Approaching the intrinsic exciton physics limit in two-dimensional semiconductor diodes.

Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from their reduced dimensionality1-5. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are often plagued by many extrinsic factors, including chemical disorder at the semiconductor-contact interface. Here, by using van der Waals contacts with minimal interfacial disorder, we suppress contact-induced Shockley-Read-Hall recombination and realize nearly intrinsic photophysics-dictated device performance in 2D semiconductor diodes. Using an electrostatic field in a split-gate geometry to independently modulate electron and hole doping in tungsten diselenide diodes, we discover an unusual peak in the short-circuit photocurrent at low charge densities. Time-resolved photoluminescence reveals a substantial decrease of the exciton lifetime from around 800 picoseconds in the charge-neutral regime to around 50 picoseconds at high doping densities owing to increased exciton-charge Auger recombination. Taken together, we show that an exciton-diffusion-limited model well explains the charge-density-dependent short-circuit photocurrent, a result further confirmed by scanning photocurrent microscopy. We thus demonstrate the fundamental role of exciton diffusion and two-body exciton-charge Auger recombination in 2D devices and highlight that the intrinsic photophysics of 2D semiconductors can be used to create more efficient optoelectronic devices.

Enhancing Single Photon Emission Purity via Design of van der Waals Heterostructures.

Quantum emitters are essential components of quantum photonic circuitry envisioned beyond the current optoelectronic state-of-the-art. Two dimensional materials are attractive hosts for such emitters. However, the high single photon purity required is rarely realized due to the presence of spectrally degenerate classical light originating from defects. Here, we show that design of a van der Waals heterostructure effectively eliminates this spurious light, resulting in purities suitable for a variety of quantum technological applications. Single photon purity from emitters in monolayer WSe2 increases from 60% to 92% by incorporating this monolayer in a simple graphite/WSe2 heterostructure. Fast interlayer charge transfer quenches a broad photoluminescence background by preventing radiative recombination through long-lived defect bound exciton states. This approach is generally applicable to other 2D emitter materials, circumvents issues of material quality, and offers a path forward to achieve the ultrahigh single photon purities ultimately required for photon-based quantum technologies.

Approaching the Schottky-Mott limit in van der Waals metal-semiconductor junctions.

The junctions formed at the contact between metallic electrodes and semiconductor materials are crucial components of electronic and optoelectronic devices 1 . Metal-semiconductor junctions are characterized by an energy barrier known as the Schottky barrier, whose height can, in the ideal case, be predicted by the Schottky-Mott rule2-4 on the basis of the relative alignment of energy levels. Such ideal physics has rarely been experimentally realized, however, because of the inevitable chemical disorder and Fermi-level pinning at typical metal-semiconductor interfaces2,5-12. Here we report the creation of van der Waals metal-semiconductor junctions in which atomically flat metal thin films are laminated onto two-dimensional semiconductors without direct chemical bonding, creating an interface that is essentially free from chemical disorder and Fermi-level pinning. The Schottky barrier height, which approaches the Schottky-Mott limit, is dictated by the work function of the metal and is thus highly tunable. By transferring metal films (silver or platinum) with a work function that matches the conduction band or valence band edges of molybdenum sulfide, we achieve transistors with a two-terminal electron mobility at room temperature of 260 centimetres squared per volt per second and a hole mobility of 175 centimetres squared per volt per second. Furthermore, by using asymmetric contact pairs with different work functions, we demonstrate a silver/molybdenum sulfide/platinum photodiode with an open-circuit voltage of 1.02 volts. Our study not only experimentally validates the fundamental limit of ideal metal-semiconductor junctions but also defines a highly efficient and damage-free strategy for metal integration that could be used in high-performance electronics and optoelectronics.

The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers.

The prevalence of two major types of skin cancer, melanoma and non-melanoma skin cancer, has been increasing worldwide. Skin cancer incidence is estimated to rise continuously over the next 20 years due to ozone depletion and an increased life expectancy. Chemotherapeutic agents could affect healthy cells, and thus may be toxic to them and cause numerous side effects or drug resistance. Phytochemicals that are naturally occurring in fruits, plants, and herbs are known to possess various bioactive properties, including anticancer properties. Although the effects of phytochemicals are relatively milder than chemotherapeutic agents, the long-term intake of phytochemicals may be effective and safe in preventing tumor development in humans. Diverse phytochemicals have shown anti-tumorigenic activities for either melanoma or non-melanoma skin cancer. In this review, we focused on summarizing recent research findings of the natural and dietary terpenoids (eucalyptol, eugenol, geraniol, linalool, and ursolic acid) that have anticancer activities for both melanoma and non-melanoma skin cancers. These terpenoids may be helpful to protect skin collectively to prevent tumorigenesis of both melanoma and nonmelanoma skin cancers.

Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.

The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

Dural rupture and subsequent spinal cord herniation due to closed wound suction drainage after spinal surgery.

Closed wound suction drains are commonly used in spinal surgery. Severe neurological complications related to their use are rare. Here, we report a case of a dural rupture and subsequent spinal cord herniation related to the use of closed suction drains after posterior decompression and fixation surgery for spinal metastasis.

Role of Stem Cell-Derived Exosomes and microRNAs in Spinal Cord Injury.

Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways.

Large-Area Synthesis and Patterning of All-Inorganic Lead Halide Perovskite Thin Films and Heterostructures.

All-inorganic lead halide perovskites have attracted tremendous interest for their excellent stability when compared with hybrid perovskites. Here we report a large-area growth of monocrystalline all-inorganic perovskite thin films and further patterning them into heterostructure arrays. We show that highly oriented CsPbBr3 microcrystal domains can be readily grown on muscovite mica substrates with a well-defined epitaxial relationship, which can further expand and eventually merge into large-area monocrystalline CsPbBr3 thin films with an excellent optical quality. Taking a step further, we show the large-area CsPbBr3 thin film can be further patterned and selectively transformed into CsPbI3 using a selective anion-exchange process to produce CsPbBr3-CsPbI3 lateral heterostructure arrays with spatially modulated photoluminescence emission and an apparent current rectification behavior. The capability to grow large-area CsPbBr3 monocrystalline thin films and heterostructure arrays defines a robust material platform for both the fundamental investigations and potential applications in optoelectronics.

Effective connectivity alteration according to recurrence in transient global amnesia.

PURPOSE: This study aimed to evaluate alterations in structural covariance network and effective connectivity of the intrahippocampal circuit in patients with transient global amnesia (TGA). We also investigated whether there were differences of them according to recurrence. METHODS: We enrolled 88 patients with TGA and 50 healthy controls. We classified patients with TGA into two groups: the single event group (N = 77) and recurrent events group (N = 11). We performed volumetric analysis using the FreeSurfer program and structural covariance network analysis based on the structural volumes using a graph theoretical analysis in patients with TGA and healthy controls. The effective connectivity of the intrahippocampal circuit was also evaluated using structural equation modeling. RESULTS: There were no significant differences between patients with all TGA events/a single TGA event and healthy controls with regard to global structural covariance network. However, patients with recurrent events had significant alterations in global structural covariance network with a decrease in the small-worldness index (0.907 vs. 0.970, p = 0.032). In patients with all events/a single, there were alterations in effective connectivity from the entorhinal cortex to CA4, only. However, in patients with recurrent events, there were alterations in effective connectivity from the subiculum to the fimbria as well as from the entorhinal cortex to CA4 in bilateral hemispheres. CONCLUSION: Our study revealed significant alterations in structural covariance network and disruption of the intrahippocampal circuit in patients with TGA compared to healthy controls, which is more prominent when amnestic events recurred. It could be related to the pathogenesis of TGA.

Molecular Interaction Regulates the Performance and Longevity of Defect Passivation for Metal Halide Perovskite Solar Cells.

Defect passivation constitutes one of the most commonly used strategies to fabricate highly efficient perovskite solar cells (PSCs). However, the durability of the passivation effects under harsh operational conditions has not been extensively studied regardless of the weak and vulnerable secondary bonding between the molecular passivation agents and perovskite crystals. Here, we incorporated strategically designed passivating agents to investigate the effect of their interaction energies on the perovskite crystals and correlated these with the performance and longevity of the passivation effects. We unraveled that the passivation agents with a stronger interaction energy are advantageous not only for effective defect passivation but also to suppress defect migration. The prototypical PSCs treated with the optimal passivation agent exhibited superior performance and operational stability, retaining 81.9 and 85.3% of their initial performance under continuous illumination or nitrogen at 85 °C after 1008 h, respectively, while the reference device completely degraded during that time. This work provides important insights into designing operationally durable defect passivation agents for perovskite optoelectronic devices.

Unexpected abnormal intraoperative neurophysiologic monitoring change by multiple spontaneous intracerebral haemorrhage during endovascular coiling.

We report a patient with multiple angiographically negative intracerebral haemorrhages, which were recognized by significant changes in intraoperative neurophysiologic monitoring during the coil embolization of a left middle cerebral artery aneurysm.

Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases.

Aging gradually decreases cellular biological functions and increases the risk of age-related diseases. Cancer, type 2 diabetes mellitus, cardiovascular disease, and neurological disorders are commonly classified as age-related diseases that can affect the lifespan and health of individuals. Aging is a complicated and sophisticated biological process involving damage to biochemical macromolecules including DNA, proteins, and cellular organelles such as mitochondria. Aging causes multiple alterations in biological processes including energy metabolism and nutrient sensing, thus reducing cell proliferation and causing cellular senescence. Among the polyphenolic phytochemicals, resveratrol is believed to reduce the negative effects of the aging process through its multiple biological activities. Resveratrol increases the lifespan of several model organisms by regulating oxidative stress, energy metabolism, nutrient sensing, and epigenetics, primarily by activating sirtuin 1. This review summarizes the most important biological mechanisms of aging, and the ability of resveratrol to prevent age-related diseases.

Predictive value of neurophysiologic monitoring during neurovascular intervention for postoperative new neurologic deficits.

PURPOSE: Forms of intraoperative neurophysiologic monitoring (IONM), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), have been widely used in the field of neurosurgery. This study aimed to evaluate the diagnostic efficacy of IONM in identifying intraoperative events and predicting postoperative neurologic deficits in neurovascular intervention. METHODS: From January 2013 to December 2016, we retrospectively reviewed patients who underwent neurovascular intervention under general anesthesia with the use of IONM. Associations between significant changes in MEPs or SSEPs which were defined as a decrease more than 50% in amplitude and/or an increase more than 10% in latency and any identifiable intraoperative events and/or postoperative neurologic deficits were determined. The sensitivity and specificity values for both MEPs and SSEPs were calculated. RESULTS: In total, 578 patients (175 men and 403 women) were included. Their mean age was 59.5 years. SSEP changes occurred in 1% (n = 6), and MEP changes occurred in 1.2% (n = 7). Four patients suffered postoperative neurologic deficits, and identifiable intraoperative events were observed in seven patients. Both SSEP and MEP changes were significantly associated with identifiable intraoperative events and/or postoperative neurologic deficits (p < 0.001, Fisher's exact test). The calculated sensitivity and specificity of MEP monitoring were 50 and 99.5%, respectively. The sensitivity and specificity of SSEP monitoring were both 100%. CONCLUSION: Intraoperative SSEP monitoring might be a reliable and sensitive method to surveil neurologic complications during neurovascular intervention. Intraoperative MEP monitoring appears to be feasible. However, it is unclear whether MEP monitoring has any additive benefit over SSEP monitoring.

Angiographic and clinical outcomes of non-patent anastomosis after bypass surgery in adult moyamoya disease.

BACKGROUND: The clinical and radiologic outcomes of symptomatic adult moyamoya disease (MMD) patients who have an occluded anastomosis immediately after bypass surgery are poorly studied. The clinical and angiographic outcomes of non-patent anastomosis in symptomatic adult MMD patients were retrospectively reviewed. METHODS: From August 2011 to November 2016, 31 revascularization surgeries, consisting of direct and indirect bypass, were performed on 29 adult MMD patients. Primary outcomes were evaluated based on the frequency of transient ischaemic attack (TIA) incidence and the recurrence of cerebral infarction and were assessed as improvement or worsening. RESULTS: Among 31 cases, computed tomography angiography (CTA) on the first day after surgery showed patent anastomosis in 20 hemispheres and non-patent anastomosis in 11 hemispheres. Follow-up conventional angiographies showed spontaneous recanalization of non-patent anastomosis in all occlusion cases. The incidence of TIA decreased in both the non-patent and the patent groups. Two newly developed cerebral infarctions were observed, which occurred in the patent group. Patients in the non-patent group also showed clinical improvement after surgery (p = 0.04), and no significant relationship was found between immediate postoperative patency and the primary outcome (p = 0.53). CONCLUSIONS: In our series, regardless of patency immediately after bypass surgery, delayed recanalization and clinical improvement can be expected after bypass surgery for adult MMD.

Self-releasing of a titanium clamp (CranioFix) in cranioplasty.

The CranioFix® titanium clamp was developed for fixing bone flaps after craniotomy. In this case, to prevent cosmetic problems, the bone flaps were trimmed with a beveled edge, and a CranioFix clamp was used for bone flap fixation. As the brain swelled, the CranioFix clamp became loosened. If brain swelling is anticipated and bone margins have been trimmed, it may be better to consider other fixation methods.

Chicoric acid mitigates impaired insulin sensitivity by improving mitochondrial function.

Mitochondrial dysfunction is associated with insulin resistance. Although chicoric acid (CA) is known to have beneficial effects on insulin sensitivity, the involvement of mitochondrial function has not been elucidated yet. Here, we investigated the effect of CA on insulin resistance and mitochondrial dysfunction. In palmitate-induced insulin-resistant C2C12 myotubes, CA improved impaired glucose uptake and insulin signaling pathways, along with enhanced mitochondrial membrane potential and oxygen consumption. CA treatment in diet-induced obese mice ameliorated glucose tolerance and increased insulin sensitivity. CA treatment also recovered the dysregulated expression of glucose metabolism-related genes in the high-fat-fed mice. CA significantly increased the mitochondrial DNA content, citrate synthase, and ATP content, as well as the expression of genes related to mitochondrial biogenesis and oxidative phosphorylation in the liver and skeletal muscle in high-fat- fed obese mice. These findings suggested that CA attenuates insulin resistance and promotes insulin sensitivity by enhancing mitochondrial function.

Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid.

The mouse olfactory receptor Olfr544 is expressed in several non-olfactory tissues and has been suggested as a functional receptor regulating different signaling pathways. However, the molecular interaction between Olfr544 and its natural ligand, azelaic acid (AzA), remains poorly characterized, primarily due to difficulties in the heterologous expression of the receptor protein on the cell membrane and lack of entire protein structure. In this report, we describe the molecular determinants of Olfr544 activation by AzA. N-terminal lucy-flag-rho tag ensured the heterologous expression of Olfr544 on the Hana3A cell surface. Molecular modeling and docking combined with mutational analysis identified amino acid residues in the Olfr544 for the interaction with AzA. Our data demonstrated that the Y109 residue in transmembrane helix 3 forms a hydrogen bond with AzA, which is crucial for the receptor-ligand interaction and activation. Y109 is required for the Olfr544 activation by AzA which, in turn, stimulates the Olfr544-dependent CREB-PGC-1α signaling axis and is followed by the induction of mitochondrial biogenesis in Olfr544 wild-type transfected Hana3A cells, but not in mock or Y109A mutant transfected cells. Collectively, these data indicated that a hydrogen bond between Y109 residue and AzA is a major determinant of the Olfr544-AzA interaction and activation.

Fermented green tea extract exhibits hypolipidaemic effects through the inhibition of pancreatic lipase and promotion of energy expenditure.

Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.

Syringaresinol induces mitochondrial biogenesis through activation of PPARß pathway in skeletal muscle cells.

Activation of peroxisome proliferator-activated receptors (PPARs) plays a crucial role in cellular energy metabolism that directly impacts mitochondrial biogenesis. In this study, we demonstrate that syringaresinol, a pharmacological lignan extracted from Panax ginseng berry, moderately binds to and activates PPARß with KD and EC50 values of 27.62±15.76µM and 18.11±4.77µM, respectively. Subsequently, the expression of peroxisome proliferator-activated receptor γ coactivator-1α together with PPARß transcriptional targets, mitochondrial carnitine palmitoyltransferase 1 and uncoupling protein 2, was also enhanced in terms of both mRNA and protein levels. The activation of these proteins induced mitochondrial biogenesis by enrichment of mitochondrial replication and density within C2C12 myotubes. Importantly, knockdown of PPARß reduced the syringaresinol-induced protein expression followed by the significant reduction of mitochondrial biogenesis. Taken together, our results indicate that syringaresinol induces mitochondrial biogenesis by activating PPARß pathway.