Molecular Insights into the Inhibition and Disaggregation Effects of EGCG on Aß40 and Aß42 Cofibrillation.

The misfolding and aggregation of amyloid-ß (Aß) peptides play a pivotal role in the pathogenesis of Alzheimer's disease (AD). Aß40 and Aß42, the two primary isoforms of Aß, can not only self-aggregate into homogeneous aggregates but also coaggregate to form mixed fibrils. Epigallocatechin-3-gallate (EGCG), a prominent tea polyphenol, has shown the capability to prevent the self-aggregation of Aß40 and Aß42 peptides and disaggregate their homogeneous fibrils. However, its effects on the cofibrillation of Aß40 and Aß42 have not yet been explored. Here, we employed molecular dynamic simulations to investigate the effects of EGCG on the coaggregation of Aß40 and Aß42, as well as on their mixed fibril. Our findings indicated that EGCG effectively inhibits the codimerization of Aß40 and Aß42 primarily by impeding the interchain interaction between the two isoforms. The key binding sites for EGCG on Aß40 and Aß42 are the polar residues and aromatic residues, engaging in hydrogen-bond , π-π, and cation-π interactions with EGCG. Additionally, EGCG disaggregates the Aß40-Aß42 mixed fibril by reducing its long-range interaction through similar binding sites and interactions as those between EGCG and Aß40-Aß42 heterodimers. Our research reveals the comprehensive inhibition and disaggregation effects of EGCG on the cofibrillation of Aß isoforms, which provides further support for the development of EGCG as an effective antiaggregation agent for AD.

ACx-projecting cholinergic neurons in the NB influence the BLA ensembles to modulate the discrimination of auditory fear memory.

Animals need discriminating auditory fear memory (DAFM) to survive, but the related neural circuits of DAFM remain largely unknown. Our study shows that DAFM depends on acetylcholine (ACh) signal in the auditory cortex (ACx), which is projected from the nucleus basalis (NB). At the encoding stage, optogenetic inhibition of cholinergic projections of NB-ACx obfuscates distinct tone-responsive neurons of ACx recognizing from fear-paired tone to fear-unpaired tone signals, while simultaneously regulating the neuronal activity and reactivation of basal lateral amygdala (BLA) engram cells at the retrieval stage. This NBACh-ACx-BLA neural circuit for the modulation of DAFM is especially dependent on the nicotinic ACh receptor (nAChR). A nAChR antagonist reduces DAFM and diminishes the increased magnitude of ACx tone-responsive neuronal activity during the encoding stage. Our data suggest a critical role of NBACh-ACx-BLA neural circuit in DAFM: manipulation of the NB cholinergic projection to the ACx via nAChR during the encoding stage affects the activation of ACx tone-responsive neuron clusters and the BLA engram cells during the retrieval stage, thus modulating the DAFM.

Midline Lumbar Fusion Versus Posterior Lumbar Interbody Fusion Involving L5-S1 For Degenerative Lumbar Diseases: A Comparative Study.

BACKGROUND: A retrospective cohort study to evaluate the efficacy and safety of midline lumbar fusion (MIDLF) for lumbosacral fusion compared to posterior lumbar interbody fusion (PLIF). METHODS: Patients who had undergone posterior lumbosacral fusion surgery were divided into a MIDLF group (n = 37) and a PLIF group (n = 42). The follow-up time was at least 12 months. The operation data, recovery condition, complications, clinical outcomes, and status of implants and fusion were compared between the 2 groups. RESULTS: The MIDLF group experienced significantly less blood loss, lower postoperative creatine kinase levels and total drainage volume, earlier time to ambulation, and less hospital stay times after surgery compared to the PLIF group (P < 0.05). The mean postoperative back pain visual analog scale scores in the MIDLF group were significantly lower than the PLIF group (P < 0.05). The improvement in Oswestry Disability Index scores during 3-month follow-up displayed a significant difference between the 2 groups (P < 0.05). The fusion rate tended to be higher in the MIDLF group; however, the difference was not significant (P > 0.05). There was no significant difference in respect to screw loosening and cage subsidence rate. There were 2 cases of complications both occurring in the PLIF group. CONCLUSIONS: MIDLF is safe and effective for lumbosacral fusion and in line with the concept of enhanced recovery after surgery.

A Biomechanical Study on Cortical Bone Trajectory Screw Fixation Augmented With Cement in Osteoporotic Spines.

STUDY DESIGN: A biomechanical study. OBJECTIVE: To evaluate the efficacy and feasibility of cement-augmented cortical bone trajectory (CBT) screw fixation. METHODS: Forty-nine CBT screws were inserted into lumbar vertebrae guided by three-dimensionally printed templates, and then injected with 0, .5, or 1.0 mL of polymethylmethacrylate. The screw placement accuracy, cement dispersion, and cement leakage rate were evaluated radiologically. Biomechanical tests were performed to measure the axial pull-out strength and torque value. RESULTS: Overall, 83.67% of the screws were inserted without pedicle perforation. In the 1.0 mL group, cement dispersed into the pedicle zone and formed a concentrated mass more often than in the .5 mL group, but not significantly more often (P > .05). The total cement leakage rate was 18.75%. Compared with the control group, the torque value was slightly higher in the .5 mL group (P = .735) and significantly higher in the 1.0 mL group (P = .026). However, there was no significant difference between the .5 and 1.0 mL groups (P = .431). The maximal pull-out force (Fmax) was increased by 52.85% and 72.73% in the .5 and 1.0 mL groups, respectively, compared with the control group (P < .05). However, the difference was not significant between the 2 cemented groups (P = .985). CONCLUSIONS: Cement augmentation is a useful method for increasing CBT screw stability in osteoporotic spines. The cement injection volume is recommended to be 1 mL for each screw, and the cement should disperse into the vertebral body than the pedicle zones.

Multi-band orbital angular momentum mode-division multiplexing by a compact set of microstrip ring-shaped resonator antenna.

Optical beams carrying orbital angular momentum (OAM) have received much attention due to the prospects of their use in terahertz communications, biomedical engineering, and imaging. Here we propose an antenna design for the generation of multiple beams carrying OAM with different topological states at the same frequency. The proposed OAM generator is based on a compact set of microstrip ring-shaped resonators. An analytical solution for the radiated field of a single circular ring resonator antenna is derived involving the cavity model and the magnetic current approach. To verify our theoretical description, the numerical full-wave simulation is performed for an actual size OAM generator with the use of the ANSYS HFSS electromagnetic solver, and an antenna prototype operating in the microwave band is fabricated and tested. Conditions of the antenna operation in the combined OAM and mode-division multiplexing (OAM-MDM) regimes are discussed. Obtained results prove that the proposed antenna can be used as a compact and low-cost generator of multiple beams with different OAM states.

Radiological and clinical outcomes of midline lumbar fusion on sagittal lumbar-pelvic parameters for degenerative lumbar diseases.

BACKGROUND: Improving the sagittal lumbar-pelvic parameters after fusion surgery is important for improving clinical outcomes. The impact of midline lumbar fusion (MIDLF) on sagittal lumbar-pelvic alignment for the management of degenerative lumbar diseases is still unknown. AIM: To analyze the effects of short-segment MIDLF and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) on sagittal lumbar-pelvic parameters. METHODS: We retrospectively analyzed 63 patients with degenerative lumbar diseases who underwent single-segment MIDLF or MIS-TLIF. The imaging data of patients were collected before surgery and at the final follow-up. The radiological sagittal parameters included the lumbar lordosis (LL), lower LL, L4 slope (L4S), L5 slope (L5S), L5 incidence (L5I), L1 axis and S1 distance (LASD), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI-LL mismatch (PI-LL). Additionally, the clinical outcomes, including lower back and leg pain visual analog scale (VAS) and Oswestry disability index (ODI) scores, were also analyzed. RESULTS: In both groups, LL and Lower LL significantly increased, while L5I and LASD significantly decreased at the final follow-up compared to that recorded prior to operation (P < 0.05). In the MIDLF group, L4S significantly decreased compared to that recorded prior to operation (P < 0.05), while the mean SS significantly increased and the PT significantly decreased compared to that recorded prior to operation (P < 0.05). In the MIS-TLIF group, SS slightly increased and the mean PT value decreased compared to that recorded prior to operation, but without a statistically significant difference (P > 0.05). However, the PI-LL in both groups was significantly reduced compared to that recorded prior to operation (P < 0.05). There was no significant difference in the sagittal lumbar-pelvic parameters between the two groups prior to operation and at the final follow-up (P > 0.05). In addition, the change in sagittal lumbar-pelvic parameters did not differ significantly, except for ΔLASD within the two groups (P > 0.05). The mean lower back and leg pain VAS and ODI scores in both groups were significantly improved three months after surgery and at the final follow-up. Though the mean ODI score in the MIDLF group three months after surgery was slightly higher than that in the MIS-TLIF group, there was no significant difference between the two groups at the final follow-up. CONCLUSION: Short-segment MIDLF and MIS-TLIF can equally improve sagittal lumbar parameters such as LL, Lower LL, L5I, and LASD in the treatment of lumbar degenerative diseases. However, MIDLF had a larger impact on pelvic parameters than MIS-TLIF.

Directional growth of quasi-2D Cu2O monocrystals on rGO membranes in aqueous environments.

The preparation technology of unconventional low-dimensional Cu2O monocrystals, which exhibit specific crystal planes and present significantly unique interfacial and physicochemical properties, is attracting increasing attention and interest. Herein, by integrating a high-temperature oxidation process under vacuum and a pure-water incubation process under ambient conditions, we propose the self-assembled growth and synthesis of quasi-two-dimensional Cu2O monocrystals on reduced graphene oxide (rGO) membranes. The prepared Cu2O crystals have a single (110) crystal plane, regular rectangular morphology, and potentially well conductivity. Experimental and theoretical results suggest that this assembly is attributed to the pre-nucleation clusters aggregation and directional attachment of Cu and O on the rGO membranes in aqueous environment and cation-π interactions between the (110) crystal plane of Cu2O and rGO surface. Our findings offer a potential avenue for the discovery and design of advanced low-dimensional single-crystal materials with specific interfacial properties in a pure aqueous environment.

Thoracolumbar surgery for degenerative spine diseases complicated with tethered cord syndrome: A case report.

BACKGROUND: Tethered cord syndrome (TCS) secondary to split cord malformation (SCM) is rare in adulthood. There is as yet no consensus about the optimal treatment method for adult patients with SCMs and degenerative spine diseases such as lumbar stenosis, spondylolisthesis and ossification of the ligamentum flavum (OLF). The tethered cord poses a great challenge to the decompression and fusion procedures for the intraoperative stretching of the spinal cord, which might lead to deteriorated neural deficits. Here, we report on a case to add our treatment experience to the medical literature. CASE SUMMARY: We treated a 67-year-old female patient with type II SCM suffering from lumbar disc herniation, degenerative lumbar spondylolisthesis and thoracic OLF. The patient underwent thoracolumbar spinal fusion and decompression surgery for severe lower back pain, extensive left lower limb muscle weakness and intermittent claudication. After the thoracolumbar surgery, without stretching the tethered cord, the patient achieved complete relief of pain and lower extremity weakness at final follow-up. CONCLUSION: For adult patients with underlying TCS secondary to SCM coupled with thoracic OLF and lumbar spondylolisthesis, a thoracolumbar fusion surgery could be safe and effective with the tethered cord untreated. It is critical to design individualized surgical protocols to reduce the stretch of the low-lying spinal cord.

A Novel Calcium Phosphate-Based Nanocomposite for Augmentation of Cortical Bone Trajectory Screw Fixation.

Purpose: To evaluate the effect of cement augmentation of cortical bone trajectory (CBT) screws using a novel calcium phosphate-based nanocomposite (CPN). Material and Methods: CBT screws were placed into cadaveric lumbar vertebrae. Depending on the material used for augmentation, they were divided into the following three groups: CPN, polymethylmethacrylate (PMMA), and control. Radiological imaging was used to evaluate the cement dispersion. Biomechanical tests were conducted to measure the stability of CBT screws. A rat cranial defect model was used to evaluate biodegradation and osseointegration of the CPN. Results: After cement augmentation, the CPN tended to disperse into the distal part of the screws, whereas PMMA remained limited to the proximal part of the screws (P < 0.05). As for cement morphology, the CPN tended to form a concentrated mass, whereas PMMA arranged itself as a scattered cement cloud, but the difference was not significant (P > 0.05). The axial pullout test showed that the average maximal pullout force (Fmax) of CPN-augmented CBT screws was similar to that of the PMMA group (CPN, 1639.56 ± 358.21 N vs PMMA, 1778.45 ± 399.83 N; P = 0.745) and was significantly greater than that of the control group (1019.01 ± 371.98 N; P < 0.05). The average torque value in the CPN group was higher than that in the control group (CPN, 1.51 ± 0.78 N∙m vs control, 0.97 ± 0.58 N∙m) and lower than that in the PMMA group (1.93 ± 0.81 N∙m), but there were no statistically significant differences (P > 0.05). The CPN could be biodegraded and gradually replaced by newly formed bone tissue after 12 weeks in a rat cranial defect model. Conclusion: The biocompatible CPN could be a valuable augmentation material to enhance CBT screw stability.

Heat Shock-Induced Accumulation of the Glycogen Synthase Kinase 3-Like Kinase BRASSINOSTEROID INSENSITIVE 2 Promotes Early Flowering but Reduces Thermotolerance in Arabidopsis.

Brassinosteroids (BRs) are essential plant growth- and development-regulating phytohormones. When applied exogenously, BRs ameliorate heat shock (HS)-induced cell damage and enhance plant thermotolerance; however, the molecular mechanism by which BRs regulate plant thermotolerance is unknown. In this study, by analyzing the thermotolerance of a series of BR signaling mutants and plants that overexpressed different BR signaling components, we obtained comprehensive data showing that BRASSINOSTEROID INSENSITIVE 2 (BIN2) plays a major role in mediating the crosstalk between BR signaling and plant HS responses. By RNA-Seq, 608 HS- and BIN2-regulated genes were identified. An analysis of the 1-kb promoter sequences of these genes showed enrichment of an abscisic acid (ABA) INSENSITIVE 5 (ABI5)-binding cis-element. Physiological studies showed that thermotolerance was reduced in bin2-1 mutant and ABI5-OX plants but increased in the abi5 mutant, and that the abi5 mutation could recover the thermotolerance of bin2-1 plants to a wild-type level, suggesting that ABI5 functions downstream of BIN2 in regulating plant thermotolerance. Further, HS treatment increased the cellular abundance of BIN2. Both bin2-1 mutant and BIN2-OX plants showed early flowering, while the BIN2 loss-of-function mutant bin2-3 bil1 bil2 flowered late. Given these findings, we propose that under HS conditions plants increase BIN2 activity to promote early flowering and ensure species survival; however, this reduces the thermotolerance and survivability of individual plants partially by activating ABI5.

The Biomechanical Properties of Cement-Augmented Pedicle Screws for Osteoporotic Spines.

STUDY DESIGN: This is a broad, narrative review of the literature. OBJECTIVE: In this review, we describe recent biomechanics studies on cement-augmented pedicle screws for osteoporotic spines to determine which factors influence the effect of cement augmentation. METHODS: A search of Medline was performed, combining the search terms "pedicle screw" and ("augmentation" OR "cement"). Articles published in the past 5 years dealing with biomechanical testing were included. RESULTS: Several factors have been identified to impact the effect of cement augmentation in osteoporotic spines. These include the type of augmentation material, the volume of injected cement, the timing of augmentation, the severity of osteoporosis, the design of the pedicle screw, and the specific augmenting technique, among others. CONCLUSIONS: This review elaborates the biomechanics of cement-augmented pedicle screws, determines which factors influence the augmentation effect, and identifies the risk factors of cement leakage in osteoporotic bone, which might offer some guidance when using this technique in clinical practice. Further, we provide information about newly designed screws and recently developed augmentation materials that provide higher screw stability as well as fewer cement-related complications.

Investigation and source analysis of bacterial contamination in groundwater in Liuzhou City, China.

Groundwater is an important water source to consider when ensuring the safety of urban water supply. Groundwater contaminated by bacteria poses a potential health risk to the drinking water supply. This study focuses on the water supply of Liuzhou City, a famous industrial city in China. Analyses of the concentrations, spatial distribution, and pollution sources of bacteria in the groundwater were conducted based on samples collected from 27 wells during the wet and dry seasons in 2018. The total colony counts and total coliform were high during both the wet and dry seasons, posing a severe threat to the emergency water supply security for more than one million people in the city. The groundwater in Liuzhou City is generally contaminated by bacteria, with higher pollution levels in the northern urban-rural fringe and central urban areas. Domestic pollution is the main sources of groundwater bacteria. In addition, bacterially contaminated rivers (Liujiang River) passing through the urban area likely transfer bacteria to the groundwater due to the circulation of the groundwater and surface river water. Controlling the bacterial pollution of groundwater in this region requires adherence to a long-term management plan.

Environmental geochemical maps of harmful trace elements in Chinese coalfields.

Coal resource utilization and environmental protection is a critical global issue. This study aims to address the need for geochemical maps of harmful trace elements (HTEs) in Chinese coalfields and to extract scientific information from these maps. Based on data extracted from the Trace Elements in Coal of China database, geochemical maps of As, Cd, Cr, F, Hg, Ni, Pb, and Se in Chinese coalfields were generated, for the first time, using the ArcGIS platform. Differences in regional HTE concentrations were attributed to multiple factors, including the type of coal-forming environment, terrigenous debris, and groundwater effect. However, on a national scale, the spatial distribution pattern of HTEs in coal is affected by the abundance of elements in the earth's crust. Herein, the enrichment anomaly of HTEs in coal were found to be significantly correlated with fault locations, and hydrothermal fluid action was characterized as the primary causal factor. HTE abundance in coal is the result of geochemical cycles in the earth's crust. Additionally, stratum fracture zones may serve as conduits and material sources for the migration of HTEs from deep layers to shallow layers, including coal seams. This study provides an essential reference for extensive map applications and coal environmental management while advancing our understanding of the spatial distribution patterns of chemical elements in coal.

Spatial distribution of harmful trace elements in Chinese coalfields: An application of WebGIS technology.

Harmful trace elements in coal have caused serious damage to the environment and human health. Understanding their spatial distribution is helpful for environmental health assessment and for their effective control and utilization. To further explore the geospatial distribution of harmful trace elements found in Chinese coals, this work constructed the Trace Elements in Chinese Coals Database Management System (TECC), and analysed the spatial distribution of harmful trace elements by applying spatial data algorithms and visual technology of WebGIS. The main results are as follows: (1) The mean concentrations of 25 harmful trace elements (Ag, As, B, Ba, Be, Cd, Cl, Co, Cr, Cu, F, Hg, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Th, Tl, U, V, Zn) in Chinese coals are provided, using the "reserve-concentration" weighted calculation method; (2) Using As, Hg, F, and U as examples, the spatial distribution of harmful trace elements in Chinese coalfields is visually displayed; (3) Harmful trace elements are extremely unevenly distributed in Chinese coalfields; they are mainly concentrated in south China, especially in the southwest region, and some elements may also be concentrated in coals from northwest, northeast, and north China. The enrichment of harmful trace elements in Chinese coals is the result of a combination of multiple factors, such as the nature of the region the coal is sourced from, sedimentary facies, coal-forming plants, and magmatic hydrothermal processes. This work can serve as a reference for the study of harmful trace elements in coal, including assessment of their environmental and health impacts.

[Preliminary study on transgenic cell sheet with cartilage-derived morphogenetic protein].

OBJECTIVE: To construct a transgenic cell sheet of cartilage-derived morphogenetic protein 1 (CDMP1) by adenovirus vector in vitro and to identify its biological activity. METHODS: The bone mesenchymal stem cells (BMSCs) were isolated from bone marrow of 1-month-old rabbit, and cultured in vitro. The 3rd-6th generation of BMSCs were used for experiment. The experiment was divided into 3 groups: BMSCs transfected by adenovirus (Ad)-cytomegalovirus (CMV)-human CDMP1 (hCDMP1)-internal ribosome entry site (IRES)-enhanced green fluorescent protein (EGFP) in group A, BMSCs transfected by Ad-CMV-EGFP in group B, and untransfected BMSCs in group C. The expression of green fluorescence was observed in 3 groups under fluorescent inverted microscope. MTT assay was used to detect the proliferation of the cells. The cell sheet was obtained by means of temperature-responsive culture dish for 14 days. The morphological and HE staining observations of the cell sheet were carried out. RT-PCR and Western blot were used to detect the expressions of hCDMP1 and collagen type II at gene and protein levels, while alcian blue staining was used to detect the expression of glycosaminoglycans (GAG). RESULTS: Bright green fluorescence was observed in transfected cells at 72 hours under fluorescent inverted microscope, and the transfection efficiency was up to 90%. MTT assay showed approximate S-shaped growth curves in 3 groups, showing no significant difference in the absorbance (A) value among 3 groups within 9 days (P > 0.05). The three-dimensional cell sheets were successfully harvested in vitro. The RT-PCR and Western blot showed that there were positive expressions of hCDMPl and collagen type II in group A and negative expression in other 2 groups. HE staining and alcian blue staining showed that there were rich fibrous tissues, mass extracellular matrix, and dark blue metachromatic granules in group A, but there was less fibrous tissues and no specific blue metachromatic granules in other 2 groups; and the positive expression area was significantly lower and gray scale of GAG was significantly higher in group A than that in groups B and C (P < 0.05). CONCLUSION: A transgenic cell sheet of exogenous recombinant hCDMP1 by adenovirus vector can express collagen type II and GAG, so it has chondrogenic capacity. This technology that overcomes limitations in traditional tissue engineering, such as low cell-attachment efficiency and inflammatory reaction, may be a new tissue engineering approach for hard tissue reconstruction and is hopeful to build a large density of tissue engineered cartilage.