CKD), but the underlying factors are not fully understood. This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early- and late-stage CKD models in Sprague-Dawley rats. METHODS: The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery. Histopathologic examinations were conducted to examine renal and hippocampal damage. Real-time PCR, Western blotting analysis, and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor (BDNF), choline acetyltransferase (ChAT), and synaptophysin (SYP). RESULTS: Compared with the control rats, the rats with early-stage CKD exhibited mild renal damage, while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage. The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats, with further deterioration observed in the rats with late-stage CKD. Additionally, we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD, which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD. CONCLUSION: These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly. In addition, the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.

[Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism].

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 µg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION: The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

Hydrogen-bonding topological remodeling modulated ultra-fine bacterial cellulose nanofibril-reinforced hydrogels for sustainable bioelectronics.

Bacterial cellulose (BC) with its inherent nanofibrils framework is an attractive building block for the fabrication of sustainable bioelectronics, but there still lacks an effective and green strategy to regulate the hydrogen-bonding topological structure of BC to improve its optical transparency and mechanical stretchability. Herein, we report an ultra-fine nanofibril-reinforced composite hydrogel by utilizing gelatin and glycerol as hydrogen-bonding donor/acceptor to mediate the rearrangement of the hydrogen-bonding topological structure of BC. Attributing to the hydrogen-bonding structural transition, the ultra-fine nanofibrils were extracted from the original BC nanofibrils, which reduced the light scattering and endowed the hydrogel with high transparency. Meanwhile, the extracted nanofibrils were connected with gelatin and glycerol to establish an effective energy dissipation network, leading to an increase in stretchability and toughness of hydrogels. The hydrogel also displayed tissue-adhesiveness and long-lasting water-retaining capacity, which acted as bio-electronic skin to stably acquire the electrophysiological signals and external stimuli even after the hydrogel was exposing to air condition for 30 days. Moreover, the transparent hydrogel could also serve as a smart skin dressing for optical identification of bacterial infection and on-demand antibacterial therapy after combined with phenol red and indocyanine green. This work offers a strategy to regulate the hierarchical structure of natural materials for designing skin-like bioelectronics toward green, low cost, and sustainability.

Whole transcriptome sequencing and competitive endogenous RNA regulation network construction analysis in benzo[a]pyrene-treated breast cancer cells.

Breast cancer is the most common malignant tumor in women worldwide, and environmental pollutants are considered to be risk factors. Currently, most studies into benzo[a]pyrene (B[a]P)-induced breast cancer focus on biological effects such as proliferation, invasion, and metastasis, DNA damage, estrogen receptor (ER)-related molecular mechanisms, oxidative damage, and other metabolic pathways. This study aims to provide insights into the role of B[a]P in breast cancer development through RNA-seq and bioinformatics analysis and construction of a competing endogenous RNA (ceRNA) regulatory network. By analyzing RNA-seq results, we identified 144 differentially-expressed circRNAs, 69 differentially-expressed lncRNAs, 20 differentially-expressed miRNAs, and 212 differentially-expressed mRNAs. Following on, we analyzed the gene ontology (GO) and KEGG enrichment functions of the differentially-expressed RNAs. In addition, the protein-protein interaction (PPI) network was mapped for differentially-expressed mRNAs. Subsequently, we constructed ceRNA networks, one of which consisted of 45 dysregulated circRNAs, 11 miRNAs, and 9 mRNAs, and a second consisted of 40 lncRNAs, 11 miRNAs, and 9 mRNAs. Finally, 6 circRNAs, 4 lncRNAs, 1 miRNA, and 4 mRNAs were randomly selected for quantitative real-time PCR verification. PCR results were further verified by Western blotting assays. These results show that the expression level of differentially-expressed RNA was consistent with the sequencing data, and the Western blotting results were highly consistent with the PCR results, confirming that the sequencing result was very reliable. This study systematically explores the ceRNA atlas of differentially-expressed genes related to B[a]P exposure in breast cancer cells, providing new insights into mechanisms of environmental pollutants in breast cancer.

One-Pot Synthesis of Bi2 S3 /TiO2 /rGO Heterostructure with Red Light-Driven Photovoltaic Effect for Remote Electrotherapy-Assisted Wound Repair.

The past decades have witnessed the rational design of novel functional nanomaterials and the potential to revolutionize many applications. With the increasing focus on electronic biological processes, novel photovoltaic nanomaterials are highly expectable for empowering new therapeutic strategies such as establishing a link between endogenous electric field (EEF) and electrotherapy. Compared to traditional invasive stimulation, the light-initiating strategy has the advantages of non-invasion, non-power supply, and precise controllability. Whereas, common photoactivated materials require short-wavelength light excitation accompanied by poor tissue penetration and biohazard. Herein, by the construction of p-n heterostructured Bi2 S3 /TiO2 /rGO (BTG) nanoparticles, broadener light absorption and higher light conversion than regular UV excitation are realized. Simultaneously, the photoelectric performance of BTG heterostructure, as well as the synergistic effect of Bi2 S3 morphology, are revealed. Besides, the rationally designed biomimetic hydrogel matrix consisting of collagen and hyaluronic acid provides appropriate bioactivity, interface adhesion, mechanical matching, and electron transfer. Therefore, the photovoltaic BTG-loaded matrix provides a platform of light-driven electrical stimulation, coupling the EEF to modulate the electrophysiological and regeneration microenvironment. The implementation of photoelectric stimulation holds broad prospects for non-drug therapy and electrical-related biological process modulation including osseointegration, nerve regeneration, electronic skin, and wound healing.

[Therapeutic Effect of Single Intramuscular Administration of Recombinant Human Thrombopoietin on Rhesus Monkeys with Acute radiation Sickness].

OBJECTIVE: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60Co γ-ray, and provide experimental basis for clinical treatment of similar patients. METHODS: Fourteen adult rhesus monkeys were irradiated with 60Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 µg/kg group (n=4) and rhTPO 10 µg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 µg/kg（0.1 ml/kg） and rhTPO 10 µg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. RESULTS: After total body irradiation with 5.0 Gy60Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 µg/kg or 10 µg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 µg/ kg was better. CONCLUSION: A single injection of rhTPO 5 µg/ kg or 10 µg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

[Effect of Interleukin-6 Gene Deletion on Radiation-Induced Mouse Hematopoietic Injury and Relative Mechanism].

OBJECTIVE: To study the effect of interleukin-6 (IL-6) gene deletion on radiation-induced hematopoietic injury in mice and relative mechanism. METHODS: Before and after whole body 60Co γ-ray irradiation, it was analyzed and compared that the difference of peripheral hemogram, bone marrow hematopoietic stem and progenitor cells conts in IL-6 gene knockout (IL-6-/-) and wild-type (IL-6+/+) mice and serum IL-6 and G-CSF expression levels in above- mentioned mouse were detected. Moreover, 30 days survival rate of IL-6-/- and IL-6+/+ mice after 8.0 Gy γ-ray irradiation were analyzed. RESULTS: IL-6 levels in serum of IL-6+/+ and IL-6-/- mice were respectively (98.95±3.85) pg/ml and (18.36±5.61) pg/ml, which showed a significant statistical differences (P<0.001). There were no significant differences of peripheral blood cell counts and G-CSF level in serum between IL-6+/+ and IL-6-/- mice before irradiation (P>0.05). However, the number of leukocytes, neutrophils, lymphocytes, monocytes, platelets in peripheral blood and G-CSF level in serum of IL-6-/- mice were significantly decreased at 6 h after 8.0 Gy γ-ray irradiation compared with that of IL-6+/+ mice. On days 30 after 8.0 Gy γ-ray irradiation, the survival rate of IL-6+/+ and IL-6-/- mice was 62.5% and 12.5%, and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days, respectively. On days 14 after 6.5 Gy γ-ray irradiation, bone marrow nucleated cells in IL-6+/+ and IL-6-/- mice were respectively (10.0±1.2)×106 and (8.3±2.2)×106 per femur. Compared with IL-6+/+ mice, the proportion of Lin-Sca-1-c-kit+ (LK) in bone marrow of IL-6-/- mice had no significant change (P>0.05), but the proportion of Lin-Sca-1+c-kit+ (LSK) was significantly decreased (P<0.05). CONCLUSION: IL-6 plays an obvious role in regulating hematopoietic radiation injury, and IL-6 deficiency can inhibit the radiation-induced increase of endogenous G-CSF level in serum, aggravates the damage of mouse hematopoietic stem cells（HSC） and the reduction of mature blood cells in peripheral blood caused by ionizing irradiation, resulting in the shortening of the survival time and significant decrease of the survival rate of mice exposed to lethal dose radiation.

A Bioactive and Photoresponsive Platform for Wireless Electrical Stimulation to Promote Neurogenesis.

Delivering electrical signals to neural cells and tissue has attracted increasing attention in the treatment of nerve injuries. Unlike traditional wired electrical stimulation, wireless and remote light stimulation provides less invasive and longer-lasting interfaces, holding great promise in the treatment of nerve injuries and neurodegenerative diseases, as well as human-computer interaction. Additionally, a bioactive matrix that bridges the injured gap and induces nerve regeneration is essential for injured nerve repair. However, it is still challenging to construct a 3D biomimetic cell niche with optoelectrical responsiveness. Herein, a bioactive platform for remote and wireless optoelectrical stimulation is established by incorporating hydrophilic poly(3-hexylthiophene) nanoparticles (P3HT NPs) into a biomimetic hydrogel matrix. Moreover, the hydrogel matrix is modified by varying the composition and/or the crosslinking degree to meet the needs of different application scenarios. When exposed to pulsed green light, P3HT NPs in hydrogels convert light signals into electrical signals, resulting in the generation of tens of picoampere photocurrent, which is proved to promote the growth of cortical neurons that covered by hydrogels and the neuronal differentiation of bone marrow mesenchymal stem cells (BMSCs) encapsulated in hydrogels. This work is of great significance for the design of next-generation neural electrodes and scaffolds.

Transplantation for EASL-CLIF and APASL acute-on-chronic liver failure (ACLF) patients: The TEA cohort to evaluate long-term post-Transplant outcomes.

Background: The forecast accuracy of the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) and Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) criteria in assessing long-term outcomes after liver transplantation (LT) is still unclear, especially when the staging of the two standards is inconsistent. Methods: A retrospective cohort (NCT05036031) including 565 patients from January 2015 to June 2021 was conducted. The 28 and 90 days, 1- and 3-years overall survival (OS) after LT were compared between different grades. Findings: Total of 162 (28.7%) and 230 (40.7%) patients met the ACLF standards. In the EASL-CLIF criteria, the 3-year OS rates were 83·0%, 80·3%, and 69·8% for ACLF1-3, respectively. In the APASL criteria, the 3-year OS rates were 85·7% for APASL ACLF Research Consortium (AARC)-1, similar to ACLF-1. The 3-year OS rates were 84·5% for AARC-2, which were slightly better than ACLF-2. Regarding AARC-3, the 3-year OS rate was 5·8% higher than ACLF-3. For patients who met neither set of criteria for ACLF, the 3-year OS rates were 89·8%. The multivariate analysis showed that alanine aminotransferase >100 U/L, respiration failure, and cerebral failure were independent risk factors for post-LT death. Interpretation: This study provides the first large-scale long-term follow-up data in Asia. Both criteria showed favorable distinguishing ability for post-LT survival. Patients with ACLF had a higher post-LT mortality risk, and ACLF-3 and AARC-3 correlated with significantly greater mortality. Funding: National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording.

A flexible non-transient electrical platform that can realize bidirectional neural communication from living tissues is of great interest in neuroscience to better understand basic neuroscience and the nondrug therapy of diseases or disorders. The development of soft, biocompatible, and conductive neural interface with mechanical coupling and efficient electrical exchange is a new trend but remains a challenge. Herein, we designed a multifunctional neural electrical communication platform in the form of a mechanically compliant, electrically conductive, and biocompatible hydrogel electrode. Silk fibroin (SF) obtained from Bombyx Mori cocoons was compounded with aldehyde-hyaluronic acid (HA-CHO) with a dynamic network to delay or interrupt the ß-sheet-induced hardening of SF chains, resulting in the fabrication of a hydrogel matrix that is mechanically matched to biological tissues. Moreover, the incorporation of functionalized carbon nanotubes (CNTs) facilitated interaction and dispersion and enabled the formation of a hydrogel electrode with a high-current percolation network, thus contributing toward improving the electrical properties in terms of conductivity, impedance, and charge storage capabilities. These advances allow high-efficiency stimulation and the recording of neural signals during in vivo implantation. Overall, a wide range of animal experiments demonstrate that the platform exhibits minimal foreign body responses, thus showing it to be a promising electrophysiology interface for potential applications in neuroscience.

Root Na+ Content Negatively Correlated to Salt Tolerance Determines the Salt Tolerance of Brassica napus L. Inbred Seedlings.

Soil salinization is a major environmental stressor that reduces the growth and yield of crops. Maintaining the balance of ions under salinity is vital for plant salt tolerance; however, little is known about the correlation between the salt tolerance of crops and the ion contents of their roots and shoots. Here, we investigated the poorly understood salt-tolerance mechanisms, particularly regarding ion contents (particularly Na+), in Brassica napus subsp. napus L., an agriculturally important species. Twenty B. napus inbred lines were randomly chosen from five salt-tolerance categories and treated with increasing concentrations of NaCl (0-200 mmol) for this work. We found that the root Na+ content is the most correlated limiting factor for the salt tolerance of B. napus; the higher the salt tolerance, the lower the root Na+ content. Correspondingly, the Ca2+/Na+ and K+/Na+ ratios of the roots were highly correlated with B. napus salt tolerance, indicating that the selective absorption ability of these ions by the roots and their translocation to the shoots play a pivotal role in this trait. These data provide a foundation for the further study of the molecular mechanisms underlying salt tolerance and for breeding salt-tolerant B. napus cultivars.

A photoelectric effect integrated scaffold for the wireless regulation of nerve cellular behavior.

Electrical signals are a key factor to promote nerve cell neurogenesis. However, the traditionally used exogenous electrical stimulus mode requires additional equipment and complicated wiring, which is very inconvenient. To date, it has been challenging to provide electrical signals to nerve cells in a non-invasive and wireless controllable way, accompanied by the construction of a biomimetic cell microenvironment for supporting nerve cell survival and functional expression. Herein, a new concept of a light-powered oriented bioactive scaffold for remote and wireless electrical stimulation has been developed. By combining electrospinning and electrospraying, the highly oriented polycaprolactone (PCL) microfibrous scaffold with co-sprayed bioactive collagen and photoelectric poly-3-hexylthiophene nanoparticles (P3HT NPs) was obtained, named as PCL-P3HT-Col, which exhibits a considerable photoelectric effect and vital characteristics of the native nerve extracellular matrix. The results show that a photocurrent ranging from 20-80 pA was obtained by changing the light density of a 530 nm green light source. Further, the specific photoelectric conversion effect trigged by the P3HT NPs promotes the oriented elongation and up-regulation of neuronal characteristic factors in rat pheochromocytoma cells (PC12 cells), which is controlled by L-type voltage-gated calcium channel (L-VGCC) activity. This study provides new insights to engineer self-powered scaffolds towards the non-invasive and wireless-controlled stimulation mode of a variety of cells and tissues.

Semiconvertible Hyaluronic Hydrogel Enabled Red-Light-Responsive Reversible Mechanics, Adhesion, and Self-Healing.

Photoresponsive supramolecular hydrogels based on the host-guest interaction between cyclodextrin (CD) and azobenzene (Azo) are highly favored in "on-demand" biological applications. Nevertheless, most Azo/CD-based hydrogels are UV-responsive, exhibiting poor tissue penetrability and potential cytotoxicity; more importantly, the complete gel-sol transition under irradiation makes intelligent systems unstable. Here, we report a red-light-responsive semiconvertible hydrogel based on tetra-ortho-methoxy-substituted Azo (mAzo)- and CD-functionalized hyaluronic acid (HA). By integrating red-shifted-photoisomerized mAzo with HA, a biocompatible 625 nm-light-responsive polymeric guest with strengthened hydrogen bonding and weakened photoisomerization was synthesized. Upon alternating irradiation, mAzo-HA/CD-HA hydrogels obtained here exhibited reversible mechanical and structural dynamics, while avoiding complete gel-sol transition. This improved semiconvertibility remedies the lack of macroscopic resilience for dynamic system so as to endow supramolecular hydrogels with spatial-temporal mechanics, self-healing, and adhesion. Together with excellent cytocompatibility and manufacturability, these hydrogels show potential advantages in tissue engineering, especially for the regeneration of functional multi-tissue complex.

Aldehyde-methacrylate-hyaluronan profited hydrogel system integrating aligned and viscoelastic cues for neurogenesis.

Either oriented architecture or viscoelasticity is pivotal to neurogenesis, thus, native neural extracellular matrix derived-hyaluronan hydrogels with nano-orientation and viscoelasticity recapitulated might be instructive for neurogenesis, however it is still unexploited. Herein, based on aldehyde-methacrylate difunctionalized hyaluronan, by integrating imine kinetic modulation and microfluidic biofabrication, we construct a hydrogel system with orthogonal viscoelasticity and nano-topography. We then find the positive synergy effects of matrix nano-orientation and viscoelasticity not only on neurites outgrowth and elongation of neural cells, but also on neuronal differentiation of stem cells. Moreover, by implanting viscoelastic and nano-aligned hydrogels into lesion sites, we demonstrate the enhanced repair of spinal cord injury, including ameliorated pathological microenvironment, facilitated endogenous neurogenesis and functional axons regeneration as well as motor function restoration. This work supplies universal platform for preparing neuronal inducing hyaluronan-based hydrogels which might serve as promising therapeutic strategies for nerve injury.

Chemical Compounds, Antioxidant Activities, and Inhibitory Activities Against Xanthine Oxidase of the Essential Oils From the Three Varieties of Sunflower (Helianthus annuus L.) Receptacles.

Background/Aim: Essential oils of sunflower receptacles (SEOs) have antibacterial and antioxidant potential. However, the differences of biological activities from the different varieties of sunflowers have not been studied till now. The purpose of this study was to compare the differences of chemical compounds, antioxidant activities, and inhibitory activities against xanthine oxidase (XO) of SEOs from the three varieties of sunflowers including LD5009, SH363, and S606. Methods: SEOs were extracted by using the optimal extraction conditions selected by response surface methodology (RSM). Chemical compounds of SEOs were identified from the three varieties of sunflowers by gas chromatography-mass spectrometry (GC-MS). Antioxidant activities of SEOs were detected by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and iron ion reduction ability. Inhibitory activities of SEOs against XO were measured by using UV spectrophotometer. XO inhibitors were selected from the main chemical compounds of SEOs by the high-throughput selections and molecular simulation docking. Results: The extraction yields of SEOs from LD5009, SH363, and S606 were 0.176, 0.319, and 0.580%, respectively. A total of 101 chemical compounds of SEOs were identified from the three varieties of sunflowers. In addition, the results of inhibitory activities against XO showed that SEOs can reduce uric acid significantly. Eupatoriochromene may be the most important chemical compounds of SEOs for reducing uric acid. The results of antioxidant activities and inhibitory activities against XO showed that SEOs of LD5009 had the strongest antioxidant and XO inhibitory activities. The Pearson correlation coefficient (r > 0.95) showed that γ-terpinene, (E)-citral, and L-Bornyl acetate were highly correlated with the antioxidant activities and XO inhibitory ability. Conclusion: SEOs had antioxidant activities and XO inhibitory ability. It would provide more scientific information for utilization and selection of varieties of sunflowers, which would increase the food quality of sunflowers and incomes of farmers.

Antioxidative and Conductive Nanoparticles-Embedded Cell Niche for Neural Differentiation and Spinal Cord Injury Repair.

Following spinal cord injury (SCI), the transmission of electrical signals is interrupted, and an oxidative microenvironment is generated, hindering nerve regeneration and functional recovery. The strategies of regulating oxidative pathological microenvironment while restoring endogenous electrical signal transmission hold promise for SCI treatment. However, challenges are still faced in simply fabricating bioactive scaffolds with both antioxidation and conductivity. Herein, aiming to construct an antioxidative and conductive microenvironment for nerve regeneration, the difunctional polypyrrole (PPy) nanoparticles were developed and incorporated into bioactive collagen/hyaluronan hydrogel. Owing to the embedded PPy in hydrogel, the encapsulated bone marrow mesenchymal stem cells (BMSCs) can be protected from oxidative damage, and their neuronal differentiation was promoted by the synergy between conductivity and electrical stimulation, which is proved to be related to PI3K/Akt and the mitogen-activated protein kinase (MAPK) pathway. In SCI rats, the BMSC-laden difunctional hydrogel restored the transmission of bioelectric signals and inhibited secondary damage, thereby facilitating neurogenesis, resulting in prominent nerve regeneration and functional recovery. Overall, taking advantage of a difunctional nanomaterial to meet two essential requirements in SCI repair, this work provides intriguing insights into the design of biomaterials for nerve regeneration and tissue engineering.

Neoadjuvant Programmed Cell Death 1 (PD-1) Inhibitor Treatment in Patients With Hepatocellular Carcinoma Before Liver Transplant: A Cohort Study and Literature Review.

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.