LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes.

Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the interaction of lincRNA-p21/AIF-1/CMPK2/NLRP3 via exosomes in urate nephropathy. This study evaluated the effect of lincRNA-p21/AIF-1/CMPK2/NLRP3 using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. In clinical research section, the level of lincRNA-p21/AIF-1 in exosomes of urine in patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the level of exosomes, inflammation, autophagy, and apoptosis was increased in HK2 cells induced by urate. Additionally, the expression of lincRNA-p21, AIF-1, CMPK2, and NLRP3 was upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors regulated the level of inflammation, autophagy, and apoptosis in HK2 cells. In conclusion, the pathway of lincRNA-p21/AIF-1/CMPK2/NLRP3 contributed to inflammation, autophagy, and apoptosis of human renal tubular epithelial cell induced by urate via exosomes. Additionally, the specific exosomes in urine might serve as novel biomarkers for urate nephropathy.

Assessment of joint position sense in active and passive modes with various elbow flexion angles and movement speeds using an isokinetic dynamometer.

BACKGROUND: Joint position sense is the ability to detect body segment position in space and is commonly used to represent proprioceptive performance. The isokinetic dynamometer is frequently used to evaluate elbow joint position sense during active and passive reproduction tasks with various testing protocols. However, few studies have reported the performance of joint position sense under different testing conditions. OBJECTIVE: To compare elbow joint position sense between active and passive reproduction tasks under different matching speeds and reference targets. DESIGN: A cross-sectional study. METHODS: Twenty participants without a history of upper-extremity surgery or neuromuscular diseases that affect the joint position sense of the elbow. Active and passive ipsilateral matching tasks were performed at four movement speeds (0.5°/s, 1°/s, 2°/s, and 4°/s) and three reference targets (elbow flexion at 0°-15°, 45°-60°, and 75°-90°), using an isokinetic dynamometer. The absolute and variable errors of each condition were calculated for comparison. RESULTS: In active matching task with elbow flexion of 0°-15°, the absolute error at 0.5°/s was significantly larger than that at 2°/s and 4°/s, while the variable error at 1°/s was significantly larger than that at 2°/s. However, no differences were found at elbow flexion angles of 45°-60° and 75°-90°. Larger absolute errors were found at 4°/s with three testing angles in passive matching task. CONCLUSIONS: This study compared the joint position sense errors under various testing conditions in the active and passive reproduction tasks. The movement speeds and target position effects should be considered during evaluation.

Mutual synergistic regulation of chloride anion and cesium cation binding using a new designed macrocyclic multi-functional sites receptor: A case of DFT computational prediction.

The mutual synergistic regulation of the multi-functional sites on a single receptor molecule for ion-binding/recognition is vital for the new receptor design and needs to be well explored from experiment and theory. In this work, a new macrocyclic ion receptor (BEBUR) with three functional zones, including two ether holes and one biurea groups, is designed expecting to mutually enhance the ion-binding performance. The binding behaviors of BEBUR mainly for Cl- and Cs+ are deeply investigated by using density functional theoretical calculations. It is found that Cl-/Cs+ binding can be mutually enhanced and synergistically regulated via corresponding conformational changes of the receptor, well reflecting an electrical complementary matching and mutual reinforcement effect. Moreover, solvent effect calculations indicate that BEBUR may be an excellent candidate structure for Cl--binding with the enhancement of counter ion (Cs+) in water and toluene. In addition, visualization of intermolecular noncovalent interaction is used for analysis on the nature of the binding interactions between receptor and ions.

Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

Primary Arthrodesis with Retrograde Hindfoot Nail for Elderly Patients with Tibia Pilon Fractures and Psychiatric Illness.

BACKGROUND: Management of tibial pilon fracture in elderly patients with psychiatric illness remains challenging for orthopedic doctors because of patients' poor bone quality and inability for self-care. This study aimed to ascertain the viability and reliability of primary arthrodesis by using retrograde hindfoot nail for these difficult cases. METHODS: We retrospectively reviewed eight elderly consecutive patients (age older than 65 years) with tibial pilon fractures and psychiatric illness from January of 2012 to December of 2019 in our institute. Primary tibiotalocalcaneal arthrodesis with retrograde hindfoot nail was used as a definitive procedure. The bone union time, wound complication rate, ankle alignment, necessity for narcotic agents, and ambulation status were evaluated. RESULTS: The average length of follow-up was 22.25 months (range, 15-36 months). Additional bone grafting surgery was performed for one patient because of fusion-site nonunion 6 months postoperatively. Another patient required debridement and removal of posterior calcaneal screw because of implant prominence and local infection. Osseous union with angular deformity less than 10° was achieved in all patients finally. The average bone union time was 6.6 months (range, 4-12 months). In terms of walking ability, six patients were capable of outdoor ambulation (classes 2 and 3). Two patients required oral pain medication at the final visit. CONCLUSIONS: The current study involved only a small number of patients, and two of the eight cases encountered undesired complications (one local infection and one bone nonunion); however, we believe that our method may serve as a valuable alternative for the treatment of tibial pilon fractures in elderly patients with psychiatric illness, considering the specificity of this fragile population.

Gut microbiome signatures associated with type 2 diabetes in obesity in Mongolia.

Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the "Mongolian paradox." Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.

Microsurgical Management of Pineal Region Tumors.

BACKGROUND: Pineal tumors are rare, and the pineal region is a challenging surgical location for neurosurgeons. The present study aimed to investigate the effects of microsurgical management in patients with pineal region tumors and explore probable factors associated with preoperative hydrocephalus, postoperative hydrocephalus remission, and prolonged hospital length of stay (LoS). METHODS: A retrospective study of patients with pineal region tumors who underwent microsurgical management at the First Affiliated Hospital of Soochow University (Jiangsu, China) between 1 January 2010 and 31 October 2022 was conducted. RESULTS: Data from 36 patients were included in this study. The top 5 common symptoms included headache (58%), dizziness (44%), double vision (22%), vomiting (19%), and nausea (14%). Patients with a lower Karnofsky Performance Score (KPS), younger age, and larger maximum tumor diameters were more vulnerable to preoperative hydrocephalus. Preoperative hydrocephalus also led to a prolonged postoperative LoS (P = 0.021). Patients with a lower KPS score (P = 0.020) or larger maximum tumor diameters (P = 0.045) were more likely to achieve postoperative remission of hydrocephalus. Most postoperative complications led to increased hospital LoS. CONCLUSIONS: Microsurgical resection of pineal tumors yielded favorable long-term outcomes. Patients with a lower KPS score, younger age, and larger maximum tumor diameters were more vulnerable to preoperative hydrocephalus and prolonged LoS. Patients with a lower KPS score or larger tumor diameter were likely to achieve significant remission of hydrocephalus after tumor resection.

Exposure to ambient ozone and sperm quality among adult men in China.

BACKGROUND: Limited evidence exists regarding the association between ozone exposure and adverse sperm quality. We aimed to assess the association between ozone exposure and sperm quality, and identify susceptible exposure windows. METHODS: We recruited 32,541 men aged between 22 and 65 years old attending an infertility clinic in Wuhan, Hubei Province, China from 2014 to 2020. Ozone data were obtained from a satellite-based spatiotemporal model. Generalized linear models were used to estimate the association between ozone exposure and sperm quality parameters, including sperm concentration, sperm count, sperm total motility, and sperm progressive motility during the entire stage of sperm development (0-90 days before ejaculation) and three crucial stages (0-9 days, 10-14 days and 70-90 days before ejaculation). Stratified analyses were performed to evaluate whether associations varied by age, body mass index, and education levels. RESULTS: The final analysis included 27,854 adult men. A 10 µg/m3 increase in ozone concentrations during the entire stage of sperm development was associated with a -4.17 % (95 % CI: -4.78 %, -3.57 %) decrease in sperm concentration, -6.54 % (95 % CI: -8.03 %, -5.60 %) decrease in sperm count, -0.50 % (95 % CI: -0.66 %, -0.34 %) decrease in sperm total motility, and -0.07 % (95 % CI: -0.22 %, 0.09 %) decrease in sperm progressive motility. The associations were stronger during 70-90 days before ejaculation and among men with middle school and lower education for sperm concentration. CONCLUSIONS: Ozone exposure was associated with decreased sperm quality among Chinese adult men attending an infertility clinic. These results suggest that ozone may be a risk factor contributing to decreased sperm quality in Chinese men.

A wide-bandgap graphene-like structure C6BN with ultra-low dielectric constant.

This study introduces a new wide-bandgap graphene-like structure, denoted as C6BN, achieved by incorporating an eight-electron BN pair, substantially modifying its electronic properties. Utilizing extensive density functional calculations, we comprehensively analyzed the stability, electronic structure, mechanical properties, and optical-electrical characteristics of C6BN. Our investigations reveal the material's exceptional thermodynamic, mechanical, and dynamic stability. Notably, the calculated wide bandgap of 2.81 eV in C6BN, supported by analyses of energy levels, band structures, and density of states, positions it as a promising two-dimensional wide-bandgap semiconductor. Additionally, C6BN exhibits isotropic mechanical features, highlighting its inherent flexibility. Remarkably, our calculations indicate an ultra-low dielectric constant (k = 1.67) for C6BN, surpassing that of well-established third-generation semiconductors. Further exploration into the thermoelectric properties of C6BN demonstrates its promising performance, as evidenced by calculations of thermal conductivity (κ), power factor (P), and Seebeck coefficient (S). In summary, our findings underscore the significant potential of the proposed C6BN structure as a flexible two-dimensional material poised to drive future advancements in electronic and energy-related technologies.

Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Dorsal spanning plating for complex carpometacarpal fracture-dislocations: a retrospective case series.

We studied the outcome of dorsal spanning plate for complex carpometacarpal fracture-dislocation management as a feasible option in nine patients, even on delayed presentation with substantial metacarpal shortening. However, patients must be informed about the need for plate removal.

Realization of monolayer ZrTe5 topological insulators with wide band gaps.

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin-orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation.

BACKGROUND: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. CONCLUSIONS: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. BRIEF ACKNOWLEDGMENT: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002).

Dislodgment Effects of Different Cage Arrangements in Posterior Lumbar Interbody Fusion: A Finite Element Study.

The vertebral cage has been widely used in posterior lumbar interbody fusion. The risk of cage dislodgment is high for patients undergoing lumbar fusion surgery. Therefore, the main objective of this study was to use a lumbar fusion model to investigate the effects of cage dislodgment on different cage arrangements after PLIF. Finite element analysis was used to compare three PEEK cage placements, together with the fibula-type cage, with respect to the four kinds of lumbar movements. The results revealed that a horizontal cage arrangement could provide a better ability to resist cage dislodgment. Overall lumbar flexion movements were confirmed to produce a greater amount of cage slip than the other three lumbar movements. The lower part of the lumbar fusion segment could create a greater amount of cage dislodgment for all of the lumbar movements. Using an autograft with a fibula as a vertebral cage cannot effectively reduce cage dislodgment. Considering the maximum movement type in lumbar flexion, we suggest that a horizontal arrangement of the PEEK cage might be considered when a single PEEK cage is placed in the fusion segment, as doing so can effectively reduce the extent of cage dislodgment.

Assessment of Thermal Osteonecrosis during Bone Drilling Using a Three-Dimensional Finite Element Model.

Bone drilling is a common procedure used to create pilot holes for inserting screws to secure implants for fracture fixation. However, this process can increase bone temperature and the excessive heat can lead to cell death and thermal osteonecrosis, potentially causing early fixation failure or complications. We applied a three-dimensional dynamic elastoplastic finite element model to evaluate the propagation and distribution of heat during bone drilling and assess the thermally affected zone (TAZ) that may lead to thermal necrosis. This model investigates the parameters influencing bone temperature during bone drilling, including drill diameter, rotational speed, feed force, and predrilled hole. The results indicate that our FE model is sufficiently accurate in predicting the temperature rise effect during bone drilling. The maximum temperature decreases exponentially with radial distance. When the feed forces are 40 and 60 N, the maximum temperature does not exceed 45 °C. However, with feed forces of 10 and 20 N, both the maximum temperatures exceed 45 °C within a radial distance of 0.2 mm, indicating a high-risk zone for potential thermal osteonecrosis. With the two-stage drilling procedure, where a 2.5 mm pilot hole is predrilled, the maximum temperature can be reduced by 14 °C. This suggests that higher feed force and rotational speed and/or using a two-stage drilling process could mitigate bone temperature elevation and reduce the risk of thermal osteonecrosis during bone drilling.

Microecology of aerobic denitrification system construction driven by cyclic stress of sulfamethoxazole.

The construction of aerobic denitrification (AD) systems in an antibiotic-stressed environment is a serious challenge. This study investigated strategy of cyclic stress with concentration gradient (5-30 mg/L) of sulfamethoxazole (SMX) in a sequencing batch reactor (SBR), to achieve operation of AD. Total nitrogen removal efficiency of system increased from about 10 % to 95 %. Original response of abundant-rare genera to antibiotics was changed by SMX stress, particularly conditionally rare or abundant taxa (CRAT). AD process depends on synergistic effect of heterotrophic nitrifying aerobic denitrification bacteria (Paracoccus, Thauera, Hypomicrobium, etc). AmoABC, napA, and nirK were functionally co-expressed with multiple antibiotic resistance genes (ARGs) (acrR, ereAB, and mdtO), facilitating AD process. ARGs and TCA cycling synergistically enhance the antioxidant and electron transport capacities of AD process. Antibiotic efflux pump mechanism played an important role in operation of AD. The study provides strong support for regulating activated sludge to achieve in situ AD function.

Direct Photocatalytic Methane Oxidation to Formaldehyde by N Doping Co-Decorated Mixed Crystal TiO2.

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

Changes of peripheral blood α-L-fucosidase activity in patients with rheumatoid arthritis: a cross-sectional study.

Background: Rheumatoid arthritis (RA), a systemic autoimmune disease with approximately 1% prevalent population worldwide, which the etiology is still unclear. RA cannot be completely cured at present, which seriously affects the quality of life of patients. This study is to compare the peripheral blood α-L-fucosidase (AFU) between RA and healthy persons. Methods: A cross-sectional study was performed using total of 96 patients with RA served as case group and another 94 age-matched healthy volunteers served as a control group. AFU assay is detected by continuous monitoring method using Toshiba TBA-120FR (Tokyo, Japan) fully automatic biochemical analyzer in Japan, and the reagent is purchased from Zhejiang Quark Biological Company (Zhejiang, China). Statistical analysis was performed using SPSS 24.0 (SPSS, Inc., Chicago, IL, USA). Results: AFU activity in peripheral blood of RA patients were lower than healthy controls. The higher AFU activity, the shorter the course of disease (r=-0.2790, P=0.0065). The activity of lactate dehydrogenase in patients with RA is higher than that of healthy control, but the activity of acetylcholinesterase is lower than that of normal people. Finally, AFU activity was negatively correlated with the activity of lactate dehydrogenase (r=-0.2381, P=0.0208) and positively correlated with the activity of acetylcholinesterase (r=0.2985, P=0.0035). Conclusions: Changes of peripheral blood AFU activity might be associated with progression of disease in RA patients. The changes of AFU activity may lead to disturbances in glucose and lipid metabolism.

Nerve Bypass Surgery for Spinal Cord Reconstruction.

OBJECTIVE: Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves into the spinal cord. METHODS: Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of 2 pairs of intercostal nerves from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. RESULTS: Six of the 8 (75%) patients demonstrated motor and sensory improvements, based on the American SCI Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid leakage after surgery; however, only 1 patient complained of a headache. CONCLUSIONS: Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation.

Imidazoles are Tunable Nucleofuges for Developing Tyrosine-Reactive Electrophiles.

Imidazole-1-sulfonyl and -sulfonate (imidazylate) are widely used in synthetic chemistry as nucleofuges for diazotransfer, nucleophilic substitution, and cross-coupling reactions. The utility of these reagents for protein bioconjugation, in contrast, have not been comprehensively explored and important considering the prevalence of imidazoles in biomolecules and drugs. Here, we synthesized a series of alkyne-modified sulfonyl- and sulfonate-imidazole probes to investigate the utility of this electrophile for protein binding. Alkylation of the distal nitrogen activated the nucleofuge capability of the imidazole to produce sulfonyl-imidazolium electrophiles that were highly reactive but unstable for biological applications. In contrast, arylsulfonyl imidazoles functioned as a tempered electrophile for assessing ligandability of select tyrosine and lysine sites in cell proteomes and when mated to a recognition element could produce targeted covalent inhibitors with reduced off-target activity. In summary, imidazole nucleofuges show balanced stability and tunability to produce sulfone-based electrophiles that bind functional tyrosine and lysine sites in the proteome.