Electron transport through two interacting channels in Azurin-based solid-state junctions.

The fundamental question of "what is the transport path of electrons through proteins?" initially introduced while studying long-range electron transfer between localized redox centers in proteins in vivo is also highly relevant to the transport properties of solid-state, dry metal-protein-metal junctions. Here, we report conductance measurements of such junctions, Au-(Azurin monolayer ensemble)-Bismuth (Bi) ones, with well-defined nanopore geometry and ~103 proteins/pore. Our results can be understood as follows. (1) Transport is via two interacting conducting channels, characterized by different spatial and time scales. The slow and spatially localized channel is associated with the Cu center of Azurin and the fast delocalized one with the protein's polypeptide matrix. Transport via the slow channel is by a sequential (noncoherent) process and in the second one by direct, off-resonant tunneling. (2) The two channels are capacitively coupled. Thus, with a change in charge occupation of the weakly coupled (metal center) channel, the broad energy level manifold, responsible for off-resonance tunneling, shifts, relative to the electrodes' Fermi levels. In this process, the off-resonance (fast) channel dominates transport, and the slow (redox) channel, while contributing only negligibly directly, significantly affects transport by intramolecular gating.

Disordered Ballistic Bismuth Nano-waveguides for Highly Efficient Thermoelectric Energy Conversion.

Junctions based on electronic ballistic waveguides, such as semiconductor nanowires or nanoribbons with transverse structural variations in the order of a large fraction of their Fermi wavelength, are suggested as highly efficient thermoelectric (TE) devices. Full harnessing of their potential requires a capability to either deterministically induce structural variations that tailor their transmission properties at the Fermi level or alternatively to form waveguides that are disordered (chaotic) but can be structurally modified continuously until favorable TE properties are achieved. Well-established methods to realize either of these routes do not exist. Here, disordered bismuth (Bi) waveguides are reported, which are both formed and structurally tuned by electromigration until their efficiency as TE devices is maximized. In accordance with theory, the conductance of the most efficient TE waveguides is in the sub quantum of conductance regime. The stability of these structures is found to be substantially higher than other actively studied devices such as single molecule junctions.

Water-soluble coenzyme q10 inhibits nuclear translocation of apoptosis inducing factor and cell death caused by mitochondrial complex I inhibition.

The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10) on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS) production by dihydroethidine (DHE) and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF) were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

Insight into Oxygen Transport in Proton Exchange Membrane Water Electrolyzers by In Situ X-Ray Characterization.

The proton exchange membrane water electrolyzer (PEMWE) is one of the most promising electrochemical energy conversion devices for hydrogen production, while still limited by performance bottlenecks at high current densities, due to the lack of mass transfer insights. To investigate the mechanisms of oxygen transport inside the PEMWE at high current density and its relation to electrolytic performance. Operational in situ x-ray imaging is utilized to simultaneously characterize the bubble behavior and voltage response in a novel designed visual mini-cell, and it is identified that oxygen evolution and transport in the PEMWE follow the process of bubble nucleation, growth, and detachment. Based on the results of mini-cells with three porous transport layers (PTLs) up to 9 A cm-2 operation, it revealed that critical current densities exist for both carbon-based and titanium-based PTLs. Once exceeding the critical current density, the cell voltage can no longer be stabilized and the cell exhibits a significant oxygen overpotential. To illustrate this, the concept of interfacial separation zone (ISZ) is first proposed, which is an effective pathway for bubble growth and separation and the pattern of the ISZ exhibits specific regimes with the critical current density. Ultimately, a new approach for better understanding the mechanisms of oxygen transport is revealed.

Molecular ensemble junctions with inter-molecular quantum interference.

We report of a high yield method to form nanopore molecular ensembles junctions containing ~40,000 molecules, in which the semimetal bismuth (Bi) is a top contact. Conductance histograms of these junctions are double-peaked (bi-modal), a behavior that is typical for single molecule junctions but not expected for junctions with thousands of molecules. This unique observation is shown to result from a new form of quantum interference that is inter-molecular in nature, which occurs in these junctions since the very long coherence length of the electrons in Bi enables them to probe large ensembles of molecules while tunneling through the junctions. Under such conditions, each molecule within the ensembles becomes an interference path that modifies via its tunneling phase the electronic structure of the entire junction. This new form of quantum interference holds a great promise for robust novel conductance effects in practical molecular junctions.

Damage to the blood­brain barrier and activation of neuroinflammation by focal cerebral ischemia under hyperglycemic condition.

Hyperglycemia aggravates brain damage caused by cerebral ischemia/reperfusion (I/R) and increases the permeability of the blood­brain barrier (BBB). However, there are relatively few studies on morphological changes of the BBB. The present study aimed to investigate the effect of hyperglycemia on BBB morphological changes following cerebral I/R injury. Streptozotocin­induced hyperglycemic and citrate­buffered saline­injected normoglycemic rats were subjected to 30 min middle cerebral artery occlusion. Neurological deficits were evaluated. Brain infarct volume was assessed by 2,3,5­triphenyltetrazolium chloride staining and BBB integrity was evaluated by Evans blue and IgG extravasation following 24 h reperfusion. Changes in tight junctions (TJ) and basement membrane (BM) proteins (claudin, occludin and zonula occludens­1) were examined using immunohistochemistry and western blotting. Astrocytes, microglial cells and neutrophils were labeled with specific antibodies for immunohistochemistry after 1, 3 and 7 days of reperfusion. Hyperglycemia increased extravasations of Evan's blue and IgG and aggravated damage to TJ and BM proteins following I/R injury. Furthermore, hyperglycemia suppressed astrocyte activation and damaged astrocytic endfeet surrounding cerebral blood vessels following I/R. Hyperglycemia inhibited microglia activation and proliferation and increased neutrophil infiltration in the brain. It was concluded that hyperglycemia­induced BBB leakage following I/R might be caused by damage to TJ and BM proteins and astrocytic endfeet. Furthermore, suppression of microglial cells and increased neutrophil infiltration to the brain may contribute to the detrimental effects of pre­ischemic hyperglycemia on the outcome of cerebral ischemic stroke.

The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply.

Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key role in selenium (Se) transport throughout the body. Development of a Sel P knockout mouse model has supported this notion and initial studies have indicated that selenium supply to various tissues is differentially affected by genetic deletion of Sel P. Se in the form of the amino acid, selenocysteine, is incorporated into selenoproteins at UGA codons. Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in mice affected levels of the mRNAs encoding all known members of the murine selenoprotein family, as well as three non-selenoprotein factors involved in their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2 (SBP2) and SECp43. Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes. We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

Streptozotocin-induced diabetes causes astrocyte death after ischemia and reperfusion injury.

Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One contributing factor is enhanced acidosis during ischemia. Astrocytes are vulnerable to hypoxia under acidic conditions in vitro and may be targets of ischemia under diabetic conditions. The objective of this study was to determine whether diabetes would cause damage to astrocytes after an ischemic brain injury in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results showed that ischemia caused activation of astrocytes in nondiabetic rats. In contrast, diabetes caused astrocyte activation in early stage of reperfusion and astrocyte death in late stage of reperfusion. Remarkable astrocyte death was preceded by increased DNA oxidation. Further studies revealed that increased astrocyte damage coincided with enhanced production of free radicals. These data suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in neurons.

Risk factors analysis of mirror aneurysms: A multi-center retrospective study based on clinical and demographic profile of patients.

As a special subgroup of multiple intracranial aneurysms, mirror aneurysms are located bilaterally on the corresponding intracranial arteries. The current study sought to compare the clinical and demographic features of patients harboring mirror aneurysm, and to elucidate the corresponding risk factors. We performed a retrospective cohort study of 2641 intracranial aneurysms patients, who were admitted to our hospitals between January 2005 and June 2014. Patients were subdivided into three groups based on the inclusion criteria: (i) single (n=2250); (ii) non-mirror multiple (n=285); and (iii) mirror aneurysms (n=106). Clinical and demographic files of the three groups were collected and compared, and medical histories including stroke, hyperlipemia, hypertension, hyperglycemia, valvular heart disease were considered as potential risk factors. Potential morphological reasons for mirror cerebral aneurysms rupture, including aneurysms size, irregular walls and cerebral hemispheric dominance, were also compared. Our data showed that the male to female ratio of mirror aneurysms patients was 1:3.61, which was significantly different from that of single aneurysm (1:1.27) and multiple aneurysms (1:2.00). The prevalence of mirror aneurysms in women is higher than that in men (P<0.001). Older patients (especially 60-69 years old) also appear to be more vulnerable to mirror aneurysm than single aneurysm (P<0.001). In 84 mirror aneurysm patients the aneurysms were located on the internal carotid arteries (79.2%), most typically at the PComA or in the Cavernous ICA. Patients with medical history of hyperlipemia appear to have an increased risk of harboring mirror aneurysms. Larger aneurysm size and presence of an irregular aneurysm wall appear to be the morphological factors that predispose for mirror aneurysms rupture.

Early efficacy analysis on arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation / 中国骨伤

OBJECTIVE@#To investigate the early efficacy of arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation.@*METHODS@#From January 2019 to January 2021, 17 patients with recurrent anterior dislocation of shoulder who underwent arthroscopic autologous osteochondral grafting were selected, including 12 males and 5 females, ranging in age from 17 to 55 years old, with a mean of (32.88±12.33) years old. Rowes rating system for Bankart repair(Rowe), Oxford Shoulder Instability Score (OSIS) and Simple Shoulder Test (SST) were compared before operation, 6 months after operation and at the latest follow-up. OSIS and SST used to evaluate shoulder function were recorded before surgery and at the latest follow-up. The shoulder mobility and intraoperative and postoperative complications were also recorded.@*RESULTS@#All 17 patients were followed up, and the duration ranged from 7 to 25 months, with a mean of (18.4±5.4) months. During the follow-up period, there was no re-dislocation, no vascular or nerve injury. Rowe score increased from 26.2±6.0 before operation to 74.4±4.0 and 82.4±3.1 after 6 months and the latest follow-up. There was significant difference in Rowe score between different time points after operation and before operation (P<0.05). The OSIS increased from 37.0±3.6 before operation to 47.4±2.6 and 52.7±2.6 after 6 months and the latest follow-up. There was significant difference in OSIS between different time points after operation and before operation (P<0.05). The SST score increased from 6.8±0.7 before operation to 9.8±0.8, 11.6±2.6 after 6 months and the latest follow-up. There was significant difference in SST score between different time points after operation and before operation (P<0.05). At the latest follow-up, the lateral external rotation and abduction external rotation activities of the patient were significantly improved compared with those before operation.@*CONCLUSION@#This study provides preliminary evidence that arthroscopic autologous osteochondral grafting can achieve satisfactory early clinical outcomes and stability in patients with recurrent anterior shoulder dislocation with glenoid fracture and defect less than <20%, which is a reliable and effective procedure.

Hyperglycemia increases superoxide production in the CA1 pyramidal neurons after global cerebral ischemia.

Transient global cerebral ischemia results in selective neuronal death in the vulnerable hippocampal CA1 pyramidal neurons in a delayed manner. Hyperglycemia accelerates and exacerbates neuronal damage in this region. The object of this study was to determine whether hyperglycemia-enhanced damage is associated with increased production of superoxide anion after ischemia. The results showed that hyperglycemic ischemia caused a significant increase of superoxide production in the hippocampal CA1 neurons compared to normoglycemic animals after 18 h of recirculation, suggesting that enhanced superoxide anion production may mediate the hyperglycemia-accelerated and -enhanced neuronal death in the hippocampal CA1 area after ischemia and reperfusion.

Progress on the treatment of recurrent anterior dislocation of shoulder with bone defect / 中国骨伤

Recurrent anterior dislocation of shoulder with bone defect is one of the common diseases of shoulder joint. How to effectively repair glenoid bone defect and reduce recurrence rate of shoulder dislocation is a problem that clinicians focus on. Bone grafting could stimulate bone, promote bone regeneration and bone remodeling, and restore the normal anatomical structure of glenoid. Among them, Bristow-Latarjet procedure is a classic operation for recurrent shoulder dislocation. Latarjet procedure could repair larger glenoid bone defects, but with higher surgical skills for surgeons;autogenous iliac grafting is the first choice for revision once Latarjet procedure failed;osteochondral grafting (autogenous and allogenous) has certain advantages in reconstructing original articular surface and preventing joint degeneration, but autologous osteochondral grafting may cause secondary injury, while immune rejection is difficult to avoid for allogenous osteochondral grafting. With the improvement of composite materials, and the mechanism of bone regeneration and remodeling, as well as the advantages and disadvantages of bone grafting, tissue engineering technology may become an effective method for the treatment of glenoid bone defect in the future.

Suture technique for rotator cuff tears' repair under arthroscopic / 中国骨伤

Shoulder arthroscopic as a conventional method usually is applied to repair rotator cuff tears. In clinical, plenty single-row, double-row and transosseous tunnels suture technique are performed, but the ideal suture technique for rotator cuff repair is not found. Compared with single-row, double-row has better strength in biomechanics property. As the two best suture technique among the single-row, massive cuff stitch and modified Mason-Allen suture have the strongest biomechanics property. Clinical trials indicate that double-row could improve healing rates, but there are no significant difference in clinical outcome functional scores. Transosseous tunnel techniques possess a better bio-mechanic property, which could improve regional micro-environment and induce tendon-bone healing. Transosseous tunnel techniques are better for small to media size rotator cuff tears and osteoporosis patient. The author suggest that optimal rotator cuff repair technique should performed according to skill of performer and individual of patient by analysing bio-mechanic properties, clinical outcome, operative complexity and patient situation. The technique should follow simple opertaion, rapid, less trauma, stable fixation and utility to perform.

Diabetes activates cell death pathway after transient focal cerebral ischemia.

It is well known that diabetes aggravates brain damage in experimental and clinical stroke subjects. Diabetes accelerates maturation of neuronal damage, increases infarct volume, and induces postischemic seizures. The mechanism by which diabetes increases ischemic brain damage is still elusive. Our previous experiments indicate that mitochondria dysfunction may play a role in neuronal death. The objective of this study is to determine whether streptozotocin-induced diabetes activates cell death pathway after a brief period of focal cerebral ischemia. Both diabetic and nondiabetic rats were subjected to 30 min of transient middle cerebral artery occlusion, followed by 0, 0.5, 3, and 6 h of reperfusion. We first determined the pathological outcomes after 7 days of recovery by histopathology, and then detected key components of programmed cell death pathway using immunocytochemistry coupled with confocal laser-scanning microscopy and Western blot analysis. The results show that the cytosolic cytochrome c increased mildly after reperfusion in nondiabetic samples. This increase was markedly enhanced in diabetic rats in both ischemic focus and penumbra. Subsequently, caspase-3 was activated and poly-ADP ribose polymerase (PARP) was cleaved. Our results suggest that activation of apoptotic cell death pathway may play a pivotal role in exaggerating brain damage in diabetic subjects.

Diabetes increases expression of ICAM after a brief period of cerebral ischemia.

The objective of present study was to determine whether leukocyte-endothelial cell adhesive molecule, intercellular cell adhesion molecule-1 (ICAM-1) was increased after ischemia in diabetic rats. The immunohistochemistry of ICAM showed that numbers of ICAM-1 positively stained microvessels in the cortex were markedly increased at 3 days of reperfusion in diabetic, but not in non-diabetic rats. These were further confirmed by Western analysis. Western analyses also showed that interlukin-1beta (IL-1beta), but not TNF-alpha, was increased at 3 days of the reperfusion in diabetic rats. The results suggest that inflammatory responses may mediate diabetic hyperglycemia-aggravated brain damage induced by ischemia and reperfusion.

Induction of heat shock proteins by hyperglycemic cerebral ischemia.

Hyperglycemia worsens the neuronal death induced by cerebral ischemia. A previous study demonstrated that diabetic hyperglycemia suppressed the expression of heat shock protein 70 (HSP70) in the liver. The objective of this study is to determine whether hyperglycemia exacerbates ischemic brain damage by suppressing the expression of heat shock proteins (HSPs) in the brain. Both normoglycemic and hyperglycemic rats were subjected to a transient global cerebral ischemia of 15 min and followed by 0.5, 1 and 3 h of reperfusion. The expression of stress-related genes and levels of HSP proteins were determined by DNA microarray, immunocytochemistry and Western blot analyses. The results showed that hyperglycemic ischemia upregulated the expressions of hsp70, hsp90A, hsp90B, heat shock cognate 71 kD protein (hsc70) and mthsp70. Protein levels of HSP70 and HSP60 were enhanced by hyperglycemia compared with normoglycemia. The results suggested that hyperglycemia-exacerbated ischemic brain damage is not mediated by the suppression of the HSPs. The increased levels of HSPs and mthsp70 suggest that the cell and the mitochondrion had strong stress responses to hyperglycemic ischemia.

Bongkrekic acid ameliorates ischemic neuronal death in the cortex by preventing cytochrome c release and inhibiting astrocyte activation.

Mitochondrial release of cytochrome c (cyt-c) plays a critical role in initiating cell death after cerebral ischemia. The objective of this study was to determine whether bongkrekic acid (BKA) ameliorates ischemic neuronal damage by inhibiting the release of cyt-c. These results showed that a 10min period of global ischemia caused neuronal death, increased the release of cyt-c and activated astrocytes in the cortex and CA1. BKA treatment reduced ischemic-induced neuronal death, prevented cyt-c release and inhibited astrocyte activation in the cortex, but not in the CA1. These results suggest that the neuroprotective effect of BKA is associated with its ability to prevent cyt-c release and to inhibit astrocyte activation.

LOXL null mice demonstrate selective dentate structural changes but maintain dentate granule cell and CA1 pyramidal cell potentiation in the hippocampus.

Lysyl oxidase-like protein (LOXL), part of the lysyl oxidase copper-dependent amine oxidase family, is expressed in the extracellular matrix and in the nucleus. It likely plays a role in cross-linking collagen and elastin, possibly modulating cellular functions. Immunohistochemical studies show the presence of LOXL in the pyramidal cell layer of the hippocampus; and in this study, we report that cells in the granule cell layer have significantly smaller somas in LOXL -/- compared to LOXL +/+ mice. In addition we tested the hypothesis that these structural alterations in the dentate granule layer were associated with synaptic efficacy and thus muted long-term potentiation in mice lacking the protein. Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice. Potentiation in the CA1 cell layer of 10 LOXL -/- and 8 LOXL +/+ mice was 191.0+/-9.3% and 181.6+/-9.1%, respectively (mean+/-S.E.M.). Dentate potentiation was 120.8+/-7.0% and 121.0+/-3.4% in 11 LOXL -/- and 11 LOXL +/+ mice, respectively. No phenotypic difference in potentiation of population spike amplitude (or in EPSP slope) in either layer was observed. Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP.

Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice / 中国实验方剂学杂志

Objective:To study the effect of Schisandrae Chinensis Fructus lignans (SCL) on learning and memory ability of D-galactose（D-gal）-induced aging model mice. Method:ICR mice were randomly divided into 4 groups: normal group (distilled water, subcutaneous injection with normal saline), model group (distilled water, subcutaneous injection with 200 mg·kg-1D-gal), piracetam group (oral administration with 200 mg·kg-1 piracetam, subcutaneous injection with 200 mg·kg-1D-gal), low-dose SCL group (oral administration with 50 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1 D-gal), medium-dose SCL group (oral administration with 100 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1D-gal), high-dose SCL group (oral administration with 200 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1 D-gal). The drugs were administered continuously for 10 weeks. Dark test and Morris water maze test were performed to observe the effect of SCL on the learning and memory ability of D-gal-induced aging mice. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in mouse brain tissue were detected by chemical colorimetry. The expressions of peroxiredoxin-6（Prdx6） and glutathione peroxidase 1（GSH-Px1） mRNA in mouse brain tissue were detected by polymerase chain reaction (PCR). The expressions of Prdx6 and GSH-Px1 protein in mouse tissues were detected by Western blot. Result:In behavioral experiments, compared with normal group, the number of dark avoidance errors in model group significantly increased (P<0.05), the latency was significantly reduced (P<0.01), and the number of mouse passes and the target quadrant residence time were significantly reduced (P<0.01), which can be used as an indicator of successful modeling. Compared with the model group, the number of errors in the piracetam group, and medium and high-dose SCL groups was significantly reduced (P<0.05，P<0.01), and the latency was significantly prolonged (P<0.05，P<0.01). At the same time, the number of water maze passes and the target quadrant retention time in the high-dose SCL group increased significantly (P<0.01). The results of biochemical indicators showed that compared with normal group, the SOD activity in brain tissue of model group mice was significantly reduced (P<0.01), while the MDA content was increased (P<0.05). Compared with the model group, SOD activity in the brain tissues of piracetam group, and low, medium and high-dose piracetam groups was significantly increased (P<0.05), whereas the level of MDA was reduced (P<0.05). The expressions of Prdx6 and GSH-Px1 were significantly increased (P<0.05，P<0.01), indicating that the SCL administration group was dose-dependent. Conclusion:SCL can improve the learning and memory ability of D-gal-induced aging mice, which may be related to the anti-oxidation ability of SCL and the up-regulation of Prdx6 and GSH-Px1 expressions in mouse brain tissue.