Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the ...paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury.
We randomly assigned 36 patients who had had unilateral arm paralysis for more than 5 years to undergo C7 nerve transfer plus rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl-Meyer upper-extremity scale (scores range from 0 to 66, with higher scores indicating better function). Results The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft.
The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft.
In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, 13004466 .).
In order to study the flow behaviors of an Al-Zn-Mg-Cu alloy at elevated temperatures, uniaxial tensile tests were carried out in wide deformation temperature and strain rate ranges. The flow stress ...rapidly increases to a peak value and then slightly decreases with the increased strain, and the dynamic recovery (DRV) is the primary softening mechanism. A unified constitutive model based on dislocation density was developed. An iterative procedure was implemented into the developed model to describe the flow behaviors at time-variant deformation conditions (e.g. the strain rate is changed during hot deformation). The predicted flow stresses were in accord with the experimental results, suggesting that the flow behaviors of the studied Al alloy at elevated temperatures can be well reproduced by the developed model. Meanwhile, the variations of the product of the instantaneous work hardening (WH) rate and stress caused by dislocation evolution, the dislocation density changing rate, as well as the dislocation mean free path, were given to analyze the WH and DRV mechanisms of Al-Zn-Mg-Cu alloy.
Exploring novel multifunctional rare earth materials is very important because these materials have fundamental interests, such as new structural facts and connecting modes, as well as potential ...technological applications, including optics, magnetic properties, sorption, and catalytic behaviors. Especially, employing these nanomaterials for sensing or catalytic reactions is still very challenging. Herein, a new superstable, anionic terbium‐metal–organic‐framework, H2N(CH3)2Tb(cppa)2(H2O)2, (China Three Gorges University (CTGU‐1), H2cppa = 5‐(4‐carboxyphenyl)picolinic acid), is successfully prepared, which can be used as a turn‐on, highly‐sensitive fluorescent sensor to detect Eu3+ and Dy3+, with a detection limitation of 5 × 10−8 and 1 × 10−4m in dimethylformamide, respectively. This result represents the first example of lanthanide‐metal–organic‐frameworks (Ln‐MOF) that can be employed as a discriminative fluorescent probe to recognize Eu3+ and Dy3+. In addition, through ion exchanging at room temperature, Ag(I) can be readily reduced in situ and embedded in the anionic framework, which leads to the formation of nanometal‐particle@Ln‐MOF composite with uniform size and distribution. The as‐prepared Ag@CTGU‐1 shows remarkable catalytic performance to reduce 4‐nitrophenol, with a reduction rate constant κ as large as 2.57 × 10−2 s−1; almost the highest value among all reported noble‐metal‐nanoparticle@MOF composites.
A new porous, anionic Tb‐metal–organic‐framework, China Three Gorges University (CTGU‐1), can serve as a turn‐on sensor for detection of Eu3+ and Dy3+, with different detection limits. Additionally, spontaneous in situ reduction and immobilization of ion‐exchanged Ag(I) to Ag nanoparticles in the anionic framework result in an Ag@CTGU‐1 composite, which can remarkably catalyze the reduction of 4‐nitrophenol.
New porous anionic Ln-MOFs, namely, Me 2 NH 2 Ln(CPA) 2 (H 2 O) 2 (Ln = Eu, Gd), have been prepared through the self-assembly of 5-(4-carboxy phenyl)picolinic acid (H2CPA) and lanthanide ions. ...They feature open anionic frameworks with 1-D hydrophilic channels and exchangeable dimethylamine ions. The Eu phase could detect Fe3+ ions with high selectivity and sensitivity in either aqueous solution or biological condition. The ratios of lanthanide ions on this structure platform could be rationally tuned to not only achieve dichromatic emission colors with linear correlation but also attain three primary colors (RGB) and even white light with favorable correlated color temperature. Furthermore, the Ag(I)-exchanged phases can be readily reduced to afford Ag nanoparticles. The as-prepared Ag@Ln-MOFs composite shows highly efficient catalytic performance for the reduction of 4-nitrophenol.
Abstract
Enhancing the intrinsic activity and space time yield of Cu based heterogeneous methanol synthesis catalysts through CO
2
hydrogenation is one of the major topics in CO
2
conversion into ...value-added liquid fuels and chemicals. Here we report inverse ZrO
2
/Cu catalysts with a tunable Zr/Cu ratio have been prepared via an oxalate co-precipitation method, showing excellent performance for CO
2
hydrogenation to methanol. Under optimal condition, the catalyst composed by 10% of ZrO
2
supported over 90% of Cu exhibits the highest mass-specific methanol formation rate of 524 g
MeOH
kg
cat
−1
h
−1
at 220 °C, 3.3 times higher than the activity of traditional Cu/ZrO
2
catalysts (159 g
MeOH
kg
cat
−1
h
−1
). In situ XRD-PDF, XAFS and AP-XPS structural studies reveal that the inverse ZrO
2
/Cu catalysts are composed of islands of partially reduced 1–2 nm amorphous ZrO
2
supported over metallic Cu particles. The ZrO
2
islands are highly active for the CO
2
activation. Meanwhile, an intermediate of formate adsorbed on the Cu at 1350 cm
−1
is discovered by the in situ DRIFTS. This formate intermediate exhibits fast hydrogenation conversion to methoxy. The activation of CO
2
and hydrogenation of all the surface oxygenate intermediates are significantly accelerated over the inverse ZrO
2
/Cu configuration, accounting for the excellent methanol formation activity observed.
•The dynamic recrystallization behavior of a typical nickel-based superalloy is investigated.•The segmented models are proposed to describe the kinetics of DRX for the studied superalloy.•The ...dynamically recrystallized grain size can be well characterized by a function of Z parameter.
The dynamic recrystallization (DRX) behavior of a typical nickel-based superalloy is investigated by the hot compression tests. Based on the conventional DRX kinetics model, the volume fractions of DRX are firstly estimated. Results show that there is an obvious deviation between the experimental and predicted volume fractions of DRX when the forming temperature is below 980°C, which is induced by the slow dynamic recrystallization rate under low forming temperatures. Therefore, the segmented models are proposed to describe the kinetics of DRX for the studied superalloy. Comparisons between the experimental and predicted results indicate that the proposed segmented models can give an accurate and precise estimation of the volume fractions of DRX for the studied superalloy. In addition, the optical observation of the deformed microstructure confirms that the dynamically recrystallized grain size can be well characterized by a power function of Zener–Hollumon parameter.
The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory ...pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia‐telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1‐Bcl‐2 autophagy‐regulatory complex formation in a ROS‐dependent fashion. We further demonstrate that CHK2‐mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2−/− mice display aggravated infarct phenotypes and reduced Beclin 1 p‐Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2‐induced autophagy in cell survival. Taken together, these results indicate that the ROS‐ATM‐CHK2‐Beclin 1‐autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress‐induced tissue damage.
Synopsis
Whether hypoxia and nutrient starvation are coupled to cellular autophagy remains unclear. Here, DNA damage response kinases ATM and CHK2 are shown to trigger autophagy in response to reactive oxygen species (ROS) accumulation, suggesting a novel physiological adaptation pathway toward metabolic stress.
Depletion of CHK2 or ATM impairs oxidative stress‐induced autophagy in MEFs.
CHK2 binds and phosphorylates Beclin1 at Ser90/Ser93, suppressing Beclin1‐Bcl‐2 autophagy regulatory complex formation.
CHK2‐induced autophagy limits intracellular ROS levels by clearing damaged mitochondria.
CHK2‐induced autophagy protects against cell death and tissue damage following cerebral ischemia.
ROS accumulation activates protective autophagy to prevent stress‐induced tissue damage.
Three new multi-nuclear Cu(II) complexes have been successfully synthesized by the one-pot reaction of a bis(salamo)-based ligand H3L and different copper(II) salts and characterized structurally.
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•Three new multi-nuclear Cu(II) complexes have been successfully synthesized and characterized structurally.•Complex 3 is a novel penta-nuclear structure derived of the ligand (HL)2- units.•Effects of counteranions and fluorescence properties were also investigated.
Three new multi-nuclear Cu(II) complexes, Cu4(L)2(CH3OH)2(NO3)2·2CH3OH (1), Cu4(L)2(CH3OH)(CH3CN)(ClO4)2·2CH3OH (2) and Cu4(HL)2(μ2-Cl)2Cl2(CH3CH2OH)2CuCl2·CHCl3 (3) have been successfully synthesized by the one-pot reaction of a bis(salamo)-based ligand H3L with Cu(NO3)2·3H2O, Cu(ClO4)2·6H2O and CuCl2·2H2O, respectively. Complexes 1 and 2 are monoclinic systems including four Cu(II) atoms with two completely deprotonated ligand (L)3- units, which form centrosymmetric helical molecules. Complex 3 is triclinic system including five Cu(II) atoms with two incompletely deprotonated ligand (HL)2- units, which forms an expanded structural molecule. Complexes 1–3 have been characterized by elemental analyses, IR, UV–Vis spectroscopy and single crystal X-ray crystallography. In addition, supramolecular interactions, Hirshfeld surfaces analyses, effects of counteranions and fluorescence properties were also investigated.
Background and Purpose
Patients suffering from trigeminal neuralgia are often accompanied by anxiety and depression. Microglia‐mediated neuroinflammation is involved in the development of neuropathic ...pain and anxiodepression pathogenesis. Whether and how microglia are involved in trigeminal neuralgia‐induced anxiodepression remains unclear.
Experimental Approach
Unilateral constriction of the infraorbital nerve (CION) was performed to establish trigeminal neuralgia in rat and mouse models. Mechanical allodynia and anxiodepressive‐like behaviours were measured. Optogenetic and pharmacological manipulations were employed to investigate the role of hippocampal microglia in anxiety and depression caused by trigeminal neuralgia.
Key Results
Trigeminal neuralgia activated ipsilateral but not contralateral hippocampal microglia, up‐regulated ipsilateral hippocampal ATP and interleukin‐1β (IL‐1β) levels, impaired ipsilateral hippocampal long‐term potentiation (LTP) and induced anxiodepressive‐like behaviours in a time‐dependent manner in rodents. Pharmacological or optogenetic inhibition of ipsilateral hippocampal microglia completely blocked trigeminal neuralgia‐induced anxiodepressive‐like behaviours. Activation of unilateral hippocampal microglia directly elicited an anxiodepressive state and impaired hippocampal LTP. Knockdown of ipsilateral hippocampal P2X7 receptors prevented trigeminal neuralgia‐induced microglial activation and anxiodepressive‐like behaviours. Furthermore, we demonstrated that microglia‐derived IL‐1β mediated microglial activation‐induced anxiodepressive‐like behaviours and LTP impairment.
Conclusion and Implications
These findings suggest that priming of microglia with ATP/P2X7 receptors in the ipsilateral hippocampus drives pain‐related anxiodepressive‐like behaviours via IL‐1β. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia‐induced anxiety and depression was uncovered. The approaches targeting microglia and P2X7 signalling might offer novel therapies for trigeminal neuralgia‐related anxiety and depressive disorder.
Trigeminal neuralgia activates ipsilateral hippocampal microglia by ATP/P2X7 receptor interaction which impairs ipsilateral hippocampal long‐term potentiation (LTP) via interleukin‐1β (IL‐1β). Microglial purinergic inflammatory responses and the neuronal plasticity changes in the ipsilateral hippocampal CA1 area may be a key pathogenesis of anxiodepression caused by trigeminal neuralgia. The approaches targeting microglia and P2X7 receptor signalling might offer novel therapies for trigeminal neuralgia‐related anxiety and depressive disorder.
Previous studies suggest that poor sleep quality or abnormal sleep duration may be associated with frailty. Here we test the associations of sleep disturbances with both frailty and pre-frailty in an ...elderly population.
Participants included 1726 community-dwelling elders aged 70-87 years. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep disturbances. Frailty was defined using phenotype criteria. Logistic regression models were used to estimate odds ratio of the associations.
The average PSQI score was 5.4 (SD, 3.1). Overall 43.6% of the participants had poor sleep quality (PSQI> 5), 8.2% had night sleep time ≤ 5 h, and 27.8% had night sleep time ≥ 9 h. The prevalence of frailty and pre-frailty was 9.2 and 52.8%, respectively. The proportions of PSQI> 5 increased with the severity of frailty status (robust: pre-frail: frail, 34.5%: 48%: 56.1%, P < 0.001). After adjustment for multiple potential confounders, poor sleep quality (PSQI> 5) was associated with higher odds of frailty (OR = 1.78, 95% CI 1.19-2.66) and pre-frailty (OR = 1.51, 95% CI 1.20-1.90). Sleep latency, sleep disturbance, and daytime dysfunction components of PSQI measurements were also associated with frailty and pre-frailty. In addition, sleep time 9 h/night was associated with higher odds of frailty and pre-frailty.
We provided preliminary evidences that poor sleep quality and prolonged sleep duration were associated with being frailty and pre-frailty in an elderly population aged 70-87 years. The associations need to be validated in other elderly populations.
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