Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION: Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Speaking without vocal folds using a machine-learning-assisted wearable sensing-actuation system.

Voice disorders resulting from various pathological vocal fold conditions or postoperative recovery of laryngeal cancer surgeries, are common causes of dysphonia. Here, we present a self-powered wearable sensing-actuation system based on soft magnetoelasticity that enables assisted speaking without relying on the vocal folds. It holds a lightweighted mass of approximately 7.2 g, skin-alike modulus of 7.83 × 105 Pa, stability against skin perspiration, and a maximum stretchability of 164%. The wearable sensing component can effectively capture extrinsic laryngeal muscle movement and convert them into high-fidelity and analyzable electrical signals, which can be translated into speech signals with the assistance of machine learning algorithms with an accuracy of 94.68%. Then, with the wearable actuation component, the speech could be expressed as voice signals while circumventing vocal fold vibration. We expect this approach could facilitate the restoration of normal voice function and significantly enhance the quality of life for patients with dysfunctional vocal folds.

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

PM2.5 Causes Increased Bacterial Invasion by Affecting HBD1 Expression in the Lung.

Our research addresses the critical environmental issue of a fine particulate matter (PM2.5), focusing on its association with the increased infection risks. We explored the influence of PM2.5 on human beta-defensin 1 (HBD1), an essential peptide in mucosal immunity found in the airway epithelium. Using C57BL/6J mice and human bronchial epithelial cells (HBE), we examined the effects of PM2.5 exposure followed by Pseudomonas aeruginosa (P. aeruginosa) infection on HBD1 expression at both mRNA and protein levels. The study revealed that PM2.5's toxicity to epithelial cells and animals varies with time and concentration. Notably, HBE cells exposed to PM2.5 and P. aeruginosa showed increased bacterial invasion and decreased HBD1 expression compared to the cells exposed to P. aeruginosa alone. Similarly, mice studies indicated that combined exposure to PM2.5 and P. aeruginosa significantly reduced survival rates and increased bacterial invasion. These harmful effects, however, were alleviated by administering exogenous HBD1. Furthermore, our findings highlight the activation of MAPK and NF-κB pathways following PM2.5 exposure. Inhibiting these pathways effectively increased HBD1 expression and diminished bacterial invasion. In summary, our study establishes that PM2.5 exposure intensifies P. aeruginosa invasion in both HBE cells and mouse models, primarily by suppressing HBD1 expression. This effect can be counteracted with exogenous HBD1, with the downregulation mechanism involving the MAPK and NF-κB pathways. Our study endeavors to elucidate the pathogenesis of lung infections associated with PM2.5 exposure, providing a novel theoretical basis for the development of prevention and treatment strategies, with substantial clinical significance.

SNR-enhanced signal delivery scheme with delta-sigma modulation in a four-mode fiber system.

This Letter proposes a scheme for optimizing the signal-to-noise ratio (SNR) of signal to improve the system performance by a 1 bit delta-sigma modulation (DSM) in a four-mode MDM system for mobile fronthaul. A 1 bit digitalized signal with an SNR of 60 dB from transmitter digital signal processing (Tx DSP) can be achieved. Based on this system, an experimental demonstration of the ultrahigh-order 1048576-QAM signal transmission over a 50 km strong-coupling few-mode fiber (FMF) is successfully realized. With DSP, the bit error rate (BER) of the received 1048576-QAM signals over four modes transmission is below the 20% soft-decision forward error correction (20% SD-FEC) threshold of 2.4 × 10-2. To the best of our knowledge, this is the first time that the combination of DSM technology and strong-coupling MDM system is achieved and that the highest-modulation order with DSM reported in MDM system is reached. This experimental demonstration of the proposed novel scheme in MDM system can provide an effective solution for ultra-large-capacity mobile fronthaul in the future.

PDM-OFDM 1-bit DSM 1024QAM/4096QAM signals at W-band transmission over 4.6-km wireless distance.

In this Letter, we propose the application of delta-sigma modulation (DSM) higher-order quadrature amplitude modulation (QAM) technology in long-distance transmission of W-band wireless communication, and demonstrate, for the first time to the best of our knowledge, the wireless transmission of millimeter wave signals in the W-band based on 1-bit DSM quantization using polarization-division-multiplexed orthogonal frequency division multiplexing (PDM-OFDM) 1024QAM/4096QAM for 4.6 km. We successfully achieved a bit error rate (BER) of 40-Gbit/s PDM-OFDM 1024QAM and 48-Gbit/s PDM-OFDM 4096QAM after 4.6-km wireless transmission, both lower than the soft decision forward error correction (SD-FEC) of 4.2 × 10-2. To the best of our knowledge, this is the first time that up to 4096QAM signals have been quantized and transmitted based on 1-bit DSM in a 4.6-km-long distance W-band millimeter wave system.

W-band RoF polarization multiplexing system supports 1048576 QAM with delta-sigma modulation.

We propose and experimentally verify a photonics-aided W-band millimeter wave (MMW) radio-over-fiber (RoF) polarization-multiplexed envelope detection system for high-order quadrature amplitude modulation (QAM) signals. To solve the problem of low spectral efficiency of common public radio interface (CPRI) and severe distortion of high-order QAM of envelope detection, quantization noise suppressed delta-sigma modulation (DSM) is introduced into the system. The experimental results show that the system can transmit 131072 QAM signals when meeting the error vector magnitude (EVM) requirements of 5G new radio (NR), and transmit 1048576 QAM signals when meeting the soft decision threshold (SD@20%).

Photonics millimeter wave bidirectional full-duplex communication based on polarization multiplexing.

We have proposed and experimentally implemented a photonics-aided large-capacity long-distance mm-wave bidirectional full-duplex communication system at the W-band based on polarization multiplexing. The same radio frequency (RF) carrier source is shared by both the uplink and the downlink, and a pair of orthomode transducers (OMTs) are used to separate the dual orthogonally polarized channels. To achieve the maximum spectrum efficiency and throughput, 10-Gbaud probabilistically shaped 256-level quadrature-amplitude-modulation (PS-256QAM) signals with 7.07 bit/symbol/Hz are transmitted in Ch. H and Ch. V. The system can support the bidirectional transmission with 103-Gbps data rate over 4600-m RF wireless distance. To the best of our knowledge, based on a photonics-aided bidirectional full-duplex system, this is the first time to realize a record-breaking bit rate-distance product at the W-band, i.e., 103 Gbps × 4.6 km = 473.8 Gbps•km.

A two-way additive model with unknown group-specific interactions applied to gene expression data.

We propose a two-way additive model with group-specific interactions, where the group information is unknown. We treat the group membership as latent information and propose an EM algorithm for estimation. With a single observation matrix and under the situation of diverging row and column numbers, we rigorously establish the estimation consistency and asymptotic normality of our estimator. Extensive simulation studies are conducted to demonstrate the finite sample performance. We apply the model to the triple negative breast cancer (TNBC) gene expression data and provide a new way to classify patients into different subtypes. Our analysis detects the potential genes that may be associated with TNBC.

Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats.

Neural stem cells (NSCs) and derivatives are potential cellular sources to treat neurological diseases. In the current study, we reprogrammed human peripheral blood mononuclear cells into induced NSCs (iNSCs) and inserted GFP gene into the AAVS1 site for graft tracing. Targeted integration of GFP does not affect the proliferation and differentiation capacity of iNSCs. iNSC-GFP can be further differentiated into dopaminergic precursors (DAPs) and motor neuron precursors (MNPs), respectively. iNSCs were engrafted into the motor cortex and iNSC-DAPs into the striatum and substantia nigra (SN) of a nonhuman primate, respectively. The surviving iNSCs could respond to the microenvironment of the cortex and spontaneously differentiate into mature neurons that extended neurites. iNSC-DAPs survived well and matured into DA neurons following transplantation into the striatum and SN. iNSC-MNPs could also survive and turn into motor neurons after being engrafted into the spinal cord of rats. The results suggest that iNSCs and derivatives have a potential to be used for the treatment of neurological diseases.

Association between risk of venous thromboembolism and mortality in patients with COVID-19.

OBJECTIVES: To investigate the association of risk of venous thromboembolism with 30-day mortality in COVID-19 patients. METHODS: A total of 1030 COVID-19 patients were retrospectively collected, with baseline data on demographics, sequential organ failure assessment (SOFA) score, and VTE risk assessment models (RAMs), including Padua prediction score (PPS), International Medical Prevention Registry (IMPROVE), and Caprini. RESULTS: Thirty-day mortality increased progressively from 2% in patients at low VTE risk to 63% in those at high risk defined by PPS. Similar findings were observed in IMPROVE and Caprini scores. Progressive increases in VTE risk were also associated with higher SOFA score. High risk of VTE was independently associated with mortality regardless of adjusted gender, smoking status and some comorbidities, with hazard ratios of 29.19, 37.37 and 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P < 0.001 for all comparisons). The predictive accuracy of PPS (area under curve (AUC) 0.900), IMPROVE (AUC 0.917), or Caprini (AUC 0.861) RAM for risk of hospitalized mortality was unexpectedly strong. CONCLUSIONS: We established that the presence of a high risk of VTE identifies a group of COVID-19 patients at higher risk for mortality. Furthermore, there is a high accuracy of VTE RAMs to predict mortality in these patients.

DVT incidence and risk factors in critically ill patients with COVID-19.

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55-71) years old and 5 (4-6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35-56%). Proximal DVT was recognized in 9% (95% CI 3-15%) of the patients, while 46% (95% CI 35-56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06-0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38-3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03-1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.

High stretchability, strength, and toughness of living cells enabled by hyperelastic vimentin intermediate filaments.

In many developmental and pathological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules (MT), and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules yield or disassemble under moderate strains. Using vimentin containing IFs (VIFs) as a model for studying the large family of IF proteins, we demonstrate that they dominate cytoplasmic mechanics and maintain cell viability at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network in living cells. This network works synergistically with other cytoplasmic components, substantially enhancing the strength, stretchability, resilience, and toughness of cells. Moreover, we find the hyperelastic VIF network, together with other quickly recoverable cytoskeletal components, forms a mechanically robust structure which can mechanically recover after damage.

Culture of pyramidal neural precursors, neural stem cells, and fibroblasts on various biomaterials.

A combinatory approach using biomaterials together with cells may improve the efficacy of cell therapy for treatment of various diseases/indications. In the current study, we cultured pyramidal neural precursors (PNPs), neural stem cells (NSCs), and fibroblasts on different materials that included fibrin, collagen, hyaluronic acid (HA), sciatic nerves, and matrigel, to search for the most suitable biomaterial for culture of each cell type. Collagen was fabricated in both an aligned collagen-poly (lactic-co-glycolic acid) (PLGA) composite and an alveolate form; fibrin and hyaluronic acid were made in an aligned form only. Pyramidal neurons have strong projection ability and have potentials in neural circuit reconstruction. However, PNPs showed difficulty in attaching to and growing neurites on most of the materials tested, except for matrigel, in which neurite growth was observed in a three dimentional culture. NSCs and derivatives hold promise in treating neurological diseases. On aligned fibrin, NSCs could differentiate and grow neurites in a directional manner before fibrin was degraded in 2 days. On aligned collagen-PLGA, induced neural stem cells (iNSCs) could survive and differentiate for at least 2 weeks, but the neurites failed to extend in an aligned way. Fibroblast graft are useful in many indications, such as in skin burns. Fibroblasts generally grew better on the tested materials than did the neural cells, and fibroblasts could grow directionally on the aligned fibrin and scattered around on the alveolate collagen. The study provided information which may be used to further optimize the materials to support culture of each type of cells.

[Endoscopic treatment of small osteoma of nasal sinuses manifested as nasal and facial pain].

OBJECTIVE: To discuss the clinical features, diagnosis and endoscopic surgical intervention for small steoma of nasal sinuses causing nasal and facial pain. METHOD: A retrospective review was performed on 21 patients with nasal and facial pain caused by small osteoma of nasal sinuses, and nasal endoscopic surgery was included in the treatment of all cases. RESULT: The nasal and facial pain of all the patients was relieved. Except for one ase exhibiting periorbital bruise after operation, the other patients showed no postoperative complications. CONCLUSION: Nasal and facial pain caused by small osteoma of nasal sinuses was clinically rare, mostly due to the neuropathic pain of nose and face caused by local compression resulting from the expansion of osteoma. Early diagnosis and operative treatment can significantly relieve nasal and facial pain.