Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed Analysis Through Literature Review.

OBJECTIVES: Deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied to clinic for approximately 30 years. The goal of this review is to explore the similarities and differences between "awake" and "asleep" DBS techniques. METHODS: A comprehensive literature review was carried out to identify relevant studies and review articles describing applications of "awake" or "asleep" DBS for Parkinson's disease. The surgical procedures, clinical outcomes, costs and complications of each technique were compared in detail through literature review. RESULTS: The surgical procedures of awake and asleep DBS surgeries rely upon different methods for verification of intended target acquisition. The existing research results demonstrated that the stereotactic targeting accuracy of lead placement obtained by either method is reliable. There were no significant differences in clinical outcomes, costs, or complications between the two techniques. CONCLUSION: The surgical and clinical outcomes of asleep DBS for PD are comparable to those of awake DBS.

Photooxidative Generation of Dodecaborate-Based Weakly Coordinating Anions.

Redox-active proanions of the type B12(OCH2Ar)12 [Ar = C6F5 (1), 4-CF3C6H4 (2), 3,5-(CF3)2C6H3 (3)] are introduced in the context of an experimental and computational study of the visible-light-initiated polymerization of a family of styrenes. Neutral, air-stable proanions 1-3 were found to initiate styrene polymerization through single-electron oxidation under blue-light irradiation, resulting in polymers with number-average molecular weights (Mn) ranging from ∼6 to 100 kDa. Shorter polymer products were observed in the majority of experiments, except in the case of monomers containing 4-X (X = F, Cl, Br) substituents on the styrene monomer when polymerized in the presence of 1 in CH2Cl2. Only under these specific conditions are longer polymers (>100 kDa) observed, strongly supporting the formulation that reaction conditions significantly modulate the degree of ion pairing between the dodecaborate anion and cationic chain end. This also suggests that 1-3 behave as weakly coordinating anions (WCA) upon one-electron reduction because no incorporation of the cluster-based photoinitiators is observed in the polymeric products analyzed. Overall, this work is a conceptual realization of a single reagent that can serve as a strong photooxidant, subsequently forming a WCA.

Key amino acid associated with acephate detoxification by Cydia pomonella carboxylesterase based on molecular dynamics with alanine scanning and site-directed mutagenesis.

Insecticide-detoxifying carboxylesterase (CE) gene CpCE-1 was cloned from Cydia pomonella. Molecular dynamics (MD) simulation and computational alanine scanning (CAS) indicate that Asn 232 in CpCE-1 constitutes an approximate binding hot-spot with a binding free energy difference (ΔΔGbind) value of 3.66 kcal/mol. The catalytic efficiency (kcat/km) of N232A declined dramatically, and the half inhibitory concentrations (IC50) value increased by more than 230-fold. Metabolism assay in vitro reveals that the acephate could be metabolized by wild CpCE-1, whereas N232A mutation is unable to metabolize the acephate, which suggests that the hot-spot Asn 232 is a crucial residue for acephate metabolism. Mutation detection suggests that low frequency of Asn 232 replacement occurred in Europe field strains. Our MD, CAS, site-directed mutagenesis, and metabolism studies introduce a new amino acid residue Asn 232 involved in the metabolism of the acephate with CpCE-1, and this method is reliable in insecticide resistance mechanism research and prediction of key amino acids in a protein which is associated with specific physiological and biochemical functions.

Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner.

Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST) and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9) as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

Angiogenesis-Related Gene Signature-Derived Risk Score for Glioblastoma: Prospects for Predicting Prognosis and Immune Heterogeneity in Glioblastoma.

Background: Glioblastoma multiforme (GBM) is the most common malignant tumor in the central nervous system with poor prognosis and unsatisfactory therapeutic efficacy. Considering the high correlation between tumors and angiogenesis, we attempted to construct a more effective model with angiogenesis-related genes (ARGs) to better predict therapeutic response and prognosis. Methods: The ARG datasets were downloaded from the NCBI-Gene and Molecular Signatures Database. The gene expression data and clinical information were obtained from TCGA and CGGA databases. The differentially expressed angiogenesis-related genes (DE-ARGs) were screened with the R package "DESeq2". Univariate Cox proportional hazards regression analysis was used to screen for ARGs related to overall survival. The redundant ARGs were removed by least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the gene signature of DE-ARGs, a risk score model was established, and its effectiveness was estimated through Kaplan-Meier analysis, ROC analysis, etc. Results: A total of 626 DE-ARGs were explored between GBM and normal samples; 31 genes were identified as key DE-ARGs. Then, the risk score of ARG signature was established. Patients with high-risk score had poor survival outcomes. It was proved that the risk score could predict some medical treatments' response, such as temozolomide chemotherapy, radiotherapy, and immunotherapy. Besides, the risk score could serve as a promising prognostic predictor. Three key prognostic genes (PLAUR, ITGA5, and FMOD) were selected and further discussed. Conclusion: The angiogenesis-related gene signature-derived risk score is a promising predictor of prognosis and treatment response in GBM and will help in making appropriate therapeutic strategies.

Glutathione S-Transferase Genes are Involved in Lambda-Cyhalothrin Resistance in Cydia pomonella via Sequestration.

Pest management is mostly accomplished by the use of insecticides. However, the overuse of insecticides has led to the development of resistance. Glutathione S-transferases (GSTs) are vital detoxification enzymes involved in insecticide resistance in insects. In this study, we report the involvement of GSTs in insecticide resistance to lambda-cyhalothrin in Cydia pomonella, a globally quarantined fruit pest. A total of 25 GST, including 22 cytosolic genes and 3 microsomal genes, are identified from the genome database of C. pomonella. These cytosolic genes are further classified into six classes, including four in delta, eight in epsilon, three in omega, three in sigma, one in theta, and one in zeta class, as well as two unclassified genes. The real-time quantitative polymerase chain reaction (RT-qPCR) shows that the majority of these genes are mainly expressed throughout the larval stage and in the midgut of the fourth-instar larvae. Exposure to an LD10 dose of lambda-cyhalothrin resulted in the upregulation of 17 GST genes. Moreover, mRNA levels of most GST genes, with the exception of CpGSTe6, CpGSTd2, CpGSTd4, and CpGSTz1, are considerably higher in a lambda-cyhalothrin-resistant population (ZW_R) than those of susceptible strains. Recombinant CpGSTd1, CpGSTd3, CpGSTe3, and CpGSTs2 can bind and metabolize lambda-cyhalothrin, with the highest metabolic rate observed for CpGSTd3 but no metabolite(s) was detected, supporting the role of GSTs in sequestration of lambda-cyhalothrin. Molecular dynamics simulation analysis indicates that key residues of hydrophobic pocket-derived lipophilic energy S(lipo) interactions with a hydrophobic pharmacophore of lambda-cyhalothrin are crucial for metabolism by CpGSTd3 and further lead to resistance. Our study is the first to experimentally confirm the involvement of GSTs in lambda-cyhalothrin resistance via sequestration and provides new insights into resistance management in C. pomonella.

The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing.

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws.

The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.

Local anesthesia in oral and maxillofacial surgery: A review of current opinion.

Local anesthesia (LA) is the most important pain management process in oral and maxillofacial surgery. Safe and effective LA not only enable patients to obtain high-quality treatment, but also relieve the anxiety of patients when they come to the clinic. The choices of local anesthetic and injection methods determine the success of LA to a great extent. At present, in most countries or regions, common local anesthetics used in oral and maxillofacial surgery belong to amides and they are injected into patients' body mainly through block or infiltration anesthesia. In addition, the operators' technique level, patient's subjective psychology and anatomical variation of maxillofacial structure also have a strong influence on LA in dental clinic. Due to the existence of above factors, the worldwide success rates of LA in oral and maxillofacial surgery is very different. There are no specific LA methods that ensure 100% successful LA rates. Fortunately, the development of new local anesthetic and injection technology are providing us with new ideas to solve this problem. This review mainly report the new research progress on LA in oral and maxillofacial surgery in recent decades and help clinicians with dental LA operation.

Distal-triangular flap design for impacted mandibular third molars: a randomized controlled trial.

OBJECTIVES: This prospective study was performed to evaluate whether the distal-triangular flap was a practical alternative surgical approach for extracting mandibular third molars. METHODS: Sixty participants with impacted mandibular third molars were randomly divided into three groups: group A, distal-triangular flap; group B, Szmyd flap; and group C, envelope flap. The impacted third molars were extracted by the corresponding flapping method. During a three-month follow-up observation after the extraction, the postoperative pain, swelling, mouth opening, and periodontal status were recorded and analyzed by ANOVA and chi-square tests. RESULTS: The 60 participants had successful extraction and 3-month follow-up observation. No participant suffered from postoperative infections, lower lip disorder, or tongue sensory disorders. No statistical differences were found in the postoperative symptoms and signs of the three flap designs, such as postoperative pain, swelling, mouth opening, and periodontal status (P>0.05). CONCLUSIONS: The distal-triangular flap was as safe and reliable as the Szmyd and envelope flaps but more advantageous because of its convenient operative field exposure and low requirement for the patient's mouth opening. Thus, the distal-triangular flap is one of the alternative flap options for extracting impacted mandibular third molars.

[Clinical study of age-related sensory innervation of the anterior hard palate].

OBJECTIVES: The present study aimed to explore the innervation of the anterior hard palatine and its relationship with individual development stage. Specifically, the effects of anesthesia on patients of different ages were observed, and neurodevelopment in the maxillofacial region was invesitgated. References that are helpful in selecting local anesthesia were provided. METHODS: A total of 182 patients with mixed dentition were randomly divided into the nasopalatine nerve block and greater palatine nerve block groups. Then, 219 patients with permanent dentition were divided into an adolescent group (13-18 years old) and adult group (over 19 years old), all of whom underwent bilateral greater palatine nerve block. Palatal mucosal pain sensation was tested pre- and post-anesthesia with Von Frey hairs. RESULTS: Among the children with mixed dentition, bilateral greater palatine nerve block tended to result in better anesthetic effects than nasopalatine nerve block (P<0.05), except in the incisive papilla. No difference in anesthetic effect was observed between adolescents and adults (P>0.05). The bilateral greater palatine nerve block was more effective in inducing an anesthestic effect in the anterior hard palatine in mixed dentition than in permanent dentition (over 13 years old; P<0.05). CONCLUSIONS: The sensation of the anterior hard palatine seems mainly dominated by the greater palatine nerve until mixed dentition and gradually shifted to the nasopalatine nerve in conjunction with maxillary development and tooth replacement. Hence, the innervation of the anterior hard palatine induce a secondary development during the development of the maxilla.

Assessment of effects of climate change and grazing activity on grassland yield in the Three Rivers Headwaters Region of Qinghai-Tibet Plateau, China.

Inter-annual dynamics of grassland yield of the Three Rivers Headwaters Region of Qinghai-Tibet Plateau of China in 1988-2005 was analyzed using the GLO-PEM model, and the herbage supply function was evaluated. The results indicate that while grassland yield in the region showed marked inter-annual fluctuation there was a trend of increased yield over the 18 years of the study. This increase was especially marked for Alpine Desert and Alpine Steppe and in the west of the region. The inter-annual coefficient of variation of productivity increased from the east to the west of the region and from Marsh, Alpine Meadow, Alpine Steppe, Temperate Steppe to Alpine Desert grasslands. Climate change, particularly increased temperatures in the region during the study period, is suggested to be the main cause of increased grassland yield. However, reduced grazing pressure and changes to the seasonal pattern of grazing could also have influenced the grassland yield trend. These findings indicate the importance of understanding the function of the grassland ecosystems in the region and the effect of climate change on them especially in regard to their use to supply forage for animal production. Reduction of grazing pressure, especially during winter, is indicated to be critical for the restoration and sustainable use of grassland ecosystems in the region.

The application of bone marrow mesenchymal stem cells and biomaterials in skeletal muscle regeneration.

Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells in vivo. The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.

Basal forebrain GABAergic neurons promote arousal and predatory hunting.

Predatory hunting is an important approach for animals to obtain valuable nutrition and energy, which critically depends on heightened arousal. Yet the neural substrates underlying predatory hunting remain largely undefined. Here, we report that basal forebrain (BF) GABAergic neurons play an important role in regulating predatory hunting. Our results showed that BF GABAergic neurons were activated during the prey (cricket)-hunting and food feeding in mice. Optogenetic activation of BF GABAergic neurons evoked immediate predatory-like actions to both artificial and natural preys, significantly reducing the attack latency while increasing the attack probability and the number of killed natural prey (crickets). Similar to the effect of activating the soma of BF GABAergic neurons, photoactivation of their terminals in the ventral tegmental area (VTA) also strongly promotes predatory hunting. Moreover, photoactivation of GABAergic BF - VTA pathway significantly increases the intake of various food in mice. By synchronous recording of electroencephalogram and electromyogram, we showed that photoactivation of GABAergic BF - VTA pathway induces instant arousal and maintains long-term wakefulness. In summary, our results clearly demonstrated that the GABAergic BF is a key neural substrate for predatory hunting, and promotes this behavior through GABAergic BF - VTA pathway.

Glutamatergic lateral hypothalamus promotes defensive behaviors.

The glutamatergic lateral hypothalamus (LH) has been implicated in a variety of behaviors, such as evasion and feeding, while its role in defensive behaviors and relevant neurocircuits remains unclear. Here, we demonstrated that the glutamatergic LH is a critical structure regulating defensive behaviors. Trimethylthiazole (TMT), the odor of mice predator, significantly increased c-Fos expression in the LH. Using fiber photometry technology, we found that TMT exposure increased the activity of LH glutamatergic neurons. Selective activation of LH glutamatergic neurons with optogenetics and chemogenetics promoted a series of defense-related behaviors, including fleeing, avoidance, and hiding, while selective inhibition of LH glutamatergic neurons suppressed the avoidance provoked by TMT. Activation of both the glutamatergic LH terminals in the hypothalamic paraventricular nucleus (PVN) and the glutamatergic projection from the basolateral amygdala (BLA) to the LH elicited defensive behaviors. Finally, by combining the viral-mediated retrograde tracing with anterograde activation, we found that PVN-projecting glutamatergic neurons in the LH were activated by BLA glutamatergic inputs. Taken together, our results illustrate that the glutamatergic LH is a pivotal relay of defensive behaviors and possibly promotes these behaviors through the BLA→LH→PVN pathway.

Adipose Stem Cell-Based Clinical Strategy for Neural Regeneration: A Review of Current Opinion.

Nerve injury is a critical problem in the clinic. Nerve injury causes serious clinic issues including pain and dysfunctions for patients. The disconnection between damaged neural fibers and muscles will result in muscle atrophy in a few weeks if no treatment is applied. Moreover, scientists have discovered that nerve injury can affect the osteogenic differentiation of skeletal stem cells (SSCs) and the fracture repairing. In plastic surgery, muscle atrophy and bone fracture after nerve injury have plagued clinicians for many years. How to promote neural regeneration is the core issue of research in the recent years. Without obvious effects of traditional neurosurgical treatments, research on stem cells in the past 10 years has provided a new therapeutic strategy for us to address this problem. Adipose stem cells (ASCs) are a kind of mesenchymal stem cells that have differentiation potential in adipose tissue. In the recent years, ASCs have become the focus of regenerative medicine. They play a pivotal role in tissue regeneration engineering. As a type of stem cell, ASCs are becoming popular for neuroregenerative medicine due to their advantages and characteristics. In the various diseases of the nervous system, ASCs are gradually applied to treat the related diseases. This review article focuses on the mechanism and clinical application of ASCs in nerve regeneration as well as the related research on ASCs over the past decades.

Dodecaborane-Based Dopants Designed to Shield Anion Electrostatics Lead to Increased Carrier Mobility in a Doped Conjugated Polymer.

One of the most effective ways to tune the electronic properties of conjugated polymers is to dope them with small-molecule oxidizing agents, creating holes on the polymer and molecular anions. Undesirably, strong electrostatic attraction from the anions of most dopants localizes the holes created on the polymer, reducing their mobility. Here, a new strategy utilizing a substituted boron cluster as a molecular dopant for conjugated polymers is employed. By designing the cluster to have a high redox potential and steric protection of the core-localized electron density, highly delocalized polarons with mobilities equivalent to films doped with no anions present are obtained. AC Hall effect measurements show that P3HT films doped with these boron clusters have conductivities and polaron mobilities roughly an order of magnitude higher than films doped with F4 TCNQ, even though the boron-cluster-doped films have poor crystallinity. Moreover, the number of free carriers approximately matches the number of boron clusters, yielding a doping efficiency of ≈100%. These results suggest that shielding the polaron from the anion is a critically important aspect for producing high carrier mobility, and that the high polymer crystallinity required with dopants such as F4 TCNQ is primarily to keep the counterions far from the polymer backbone.

[Progress on medication-related osteonecrosis of the jaw].

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.