Spinal column radiological factors associated with increased spinal cord intramedullary signal intensity - A study evaluating aging spinal cord's relation to spinal disc degeneration.

PURPOSE: Increased intramedullary signal intensity (IISI) on T2 weighted MRI scan (T2WI) can be a radiological feature of spinal cord degeneration. However, the association of IISI to degeneration of the spinal column that protects the spinal cord remains unclear. The purpose of this study was to determine the prevalence of IISI and analyze the independent relationship between IISI and cervical degenerative parameters on X-ray and magnetic resonance imaging (MRI). METHODS: A retrospective review of MRI, X-ray, and radiology data (n = 144) adult patients with both cervical MRI and X-ray scans was conducted. A total of 39 (27 %) patients with IISI was identified. The remaining 105 patients without IISI made up the control group. RESULTS: IISI was most frequent in C6-C7 cervical levels. The likelihood of having IISI was 1.947 (Exp(B) 1.947, 95 %CI [1.004-3.776]) times higher in segmental levels with facet joint degeneration. There was an increased likelihood of IISI within the spinal cord with increasing age (Exp(B) 1.034, 95 %CI [1.008-1.060]), maximum spinal cord compression (MSCC) (Exp(B) 1.038, 95 %CI [1.003-1.075]), rotational angle (Exp(B) 1.082, 95 %CI [1.020-1.148]) and posterior disc herniation width (Exp(B) 1.333, 95 %CI [1.017-1.747]) and decreasing Torg-Pavlov ratio (Exp(B) 0.010, 95 %CI [0.001-0.068]). CONCLUSION: IISI was independently associated with increased age, facet joint degeneration, MSCC, rotational angle, posterior herniation width and decreasing Torg-Pavlov angle. Radiologicaldegenerative changesassociated with IISI indicates a potential for identifying predictors of age related spinal cord morphological changes in DCM, which may allow for early intervention strategies in the future.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

3.05 kW, 13.7 GHz linewidth fiber amplifier based on PRBS phase modulation for SBS suppression.

In this paper, we establish a multi-stage fiber amplifier with pseudo-random binary sequence (PRBS) phase modulation. The stimulated Brillouin gain spectra of the main amplifier with both the unmodulated and pseudo-random binary sequence phase modulated configuration are measured (with corresponding output power), and the stimulated Brillouin scattering (SBS) threshold is investigated experimentally and theoretically. The pseudo-random binary sequence phase modulation parameters are optimized by theoretical simulation. With a two-stage preamplifier chain and a counter-pumping main amplifier stage, a maximum 3.05 kW output power with a slope efficiency of 85.9% is obtained experimentally. The central wavelength of the fiber amplifier is 1050 nm, associated with a full-width at half-maximum linewidth of 13.7 GHz. The stimulated Brillouin scattering reflectivity is below 0.01% at 3.05 kW at 13.7 GHz, which indicates that stimulated Brillouin scattering can be suppressed efficiently at this power and linewidth level.

Nanoparticles targeting the adenosine pathway for cancer immunotherapy.

Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.

The Role of Pelvic Compensation in Sagittal Balance and Imbalance: The Impact of Pelvic Compensation on Spinal Alignment and Clinical Outcomes Following Adult Spinal Deformity Surgery.

BACKGROUND AND OBJECTIVES: The Scoliosis Research Society (SRS)-Schwab system does not include a pelvic compensation (PC) subtype, potentially contributing to gaps in clinical characteristics and treatment strategy for deformity correction. It also remains uncertain as to whether PC has differing roles in sagittal balance (SB) or imbalance (SI) status. To compare radiological parameters and SRS-22r domains between patients with failed pelvic compensation (FPC) and successful pelvic compensation (SPC) based on preoperative SB and SI. METHODS: A total of 145 adult spinal deformity patients who received deformity correction were analyzed. Radiographic and clinical outcomes were collected for statistical analysis. Patients were classified into 4 groups based on the median value of PT/PI ratio (PTr) and the cutoff value of SB. Patients with low PTr and high PTr were defined as FPC and SPC, respectively. Radiographic and clinical characteristics of different groups were compared. RESULTS: Patients with SPC exhibited significantly greater improvements in lumbar lordosis, pelvic tilt, PTr, and T1 pelvic angle as compared to patients with FPC, irrespective of SB or SI. No apparent differences in any of SRS-22r domains were observed at follow-up when comparing the SB-FPC and SB-SPC patients. However, patients with SI-SPC exhibited significantly better function, self-image, satisfaction, and subtotal domains at follow-up relative to those with SI-FPC. When SI-FPC and SI-SPC patients were subdivided further based on the degree of PI-LL by adjusting for age, the postoperative function and self-image domains were significantly better in the group with overcorrection of PI-LL than undercorrection of PI-LL in SI-FPC patients. However, no differences in these SRS-22r scores were observed when comparing the subgroups in SI-SPC patients. CONCLUSION: Flexible pelvic rotation is associated with benefits to the correction of sagittal parameters, irrespective of preoperative SB or SI status. However, PC is only significantly associated with clinical outcomes under SI. Patients with SI-FPC exhibit poorer postoperative clinical outcomes, which should be recommended to minimize PI-LL.

Non-equilibrium compression achieving high sensitivity and linearity for iontronic pressure sensors.

Flexible pressure sensors with high sensitivity and linearity are highly desirable for robot sensing and human physiological signal detection. However, the current strategies for stabilizing axial microstructures (e.g., micro-pyramids) are mainly susceptible to structural stiffening during compression, thereby limiting the realization of high sensitivity and linearity. Here, we report a bending-induced non-equilibrium compression process that effectively enhances the compressibility of microstructures, thereby crucially improving the efficiency of interfacial area growth of electric double layer (EDL). Based on this principle, we fabricate an iontronic flexible pressure sensor with vertical graphene (VG) array electrodes. Ultra-high sensitivity (185.09 kPa-1) and linearity (R2 = 0.9999) are realized over a wide pressure range (0.49 Pa-66.67 kPa). It also exhibits remarkable mechanical stability during compression and bending. The sensor is successfully employed in a robotic gripping task to recognize the targets of different materials and shapes based on a multilayer perception (MLP) neural network. It opens the door to realizing haptic sensing capabilities for robotic hands and prosthetic limbs.

Identifying the miRNA-gene networks contributes to exploring paravertebral muscle degeneration's underlying pathogenesis and therapy strategy.

Low back pain (LBP) is a worldwide problem with public health. Paravertebral muscle degeneration (PMD) is believed to be associated with LBP. Increasing evidence has demonstrated that microRNA (miRNA)-mRNA signaling networks have been implicated in the pathophysiology of diseases. Research suggests that cell death, oxidative stress, inflammatory and immune response, and extracellular matrix (ECM) metabolism are the pathogenesis of PMD; however, the miRNA-mRNA mediated the pathological process of PMD remains elusive. RNA sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) are invaluable tools for uncovering the functional biology underlying these miRNA and gene expression changes. Using scRNA-seq, we show that multiple immunocytes are presented during PMD, revealing that they may have been implicated with PMD. Additionally, using RNA-seq, we identified 76 differentially expressed genes (DEGs) and 106 differentially expressed miRNAs (DEMs), among which IL-24 and CCDC63 were the top upregulated and downregulated genes in PMD. Comprehensive bioinformatics analyses, including Venn diagrams, differential expression, functional enrichment, and protein-protein interaction analysis, were then conducted to identify six ferroptosis-related DEGs, two oxidative stress-related DEGs, eleven immunity-related DEGs, five ECM-related DEGs, among which AKR1C2/AKR1C3/SIRT1/ALB/IL-24 belong to inflammatory genes. Furthermore, 67 DEMs were predicted to be upstream miRNAs of 25 key DEGs by merging RNA-seq, TargetScan, and mirDIP databases. Finally, a miRNA-gene network was constructed using Cytoscape software and an alluvial plot. ROC curve analysis unveiled multiple key DEGs with the high clinical diagnostic value, providing novel approaches for diagnosing and treating PMD diseases.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering.

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Incremental Load Respiratory Muscle Training Improves Respiratory Muscle Strength and Pulmonary Function in Children with Bronchiectasis.

Methods: Participants underwent respiratory muscle training for 24 weeks. The main results were changes in respiratory muscle strength and pulmonary function indices (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), forced expiratory flow 25-75% (FEF25-75%), and maximal midexpiratory flow 75/25 (MMEF75/25)) before, 12 weeks after, and 24 weeks after the intervention. The secondary outcomes were changes in the exercise load and work rate, exercise work, Leicester Cough Questionnaire (LCQ) scale, and Fatigue Severity Scale (FSS). Results: Compared with before the intervention, after 24 weeks of respiratory muscle training, the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were significantly enhanced (P < 0.05), while FVC, FEV1, and PEF were significantly increased (P < 0.01). FEF25-75 and MMEF75/25 values showed significant improvement compared to those before training (P < 0.05). The exercise loading, work, and exercise work rate of expiratory muscle training were significantly improved compared to those before intervention (P < 0.05). The LCQ score increased significantly (P < 0.001), and the FSS score decreased significantly (P < 0.001). Conclusion: Incremental load respiratory muscle training effectively improved children's lung function over the long term, improved the strength of their inspiratory and expiratory muscles, and improved their quality of life.

Developmental origins shape the paediatric cancer genome.

In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.

Metabolic Modulation-Mediated Antibiotic and Immune Activation for Treatment of Chronic Lung Infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Path to pollution and carbon reduction synergy from the perspective of the digital economy: Fresh evidence from 292 prefecture-level cities in China.

The digital economy is a crucial focus for realizing the transformation of old and new kinetic energy in China. It is widely integrated with various fields of the economy and society, constantly providing a new dynamic mechanism with synergetic control of environmental pollution and carbon emissions (SCEPCE). Based on panel data from 292 prefecture-level cities in China from 2011 to 2021, this study discusses the spatial effects and mechanisms of the digital economy on the coordinated control of pollutants and carbon emissions. The study found that: (1) The digital economy has direct and indirect influences on the coordinated control of pollutants and carbon emissions. The digital economy can drive reductions in pollutants and carbon dioxide emissions by upgrading industrial structures and transforming energy structures. (2) Green innovation plays an active regulatory role in the digital economy and structural optimization, particularly in the context of SCEPCE. This interference helps mitigate the impact of the digital economy on pollution and carbon emissions. (3) The digital economy has a significant spatial spillover effect on the coordinated control of pollutants and carbon emissions. (4) The influence mechanism of the digital economy on pollution reduction and carbon reduction synergy exhibits geographical heterogeneity, resource endowment heterogeneity. To enhance the synergy of pollution reduction and carbon reduction, it is essential to bolster support and optimise the digital economy at various levels. This includes reinforcing regional balance, considering spatial spillover effects, and enhancing the leading role of developed cities in the region.

Chronic kidney disease with malignant peripheral nerve sheath tumor of the ureter: a case report.

Malignant peripheral nerve sheath tumors (MPNSTs) are a complex group of malignant tumors originating from nerve cells or benign peripheral nerve sheath tumors and are commonly found in major plexus/nerve root sites such as the limbs, head, and neck. Malignant peripheral nerve sheath tumors originating in the ureter are extremely rare. Herein, we report the case of a 63-year-old patient with a malignant peripheral nerve sheath tumor of the right ureter who underwent laparoscopic radical resection of the right kidney and ureter. The patient also had stage 5 chronic kidney disease (CKD). Therefore, chemotherapy and radiotherapy were not considered. No tumor recurrence was observed during the follow-up period.

MicroRNAs regulate the vicious cycle of vascular calcification-osteoporosis in postmenopausal women.

Menopause is a normal physiological process accompanied by changes in various physiological states. The incidence of vascular calcification (VC) increases each year after menopause and is closely related to osteoporosis (OP). Although many studies have investigated the links between VC and OP, the interaction mechanism of the two under conditions of estrogen loss remains unclear. MicroRNAs (miRNAs), which are involved in epigenetic modification, play a critical role in estrogen-mediated mineralization. In the past several decades, miRNAs have been identified as biomarkers or therapeutic targets in diseases. Thus, we hypothesize that these small molecules can provide new diagnostic and therapeutic approaches. In this review, we summarize the close interactions between VC and OP and the role of miRNAs in their interplay.

Impacts of different slash disposals on soil and water erosion of high-intensity management Eucalyptus grandis × urophylla plantation.

Background: The slash disposal-burning forest-in high-intensity management Eucalyptus grandis × urophylla plantation has accelerated soil degradation. Statement of the problem: Slash disposals is a contributing factor, but its specific role in the correlation between rainfall-runoff and soil erosion remains elusive. Objectives: his study investigated the characteristics of rainfall-runoff and soil erosion resistance in different methods of slash disposals in plantation. Methods: Three methods of slash disposal, namely burning forest (BF), moving away (MA), and spreading evenly (SE), were established. A field simulation experiment of rainfall was conducted, and path analysis was used. Results: The findings revealed that the water holding, infiltrating properties and the time the rainfall-runoff generated of SE were increased by approximately 10∼20 %, 100 %, and 80 %, respectively, compared with BF and MA. Water loss, soil loss and nutrient loss were significantly reduced by 62.23 % and 61.56 %, 69.06 % and 49.55 %, and 58.8 % and 65.42 % in SE and BF compared to MA. Path analysis suggested that different from BF and MA, the correlation between soil water properties and rainfall-runoff factors in SE was weakened, simultaneously considering the result that SE had the lower proportions of silt for sediment component (75.31 %), it stabilized the soil structure. Conclusions and prospect: Consequently, SE mitigated the erosion force by reducing rainfall-runoff and enhancing the anti-erosion of soil through improved water properties, making it a viable slash disposal. This work provides a detailed description of the soil erosion characteristics of plantation, including water, soil, and nutrient losses caused by rainfall-runoff, as well as the soil anti-erosion due to different slash disposals. These findings offer valuable insights for the management of high-intensity Eucalyptus grandis × urophylla plantations.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

Metabolic Engineering of Corynebacterium glutamicum for Highly Efficient Production of Ectoine.

Ectoine is a compatible solute that functions as a cell protector from various stresses, protecting cells and stabilizing biomolecules, and is widely used in medicine, cosmetics, and biotechnology. Microbial fermentation has been widely used for the large-scale production of ectoine, and a number of fermentation strategies have been developed to increase the ectoine yield, reduce production costs, and simplify the production process. Here, Corynebacterium glutamicum was engineered for ectoine production by heterologous expression of the ectoine biosynthesis operon ectBAC gene from Halomonas elongata, and a series of genetic modifications were implemented. This included introducing the de3 gene from Escherichia coli BL21 (DE3) to express the T7 promoter, eliminating the lysine transporter protein lysE to limit lysine production, and performing a targeted mutation lysCS301Y on aspartate kinase to alleviate feedback inhibition of lysine. The new engineered strain Ect10 obtained an ectoine titer of 115.87 g/L in an optimized fed-batch fermentation, representing the highest ectoine production level in C. glutamicum and achieving the efficient production of ectoine in a low-salt environment.

JNK signaling mediates acute rejection via activating autophagy of CD8+ T cells after liver transplantation in rats.

Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear. Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored. Results: The expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex. Conclusion: JNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.