Emerging metallenes: synthesis strategies, biological effects and biomedical applications.

Metallenes, atomically thin-layered materials composed of coordination-deficient metal atoms, have emerged as a new category of two-dimensional materials. Metallenes exhibit exciting properties with a fusion of atom economy, ultrathin structure, photonic properties, and catalytic activity, which make them intriguing for a wide range of applications in biomedicine. The development of biomedical applications of metallenes is in its infancy yet fast-growing. In this review, after a brief introduction of the definition, structures, properties, and classification of metallenes, we outline two common synthesis strategies and identify their shortcomings. Then, we comprehensively discuss the biological effects of metallenes, such as nano-biointeractions and signaling pathway regulation. We also highlight their recent advances in biomedical applications, including antitumor, biosensing, bioimaging, antibacterial, and anti-inflammation. Finally, we provide personal perspectives on remaining challenges and future opportunities for the biomedical applications of metallenes.

MRI-based vertebral bone quality score effectively reflects bone quality in patients with osteoporotic vertebral compressive fractures.

OBJECTIVE: The present study is aimed to validate the ability of the vertebral bone quality (VBQ) score to evaluate bone quality in patients with osteoporotic vertebral compression fractures (OVCF) and to compare it with the ability of T-score by DXA. In addition, the sensitivity of VBQ score with cerebrospinal fluid (CSF) of L2 and L3 segments as baseline is evaluated. METHODS: 196 inpatients were collected and assigned into OVCF and Non-OVCF groups, respectively. For each patient, the VBQ score was calculated by the signal intensity of the L1-L4 vertebral bodies and CSF at L3 or L2 level from T1-weighted MRIs, while T-score from DXA was also obtained. The VBQ and T-score was compared between OVCF and non-OVCF groups, and among age groups. The OVCF ORs by VBQ score and T-score were calculated using logistic regression. RESULTS: OVCF group was significantly different to the non-OVCF group in the T-score (- 2.9 vs. - 0.7) and VBQ score (4.0 vs. 3.5). VBQ score and T-score in patient aged 60-79 years old could indicate the bone quality, but only T-score in patients aged 50-59 years old. OVCF are associated with both higher VBQ score and lower T-score. The VBQ scores calculated by L2 CSF and L3 CSF were similar. CONCLUSIONS: The VBQ score is an effective indicator of bone quality in OVCF patients and comparable to T-score, particularly in people over 60 years old. The VBQ score is not sensitive to CSF of different segments as a baseline.

Disc degeneration contributes to the denser bone in the subendplate but not in the vertebral body in patients with lumbar spinal stenosis or disc herniation.

BACKGROUND CONTEXT: It is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone. PURPOSE: To evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate. STUDY DESIGN/SETTING: A single-center, retrospective cohort study. PATIENT SAMPLE: A total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data. OUTCOME MEASURES: The vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well. METHODS: The age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ. RESULTS: This study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ. CONCLUSIONS: Disc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.

Reprogramming of the transcriptome after heat stress mediates heat hormesis in Caenorhabditis elegans.

Transient stress experiences not only trigger acute stress responses, but can also have long-lasting effects on cellular functions. In Caenorhabditis elegans, a brief exposure to heat shock during early adulthood extends lifespan and improves stress resistance, a phenomenon known as heat hormesis. Here, we investigated the prolonged effect of hormetic heat stress on the transcriptome of worms and found that the canonical heat shock response is followed by a profound transcriptional reprogramming in the post-stress period. This reprogramming relies on the endoribonuclease ENDU-2 but not the heat shock factor 1. ENDU-2 co-localizes with chromatin and interacts with RNA polymerase II, enabling specific regulation of transcription after the stress period. Failure to activate the post-stress response does not affect the resistance of animals to heat shock but eliminates the beneficial effects of hormetic heat stress. In summary, our work discovers that the RNA-binding protein ENDU-2 mediates the long-term impacts of transient heat stress via reprogramming transcriptome after stress exposure.

Anterior Transarticular Crossing Screw Placement for Atlantoaxial Instability in Children: Computed Tomography-Based Study.

OBJECTIVE: The feasibility of anterior transarticular crossing screw (ATCS) fixation for atlantoaxial instability was confirmed in adults. However, atlantoaxial instability is more common in children. Therefore this study was aimed to ascertain the pediatric morphometric characteristics of ATCS in C1-2. METHODS: Morphometric analysis was conducted on computed tomography scan in 87 pediatric patients who were divided into groups based on ages (1-6 years, 7-10 years, and 11-16 years). Measurements were taken in sagittal and axial planes of computed tomography imaging to determine the range of screw lateral angles, incline angles, and screw lengths. RESULTS: The overall screw lengths were relatively longer in males than females. For those aged 1-6 years, the screw lengths were 25.5-32.8 mm in males and 24.2-31.3 mm in females, respectively. The screw lengths showed no difference in the 7- to 10-year group between sexes, while the incline angle was larger in females than males. And the screw lengths were 33.5-43.2 mm in males and 31.2-40.4 mm in females in the 11- to 16-year group. The screw lengths were increased with age, yet the lateral angles were decreased. We also found that the epiphyseal closure of odontoid reached 93.6% when the age was older than 7 years old. Therefore ATCS was recommended for children older than 7 years. CONCLUSIONS: The overall screw lengths and lateral angles of ATCS were larger in male children than those in females, but the incline angles were larger in females. ATCS is feasible in children, particularly those aged 7 years or older.

Ultrathin Hafnium Disulfide Atomic Crystals with ROS-Scavenging and Colon-Targeting Capabilities for Inflammatory Bowel Disease Treatment.

The exciting success of NBTXR3 in the clinic has triggered a tumult of activities in the design and development of hafnium-based nanoparticles. However, due to the concerns of nondegradation and limited functions, the biomedical applications of Hf-based nanoparticles mainly focus on tumors. Herein, tannic acid capped hafnium disulfide (HfS2@TA) nanosheets, a 2D atomic crystal of hafnium-based materials prepared by liquid-phase exfoliation, were explored as high-performance anti-inflammatory nanoagents for the targeted therapy of inflammatory bowel disease (IBD). Benefiting from the transformation of the S2-/S6+ valence state and huge specific surface area, the obtained HfS2@TA nanosheets were not only capable of effectively eliminating reactive oxygen species/reactive nitrogen species and downregulating pro-inflammatory factors but also could be excreted via kidney and hepatointestinal systems. Unexpectedly, HfS2@TA maintained excellent targeting capability to an inflamed colon even in the harsh digestive tract environment, mainly attributed to the electrostatic interactions between negatively charged tannic acid and positively charged inflamed epithelium. Encouragingly, upon oral or intravenous administration, HfS2@TA quickly inhibited inflammation and repaired the intestinal mucosa barrier in both dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid induced IBD models. This work demonstrated that ultrathin HfS2@TA atomic crystals with enhanced colon accumulation were promising for the targeted therapy of IBD.

Anatomical and behavioral outcomes following a graded hemi-contusive cervical spinal cord injury model in mice.

BACKGROUND: A graded hemi-contusion spinal cord injury produces complex anatomical deformation of the spinal cord parenchyma. The relationship between lesion severity and behavioral consequences in a novel contusion mouse model remains unknown. PURPOSE: We aimed to establish a graded cervical hemi-contusion spinal cord injury model in mice and investigate the correlation between graded anatomical damage to the spinal cord and resulting behavioral impairments. METHODS: Thirty-two mice were divided into groups of 1.2 mm, 1.5 mm and sham. The tip of an impactor with a diameter of 1 mm was utilized to compress the left dorsal cord of C5 by 1.2 mm or 1.5 mm at a speed of 300 mm/s. Forelimb motor function was evaluated using rearing, grooming and grip-strength tests before and after the injuries. Histologically the area of white matter sparing, gray matter sparing and lesion area were quantified at 6-week-post-injury. RESULTS: Behavioral assessments showed a more severe forelimb functional deficit in 1.5 mm contusion displacements relative to 1.2 mm contusion displacements after injury. The 1.2 mm hemi-contusion mainly caused damage to the dorsal fasciculus, ventral and dorsal horn, while the 1.5 mm hemi-contusion lead to additional damage extending to ventral fasciculus. Sparing of the gray and white matter at the epicenter was 36.8 ± 2.4% and 12.4 ± 2.6% in the 1.2 mm group, and 27.6 ± 4.0% and 4.1 ± 2.2% in the 1.5 mm group, respectively. Furthermore, the lesion area was 20.8 ± 3.0% and 36.0 ± 2.1% in the 1.2 mm and 1.5 mm groups, respectively. There was a significant correlation between the performance in the grooming test and white matter sparing, and between grip-test strength and gray matter sparing. CONCLUSION: The present study demonstrates that a hemi-contusion cervical spinal cord injury in mice can be graded by contusion displacement and that there is a correlation between anatomical and behavioral outcomes. This study provides a means for determining the severity of lesions in a contusion mouse model.

Modeling and Prediction of Thermophysiological Comfort Properties of a Single Layer Fabric System Using Single Sector Sweating Torso.

Thermophysiological comfort is known to play a primary role in maintaining thermal balance, which corresponds to a person's satisfaction with their immediate thermal environment. Among the existing test methods, sweating torsos are one of the best tools to provide a combined measurement of heat and moisture transfer using non-isothermal conditions. This study presents a preliminary numerical model of a single sector sweating torso to predict the thermophysiological comfort properties of fabric systems. The model has been developed using COMSOL Multiphysics, based on the ISO 18640-1 standard test method and a single layer fabric system used in sportswear. A good agreement was observed between the experimental and numeral results over different exposure phases simulated by the torso test (R2 = 0.72 to 0.99). The model enables a systematic investigation of the effect of fabric properties (thickness, porosity, thermal resistance, and evaporative resistance), environmental conditions (relative humidity, air and radiant temperature, and wind speed), and physiological parameters (sweating rate) to gain an enhanced understanding of the thermophysiological comfort properties of the fabric system.

Cervical Alignment of Patients with Basilar Invagination: A Radiological Study.

OBJECTIVE: To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). METHODS: A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull-C2 /Skull-BV, Skull-C7 , C2 -C7 /BV-C7 wall angles, C0 -C2 /C0 -BV, C0 -C7 , C1 -C7 , and C2 -C7 /BV-C7 angles were measured in dynamic X-ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. RESULTS: The BI patients had a smaller C0 -C2 /C0 -BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2 -C7 /BV-C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2 -C7 /BV-C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = -0.371), extension (r = -0.429), and flexion (r = -0.648) positions among BI patients, as well as in extension position (r = -0.317) among control group. The BI patients presented smaller total ROMs in Skull-C2 /Skull-BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0 -C2 /C0 -BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0 -C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2 -C7 /BV-C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull-C2 /Skull-BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull-C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0 -C2 /C0 -BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull-C2 /Skull-BV (-5.2° ± 9.4° vs -7.3° ± 8.0°), C0 -C2 /C0 -BV (-3.2° ± 8.8° vs -7.7° ± 8.7°), and C0 -C7 angles (-33.2° ± 13.0° vs -52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2 -C7 /BV-C7 wall angle (-33.9° ± 14.8° vs -8.2° ± 15.1°). CONCLUSION: The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.

Neuroprotective Effect of Ketone Metabolism on Inhibiting Inflammatory Response by Regulating Macrophage Polarization After Acute Cervical Spinal Cord Injury in Rats.

OBJECTIVE: To investigate the effects of ketogenic metabolism on macrophage polarization, inflammation inhibition, and function recovery after acute spinal cord injury (SCI) in rats. METHODS: Sixty-four adult male Sprague-Dawley rats were randomly and equally divided into sham, standard diet (SD), ketone diet (KD), and 1, 3-butanediol (BD) groups. All animals underwent C5 unilateral laminectomy, whereas the SD, KD, and BD groups underwent C5 spinal cord hemi-contusion. The impact rod with a diameter of 1.5 mm was aligned 22.5° to the left and 1.4 mm to the midline, and then triggered to deliver a set displacement of 1.5 mm at a speed of 100 mm/s. The gene expression of inflammatory factors as well as the protein expression of inducible nitric oxide synthase, arginase-1, and inflammatory factors were measured at 1 week post-injury. Serum ketone and behavior were evaluated every second week for 12 weeks. Then, histological analyses of the gray and white matter at the epicenter were conducted at 12 weeks post-injury. RESULTS: The serum ketone levels of the KD and BD groups were significantly increased when compared with the SD group. The gene and protein expression of TNF-α and IL-1ß tended to increase after the SCI, but were inhibited in the KD and BD groups. The protein expression of inducible nitric oxide synthase, marker of M1 macrophage, was inhibited in the KD and BD groups; on the other hand, the expression of arginase-1, marker of M2 macrophage, was boosted in the KD and BD groups. The usage of the ipsilateral forelimb was higher in the KD group than in the SD group. The hemi-contusive injury resulted in an obvious ipsilateral lesion area at the epicenter, and there was no significant difference between groups regarding the lesion size. However, the spared gray matter area was significantly greater in the KD group than in the SD and BD groups. CONCLUSION: The present study suggests that ketogenic metabolism promotes macrophage polarization to M2, inhibits an inflammatory response, and alleviates the loss of gray matter after SCI. A higher ketone level, such as that induced by the ketogenic diet, seems to benefit function recovery after SCI.

Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice.

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg-1⋅day-1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate-severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.

A Cervical Spinal Cord Hemi-Contusion Injury Model Based on Displacement Control in Non-Human Primates (Macaca fascicularis).

Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. Twelve adult NHPs were divided into an SCI group (n = 8, 24 and 48 weeks) and a control group (n = 4). An impactor (Φ = 4 mm) was driven to compress the left C5 cord at 800 mm/sec. The contusion displacement and peak force was 4.08 ± 0.17 mm and 19.8 ± 4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68 ± 0.47 mm and 5.99 ± 0.24 mm2 at 24 weeks post-injury (wpi), and 5.29 ± 0.17 mm and 5.95 ± 0.24 mm2 at 48 wpi. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced, while the staining intensity increased at 24 wpi and 48 wpi, compared with the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared with pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the dorsal root ganglia (DRG) was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.

Eco-friendly transparent poplar-based composites that are stable and flexible at high temperature.

Farmed poplar could meet the human demand for transparent wood-based composites to replace glass, avoiding the consumption of natural forest resources. We removed the lignin of poplar using a potassium hydroxide (KOH) and deionized water solution, the waste black liquor could be converted into compound potassium fertilizer after being neutralized by phosphoric acid. Polyurethane (PU) was then added to the lignin-stripped poplar and hardened, the transparent poplar-based composite (TPC) has stable transparency at high temperatures, and flexibility - it elongates (about 15%) before breaking. These properties could provide more uses in hot environments requiring a flexible shape. The TPC PU provides transmittance of 85%, haze of 83%, and anisotropic light diffraction.