AKT1 phosphorylates RBM17 to promote Sox2 transcription by modulating alternative splicing of FOXM1 to enhance cancer stem cell properties in colorectal cancer cells.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic-induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17-mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1-RBM17-FOXM1-Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation.

BACKGROUND/AIMS: Vagus nerve stimulation (VNS) suppresses arrhythmic activity and minimizes cardiomyocyte injury. However, how VNS affects angiogenesis/arteriogenesis in infarcted hearts, is poorly understood. METHODS: Myocardial infarction (MI) was achieved by ligation of the left anterior descending coronary artery (LAD) in rats. 7 days after LAD, stainless-steel wires were looped around the left and right vagal nerve in the neck for vagus nerve stimulation (VNS). The vagal nerve was stimulated with regular pulses of 0.2ms duration at 20 Hz for 10 seconds every minute for 4 hours, and then ACh levels by ELISA in cardiac tissue and serum were evaluated for its release after VNS. Three and 14 days after VNS, Real-time PCR, immunostaining and western blot were respectively used to determine VEGF-A/B expressions and α-SMA- and CD31-postive vessels in VNS-hearts with pretreatment of α7-nAChR blocker mecamylamine (10 mg/kg, ip) or mACh-R blocker atropine (10 mg/kg, ip) for 1 hour. The coronary function and left ventricular performance were analyzed by Langendorff system and hemodynamic parameters in VNS-hearts with pretreatment of VEGF-A/B-knockdown or VEGFR blocker AMG706. Coronary arterial endothelial cells proliferation, migration and tube formation were evaluated for angiogenesis following the stimulation of VNS in coronary arterial smooth muscle cells (VSMCs). RESULTS: VNS has been shown to stimulate VEGF-A and VEGF-B expressions in coronary arterial smooth muscle cells (VSMCs) and endothelial cells (ECs) with an increase of α-SMA- and CD31-postive vessel number in infarcted hearts. The VNS-induced VEGF-A/B expressions and angiogenesis were abolished by m-AChR inhibitor atropine and α7-nAChR blocker mecamylamine in vivo. Interestingly, knockdown of VEGF-A by shRNA mainly reduced VNS-mediated formation of CD31+ microvessels. In contrast, knockdown of VEGF-B powerfully abrogated VNS-induced formation of α-SMA+ vessels. Consistently, VNS-induced VEGF-A showed a greater effect on EC tube formation as compared to VNS-induced VEGF-B. Moreover, VEGF-A promoted EC proliferation and VSMC migration while VEGF-B induced VSMC proliferation and EC migration in vitro. Mechanistically, vagal neurotransmitter acetylcholine stimulated VEGF-A/B expressions through m/nACh-R/PI3K/Akt/Sp1 pathway in EC. Functionally, VNS improved the coronary function and left ventricular performance. However, blockade of VEGF receptor by antagonist AMG706 or knockdown of VEGF-A or VEGF-B by shRNA significantly diminished the beneficial effects of VNS on ventricular performance. CONCLUSION: VNS promoted angiogenesis/arteriogenesis to repair the infracted heart through the synergistic effects of VEGF-A and VEGF-B.

Ag/alginate nanofiber membrane for flexible electronic skin.

Flexible electronic skin has stimulated significant interest due to its widespread applications in the fields of human-machine interactivity, smart robots and health monitoring. As typical elements of electrical skin, the fabrication process of most pressure sensors combined nanomaterials and PDMS films are redundant, expensive and complicated, and their unknown biological toxicity could not be widely used in electronic skin. Hence, we report a novel, cost-effective and antibacterial approach to immobilizing silver nanoparticles into-electrospun Na-alginate nanofibers. Due to the unique role of carboxyl and hydroxyl groups in Na-alginate, the silver nanopaticles with 30 nm size in diameter were uniformly distributed inside and outside the alginate nanofibers, which obtained pressure sensor shows stable response, including an ultralow detection limited (1 pa) and high durability (>1000 cycles). Notably, the pressure sensor fabricated by these Ag/alginate nanofibers could not only follow human respiration but also accurately distinguish words like 'Nano' and 'Perfect' spoke by a tester. Interestingly, the pixelated sensor arrays based on these Ag/alginate nanofibers could monitor distribution of objects and reflect their weight by measuring the different current values. Moreover, these Ag/alginate nanofibers exhibit great antibacterial activity, implying the great potential application in artificial electronic skin.

Bimetallic metal-organic framework aerogels supported by aramid nanofibers for efficient CO2 capture.

The excessive CO2 emission has gained global attentions due to its potential effects on climate change, plant nutrition deterioration, and human health and safety. Metal-organic frameworks (MOFs) featured with high specific surface area, adjustable pore size, and tailorable morphology have been widely applied for CO2 capture. However, some drawbacks of poor mechanical stability and uneven distribution of mesopores limit their further applications. Herein, we demonstrate a one-step synthesis of bimetallic center framework (OSSBCF) and pore reconstruction (PRC) strategy to prepare the hierarchical porous Zn/Co-ZIF@ANF aerogels. This unique design achieves the construction of efficient gas transfer channels and creates massive micropores with abundant Lewis basic adsorption sites. Benefiting from theses merits, the bimetallic Zn/Co-ZIF@ANF aerogels demonstrate high MOFs loading mass of 47.51 wt%, high specific surface area of 686.39 m2g-1, and large porosity of 99.31 %. Moreover, the bimetallic Zn/Co-ZIF@ANF aerogels exhibit an enhanced CO2 adsorption capacity of 5.99 mmol/g and CO2/N2 adsorption selectivity of 35 at 25 °C and 1 bar. The CO2 capacity of bimetallic Zn/Co-ZIF@ANF aerogels keep up to 95.19 % after ten cycles of CO2 adsorption, indicating the excellent long-term recycle stability. Therefore, this study provides a promising strategy to engineer hierarchical porous bimetallic MOF aerogels toward practical CO2 capture.

Electrospun radially oriented berberine-PHBV nanofiber dressing patches for accelerating diabetic wound healing.

A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning strategy. The as-electrospun PHBV radially oriented nanofiber dressing patch exhibited uniform and bead-free nanofibrous morphology and innovative radially oriented arrangement, which was demonstrated to possess obviously improved mechanical property, increased surface hydrophilicity and enhanced biological properties compared to the PHBV nanofiber dressing patch control with traditionally randomly oriented pattern. Interestingly, it was found that the radially oriented pattern could induce the cell migration from the periphery to the center along the radially oriented nanofibers in a rapid manner. To further improve the biofunction of PHBV radially oriented nanofiber dressing patch, berberine (Beri, an isoquinoline alkaloid) with two different concentrations were encapsulated into PHBV nanofibers during electrospinning, which were found to present a sustained drug release behavior for nearly one month. Importantly, the addition of Beri could impart the dressing patch with excellent anti-inflammatory property by significantly inhibiting the secretion of pro-inflammatory factors of M1 macrophages, and also showed an additive influence on promoting the proliferation of human dermal fibroblasts (HDFs), as well as inhibiting the growth of E. coli, S. aureus and C. albicans, compared with the Beri-free dressing patch. In the animal studies, the electrospun PHBV radially oriented nanofiber dressing patch loading with high Beri content was found to obviously accelerate the healing process of diabetic mouse full-thickness skin wound with shortened healing time (100% wound closure rate after 18 days' treatment) and improved healing quality (improved collagen deposition, enhanced re-epithelialization and neovascularization and increased hair follicles). In all, this study reported an innovative therapeutic strategy integrating the excellent physical cues of electrospun PHBV radially oriented nanofiber dressing patch with the multiple biological cues of Beri for the effective treatment of hard-to-heal diabetic wounds.

Biodegradable poly(lactic acid) blocked polyurethane/carbon nanotubes coated cotton fabric prepared by ultrasonic-assisted inkjet printing for high performance strain sensors.

In order to fulfill the demands for degradability, a broad working range, and heightened sensitivity in flexible sensors, biodegradable polyurethane (BTPU) was synthesized and combined with CNTs to produce BTPU/CNTs coated cotton fabric using an ultrasonic-assisted inkjet printing process. The synthesized BTPU displayed a capacity for degradation in a phosphate buffered saline solution, resulting in a weight loss of 25 % after 12 weeks of degradation. The BTPU/CNTs coated cotton fabric sensor achieved an extensive strain sensing range of 0-137.5 %, characterized by high linearity and a notable sensitivity (gauge factor (GF) of 126.8). Notably, it demonstrated a low strain detection limit (1 %), rapid response (within 280 ms), and robust durability, enabling precise monitoring of both large and subtle human body movements such as finger, wrist, neck, and knee bending, as well as swallowing. Moreover, the BTPU/CNTs coated cotton fabric exhibited favorable biocompatibility with human epidermis, enabling potential applications as wearable skin-contact sensors. This work provides insight into the development of degradable and high sensing performance sensors suitable for applications in electronic skins and health monitoring devices.

Designing an Innovative Electrospinning Strategy to Generate PHBV Nanofiber Scaffolds with a Radially Oriented Fibrous Pattern.

Electrospinning has contributed substantially to the construction of nanofibrous scaffolds for potential tissue engineering and regenerative medicine applications. However, conventional electrospinning only has the ability to generate and collect nanofiber scaffolds with a randomly oriented fibrous pattern, which lack the necessary cell alignment guidance function. In this study, a novel electrospinning fiber-collecting device was designed and developed by setting a series of small pin-ring-structured collectors on a large plain plate. Specifically, we demonstrated that the pin-ring-structured collectors, which were constructed by inserting a metal pin into the center of a metal ring, could collect the as-electrospun nanofibers with radially oriented structures in an innovative manner. We first investigated the suitable polymeric concentration for electrospinning poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and the optimum electrospinning concentration of PHBV was found to be 12% (w/v) PHBV dissolved in hexafluoroisopropyl alcohol (HFIP). Then, 12% (w/v) PHBV solution was electrospun into radially oriented nanofiber scaffolds using our novel electrospinning strategy, and their various performances were further compared with conventionally randomly oriented nanofiber scaffolds that were also produced from 12% (w/v) PHBV solution. The results showed that the radially oriented PHBV nanofiber scaffolds exhibited obviously enhanced mechanical properties and decreased hydrophobicity compared with the randomly oriented PHBV nanofiber scaffold controls. Importantly, the biological properties of radially oriented PHBV nanofiber scaffolds were also demonstrated to be enhanced, compared with randomly oriented PHBV nanofiber scaffolds, by effectively inducing cell alignment and significantly promoting cell proliferation. In sum, the present study indicates that our as-prepared nanofiber scaffolds with a radially oriented pattern are of great interest for advanced applications, such as wound dressings and tissue-engineered scaffolds.

Recent Advances in Electrospun Nanofiber-Based Strategies for Diabetic Wound Healing Application.

Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.

Design and construction of poly (L-lactic-acid) nanofibrous yarns and threads with controllable structure and performances.

The design and development of electrospun nanofibrous yarns (ENYs) have attracted intensive attentions in the fields of biomedical textiles and tissue engineering, but the inferior fiber arrangement structure, low yarn eveness, and poor tensile properties of currently-obtained ENYs has been troubled for a long time. In this study, a series of innovative strategies which combined a modified electrospinning method with some traditional textile processes like hot stretching, twisting, and plying, were designed and implemented to generate poly (L-lactic-acid) (PLLA) ENYs with adjustable morphology, structure, and tensile properties. PLLA ENYs made from bead-free and uniform PLLA nanofibers were fabricated by our modified electrospinning method, but the as-spun PLLA ENYs exhibited relatively lower fiber alignment degree and tensile properties. A hot stretching technique was explored to process the primary PLLA ENYs to improve the fiber alignment and crystallinity, resulting in a 779.7% increasement for ultimate stress and a 470.4% enhancement for Young's modulus, respectively. Then, the twisting post-treatment was applied to process as-stretched PLLA ENYs, and the tensile performances of as-twisted ENYs was found to present a trend of first increasing and then decreasing with the increasing of twisting degree. Finally, the PLLA threads made from different numbers of as-stretched PLLA ENYs were also manufactured with a traditional plying process, demonstrating the feasibility of further improving the yarn diameter and tensile properties. In all, this study reported a simple and cost-effective technique roadmap which could generate high performance PLLA nanofiber-constructed yarns or threads with controllable structures like highly aligned fiber orientation, twisted structure, and plied structure.

Advances, challenges, and prospects for surgical suture materials.

As one of the long-established and necessary medical devices, surgical sutures play an essentially important role in the closing and healing of damaged tissues and organs postoperatively. The recent advances in multiple disciplines, like materials science, engineering technology, and biomedicine, have facilitated the generation of various innovative surgical sutures with humanization and multi-functionalization. For instance, the application of numerous absorbable materials is assuredly a marvelous progression in terms of surgical sutures. Moreover, some fantastic results from recent laboratory research cannot be ignored either, ranging from the fiber generation to the suture structure, as well as the suture modification, functionalization, and even intellectualization. In this review, the suture materials, including natural or synthetic polymers, absorbable or non-absorbable polymers, and metal materials, were first introduced, and then their advantages and disadvantages were summarized. Then we introduced and discussed various fiber fabrication strategies for the production of surgical sutures. Noticeably, advanced nanofiber generation strategies were highlighted. This review further summarized a wide and diverse variety of suture structures and further discussed their different features. After that, we covered the advanced design and development of surgical sutures with multiple functionalizations, which mainly included surface coating technologies and direct drug-loading technologies. Meanwhile, the review highlighted some smart and intelligent sutures that can monitor the wound status in a real-time manner and provide on-demand therapies accordingly. Furthermore, some representative commercial sutures were also introduced and summarized. At the end of this review, we discussed the challenges and future prospects in the field of surgical sutures in depth. This review aims to provide a meaningful reference and guidance for the future design and fabrication of innovative surgical sutures. STATEMENT OF SIGNIFICANCE: This review article introduces the recent advances of surgical sutures, including material selection, fiber morphology, suture structure and construction, as well as suture modification, functionalization, and even intellectualization. Importantly, some innovative strategies for the construction of multifunctional sutures with predetermined biological properties are highlighted. Moreover, some important commercial suture products are systematically summarized and compared. This review also discusses the challenges and future prospects of advanced sutures in a deep manner. In all, this review is expected to arouse great interest from a broad group of readers in the fields of multifunctional biomaterials and regenerative medicine.

Curcumin Functionalized Electrospun Fibers with Efficient pH Real-Time Monitoring and Antibacterial and Anti-inflammatory Properties.

Wound infection has threatened the health of humans, and developing novel dressings by integrating infection detection and wound treatment in biomaterials is urgently required in the medical industry. In this study, we report a facile strategy to develop curcumin functionalized poly(ε-caprolactone) and gelatin composite fibrous membranes with pH real-time monitoring and antibacterial and anti-inflammatory properties. The developed curcumin-functionalized composite fibers displayed highly sensitive and visible response to the variation of the pH value of a buffer solution in the range of 5.6-8.6. In addition, the resultant fibrous membrane showed obviously enhanced antibacterial efficiency against both E. coli and S. aureus and no obvious cytotoxicity to human dermal fibroblasts when the curcumin content was less than 5 wt %. More importantly, 3 wt % curcumin-functionalized composite membrane exhibited excellent anti-inflammatory activities, good antioxidant activity of ca. 82%, and significantly decreased expression levels of pro-inflammatory cytokines like TNF-α and IL-6 in vitro (p < 0.001). Furthermore, subcutaneous embedding experiments showed that the 3 wt % curcumin-functionalized membrane significantly promoted cell penetration, recruited less macrophages, and facilitated collage deposition. Therefore, the curcumin-functionalized composite fibers could be employed to fabricate multifunctional dressings for the future treatment of chronic wounds.

Tannic acid-crosslinked O-carboxymethyl chitosan hydrogels for enhanced antibacterial activity and rapid hemostasis.

Bacterial infection and massive blood loss are major challenges for global public health. Herein, a series of tannic acid encapsulated O-carboxymethyl chitosan (CMC) based hydrogels were prepared using a facile approach for both hemorrhage control and effective anti-bacterium. The results indicated that the tannic acid-cosslinked CMC hydrogels had excellent mechanical property, swelling ability as well as great cytocompatibility. Comparably, with increasing tannic acid loading, the bleeding control and antibacterial performance against both E. coli and S. aureus were improved simultaneously, especially for the 5% tannic acid-cosslinked CMC hydrogel. Moreover, the prepared CMC hydrogel loading with tannic acid could induce hemocytes and platelets aggregation, promote the blood clotting and achieve bleeding control in vivo due to the interconnected fibrous web structure and the chemical activation (the phenol group of tannic acid). Thus, the resultant CMC hydrogel enabled the maintenance of high bioavailability of tannic acid and synchronization with the interconnected fibrous structure of CMC hydrogels, which was expected to be a promising candidate for robust and safe hemostatic dressings.

Efficacy of preemptive intercostal nerve block on recovery in patients undergoing video-assisted thoracic lobectomy.

BACKGROUND: Preemptive intercostal nerve block (pre-ICNB) achieves the same analgesic effects as postoperative ICNB (post-ICNB) remains unclear. This study aimed to evaluate the efficacy of preemptive ICNB on perioperative outcomes for patients undergoing video-assisted thoracic surgery (VATS). METHODS: This was a randomized, open-label study (ChiCTR2200055667) from August 1, 2021, to December 30, 2021. Eligible patients scheduled for lobectomy for lung cancer were allocated into the pre-ICNB group and the post-ICNB group. The postoperative pain evaluation, patient rehabilitation, and opioid consumption were observed. RESULTS: A total of 81 patients were included. When compared with the post-ICNB group, the pre-ICNB group had a lower proportion of hypertension comorbidity (P = 0.023), significantly lower total consumption of morphine milligram equivalents (MMEs) (P = 0.016), shorter extubation time (P = 0.019). The pre-ICNB group has similar Numeric Rating Scales (NRS) scores of dynamic pain in the post-anesthesia care unit (PACU), postoperative 6 h, 12 h, 24 h, and 48 h (P > 0.05), and had simialr scores of Bruggrmann Comfort Scale (BCS) in postoperative 6 h, 12 h, 24 and 48 h (P > 0.05). The scores of the Mini-mental state examination (MMSE) and Ramsay in the pre-ICNB group were comparable to those in the post-ICNB group, except the scores of MMSE and Ramsay in postoperative 6 h were lower (P = 0.048 and P = 0.019). The pain evaluation in the 1-month follow-up was comparable with that in the post-ICBN group (P > 0.05). CONCLUSIONS: Pre- ICNB is equally efficacious in perioperative pain management as post-ICNB, and pre-ICNB significantly reduces intra-operative opioid consumption, providing faster recovery in PACU. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Register (ChiCTR2200055667).

COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies.

Background: Even 3 years into the COVID-19 pandemic, questions remain about how to safely and effectively vaccinate vulnerable populations. A systematic analysis of the safety and efficacy of the COVID-19 vaccine in at-risk groups has not been conducted to date. Methods: This study involved a comprehensive search of PubMed, EMBASE, and Cochrane Central Controlled Trial Registry data through 12 July 2022. Post-vaccination outcomes included the number of humoral and cellular immune responders in vulnerable and healthy populations, antibody levels in humoral immune responders, and adverse events. Results: A total of 23 articles assessing 32 studies, were included. The levels of IgG (SMD = -1.82, 95% CI [-2.28, -1.35]), IgA (SMD = -0.37, 95% CI [-0.70, -0.03]), IgM (SMD = -0.94, 95% CI [-1.38, -0.51]), neutralizing antibodies (SMD = -1.37, 95% CI [-2.62, -0.11]), and T cells (SMD = -1.98, 95% CI [-3.44, -0.53]) were significantly lower in vulnerable than in healthy populations. The positive detection rates of IgG (OR = 0.05, 95% CI [0.02, 0.14]) and IgA (OR = 0.03, 95% CI [0.01, 0.11]) antibodies and the cellular immune response rates (OR = 0.20, 95% CI [0.09, 0.45]) were also lower in the vulnerable populations. There were no statistically significant differences in fever (OR = 2.53, 95% CI [0.11, 60.86]), chills (OR = 2.03, 95% CI [0.08, 53.85]), myalgia (OR = 10.31, 95% CI [0.56, 191.08]), local pain at the injection site (OR = 17.83, 95% CI [0.32, 989.06]), headache (OR = 53.57, 95% CI [3.21, 892.79]), tenderness (OR = 2.68, 95% CI [0.49, 14.73]), and fatigue (OR = 22.89, 95% CI [0.45, 1164.22]) between the vulnerable and healthy populations. Conclusion: Seroconversion rates after COVID-19 vaccination were generally worse in the vulnerable than healthy populations, but there was no difference in adverse events. Patients with hematological cancers had the lowest IgG antibody levels of all the vulnerable populations, so closer attention to these patients is recommended. Subjects who received the combined vaccine had higher antibody levels than those who received the single vaccine.

Constructing high-strength nano-micro fibrous woven scaffolds with native-like anisotropic structure and immunoregulatory function for tendon repair and regeneration.

Tendon injuries are common debilitating musculoskeletal diseases with high treatment expenditure in sports medicine. The development of tendon-biomimetic scaffolds may be promising for improving the unsatisfactory clinical outcomes of traditional therapies. In this study, we combined an advanced electrospun nanofiber yarn-generating technique with a traditional textile manufacturing strategy to fabricate innovative nano-micro fibrous woven scaffolds with tendon-like anisotropic structure and high-strength mechanical properties for the treatment of large-size tendon injury. Electrospun nanofiber yarns made from pure poly L-lactic acid (PLLA) or silk fibroin (SF)/PLLA blend were fabricated, and their mechanical properties matched and even exceeded those of commercial PLLA microfiber yarns. The PLLA or SF/PLLA nanofiber yarns were then employed as weft yarns interlaced with commercial PLLA microfiber yarns as warp yarns to generate two new types of nanofibrous scaffolds (nmPLLA and nmSF/PLLA) with a plain-weaving structure. Woven scaffolds made from pure PLLA microfiber yarns (both weft and warp directions) (mmPLLA) were used as controls.In vitroexperiments showed that the nmSF/PLLA woven scaffold with aligned fibrous topography significantly promoted cell adhesion, elongation, proliferation, and phenotypic maintenance of tenocytes compared with mmPLLA and nmPLLA woven scaffolds. Moreover, the nmSF/PLLA woven scaffold exhibited the strongest immunoregulatory functions and effectively modulated macrophages towards the M2 phenotype.In vivoexperiments revealed that the nmSF/PLLA woven scaffold notably facilitated Achilles tendon regeneration with improved structure by macroscopic, histological, and ultrastructural observations six months after surgery, compared with the other two groups. More importantly, the regenerated tissue in the nmSF/PLLA group had excellent biomechanical properties comparable to those of the native tendon. Overall, our study provides an innovative biological-free strategy with ready-to-use features, which presents great potential for clinical translation for damaged tendon repair.

Zinc ions and ciprofloxacin-encapsulated chitosan/poly(ɛ-caprolactone) composite nanofibers promote wound healing via enhanced antibacterial and immunomodulatory.

Antibacterial and anti-inflammatory nanofibrous membranes have attracted extensive attention, especially for the cutaneous wound treatment. In this study, zinc ions and ciprofloxacin-encapsulated chitosan/poly(ɛ-caprolactone) (CS/PCL) electrospun core-shell nanofibers were prepared by employing zinc ions-coordinated chitosan as the shell, and ciprofloxacin-functionalized PCL as the core. The morphology and core-shell structure of the as-prepared composite nanofibers were examined by SEM and TEM, respectively. The physical structure and mechanical property of the electrospun membrane were explored by FTIR, swelling, porosity and tensile test. Tensile strength of the zinc ions-coordinated CS/PCL composite nanofibers was enhanced to ca. 16 MPa. Meanwhile, the composite nanofibers can rapidly release of ciprofloxacin during 11 days and effectively suppress above 98 % of S. aureus proliferation. Moreover, the composite nanofibers exhibited excellent guide cell alignment and cyto-activity, as well as significantly down-regulated the inflammation factors, IL-6 and TNF-α in vitro. Animal experiments in vivo showed that the zinc ions-coordinated CS/PCL membrane by means of the synergistic effect of ciprofloxacin and active zinc ions, could significantly alleviate macrophage infiltration, promote collagen deposition and accelerate the healing process of wounds.

Nervous tract-bioinspired multi-nanoyarn model system regulating neural differentiation and its transcriptional architecture at single-cell resolution.

Bioinspired by native nervous tracts, a spinal cord-mimicking model system that was composed of multiple nanofibrous yarns (NYs) ensheathed in a nanofibrous tube was constructed by an innovative electrospinning-based fabrication and integration strategy. The infilling NYs exhibited uniaxially aligned nanofibrous architecture that had a great resemblance to spatially-arranged native nervous tracts, while the outer nanofibrous tubes functioned as an artificial dura matter to provide a stable intraluminal microenvironment. The three-dimensional (3D) NYs were demonstrated to induce alignment, facilitate migration, promote neuronal differentiation, and even phenotypic maturation of seeded neural stem and progenitor cells (NSPCs), while inhibiting gliogenesis. Single-cell transcriptome analysis showed that the NSPC-loaded 3D NY model shared many similarities with native spinal cords, with a great increase in excitatory/inhibitory (EI) neuron ratio. Curcumin, as a model drug, was encapsulated into nanofibers of NYs to exert an antioxidant effect and enhanced axon regeneration. Overall, this study provides a new paradigm for the development of a next-generation in vitro neuronal model system via anatomically accurate nervous tract simulation and constructs a blueprint for the research on NSPC diversification in the biomimetic microenvironment.

Monitoring Prevalence and Persistence of Environmental Contamination by SARS-CoV-2 RNA in a Makeshift Hospital for Asymptomatic and Very Mild COVID-19 Patients.

Objective: To investigate the details of environmental contamination status by SARS-CoV-2 in a makeshift COVID-19 hospital. Methods: Environmental samples were collected from a makeshift hospital. The extent of contamination was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA from various samples. Results: There was a wide range of total collected samples contaminated with SARS-CoV-2 RNA, ranging from 8.47% to 100%. Results revealed that 70.00% of sewage from the bathroom and 48.19% of air samples were positive. The highest rate of contamination was found from the no-touch surfaces (73.07%) and the lowest from frequently touched surfaces (33.40%). The most contaminated objects were the top surfaces of patient cubic partitions (100%). The median Ct values among strongly positive samples were 33.38 (IQR, 31.69-35.07) and 33.24 (IQR, 31.33-34.34) for ORF1ab and N genes, respectively. SARS-CoV-2 relic RNA can be detected on indoor surfaces for up to 20 days. Conclusion: The findings show a higher prevalence and persistence in detecting the presence of SARS-CoV-2 in the makeshift COVID-19 hospital setting. The contamination mode of droplet deposition may be more common than contaminated touches.

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment. Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs. Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new "neural relays" developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion: The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.