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Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1–4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI. [ABSTRACT FROM AUTHOR]

Groundwater resources are required for domestic water supply, agriculture, and industry, and the strategic importance of water resources will only increase in the context of climate change and population growth. For optimal management of this crucial resource, exploration of the potential of groundwater is necessary. To this end, the objective of this study was the development of a new method based on remote sensing, deep neural networks (DNNs), and the optimization algorithms Adam, Flower Pollination Algorithm (FPA), Artificial Ecosystem-based Optimization (AEO), Pathfinder Algorithm (PFA), African Vultures Optimization Algorithm (AVOA), and Whale Optimization Algorithm (WOA) to predict groundwater potential in the North Central region of Vietnam. 95 springs or wells with 13 conditioning factors were used as input data to the machine learning model to find the statistical relationships between the presence and nonpresence of groundwater and the conditioning factors. Statistical indices, namely root mean square error (RMSE), area under curve (AUC), accuracy, kappa (K) and coefficient of determination (R2), were used to validate the models. The results indicated that all the proposed models were effective in predicting groundwater potential, with AUC values of more than 0.95. Among the proposed models, the DNN-AVOA model was more effective than the other models, with an AUC value of 0.97 and an RMSE of 0.22. This was followed by DNN-PFA (AUC=0.97, RMSE=0.22), DNN-FPA (AUC=0.97, RMSE=0.24), DNN-AEO (AUC=0.96, RMSE=0.25), DNN-Adam (AUC=0.97, RMSE=0.28), and DNN-WOA (AUC=0.95, RMSE=0.3). In addition, according to the groundwater potential map, about 25–30% of the region was in the high and very high potential groundwater zone; 5–10% was in the moderate zone, and 60–70% was low or very low. The results of this study can be used in the management of water resources in general and the location of appropriate wells in particular. [ABSTRACT FROM AUTHOR]

Objective: To explore and analyze the clinical efficacy of a stepwise decompression technique in the treatment of trigeminal neuralgia (TN) caused by vertebrobasilar dolichoectasia (VBD). Methods: A total of 918 patients with TN admitted to our hospital from June 2015 to May 2020 were divided into the VBD group (n = 61) and the conventional group (n = 857). The VBD group underwent stepwise decompression, while the conventional group received traditional microvascular decompression (MVD) surgery. Patients associated with the VBD were divided into direct compression (n = 14) and indirect compression group (n = 47) who had compression by other vessels in the presence of the VBD. Thereafter, the clinical data, intraoperative findings, efficacy, and complications were analyzed. Results: The curative ratio, efficacy, and recurrence rate for the VBD and conventional group were 83.6% and 89.6%, 93.4% and 95.3%, and 8.2% and 5.3%, respectively. The curative ratio, efficacy, and recurrence rate for the direct compression and indirect compression group were 85.7% and 83.0%, 92.9% and 93.6%, and 7.1% and 8.5%, separately. There were no significant differences in the curative ratio, efficacy, recurrence rate, and the incidence of complications between the two series (P > 0.05). Conclusion: For TN caused by VBD, stepwise decompression not only reduces the direct compression of the trigeminal nerve by VBA but also allows identification and decompression of the actual vessels responsible for the compression. It has a good curative ratio, efficacy, and long-term pain relief rate, and it does not significantly increase the incidences of complications after surgery. [ABSTRACT FROM AUTHOR]

Synergistic effects between hard carbons and soft carbons are proven to be helpful for improving the electrochemical performance of carbonaceous anode for potassium-ion batteries (PIBs). However, the phase separation of precursors limits the synergistic effects and improvement of electrochemical performance. Here, inspired by the esterification reaction, the precursors of two sorts of carbon are connected at the molecular level, which boosts the synergistic effects in hybrid carbon, resulting in excellent electrochemical kinetics and low charge/discharge voltage. Consequently, the hybrid carbon anode exhibited a high specific capacity of 121 mAh·g−1 at 3.2 A·g−1, a high-rate capability, and stable cycling performance. After 500 cycles at 1 A·g−1, the average capacity fading is only 0.078% per cycle. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to combine voxel-based morphometry, deformation-based morphometry, and surface-based morphometry to analyze gray matter volume and cortex shape in classical trigeminal neuralgia patients. Methods: This study included 79 classical trigeminal neuralgia patients and age- and sex-matched 81 healthy controls. The aforementioned three methods were used to analyze brain structure in classical trigeminal neuralgia patients. Spearman correlation analysis was used to analyze the correlation of brain structure with the trigeminal nerve and clinical parameters. Results: The bilateral trigeminal nerve was atrophied, and the ipsilateral trigeminal nerve volume was smaller than the contralateral volume in the classical trigeminal neuralgia. The gray matter volume of Temporal_Pole_Sup_R and Precentral_R was found to be decreased using voxel-based morphometry. The gray matter volume of Temporal_Pole_Sup_R had a positive correlation with disease duration and a negative correlation with the cross-section area of the compression point and the quality-of-life score in trigeminal neuralgia. The gray matter volume of Precentral_R was negatively correlated with the ipsilateral volume of the trigeminal nerve cisternal segment, cross-section area of compression point, and visual analogue scale. The gray matter volume of Temporal_Pole_Sup_L was found to be increased using deformation-based morphometry and had a negative correlation with the self-rating anxiety scale. The gyrification of the middle temporal gyrus_L increased and the Postcentral_L thickness decreased, as detected using surface-based morphometry. Conclusions: The gray matter volume and cortical morphology of pain-related brain regions were correlated with clinical and trigeminal nerve parameters. voxel-based morphometry, deformation-based morphometry, and surface-based morphometry complemented each other in analyzing the brain structures of patients with classical trigeminal neuralgia and provided a basis for studying the pathophysiology of classical trigeminal neuralgia. Highlights: We first applied the three methods (VBM, DBM, and SBM) to the brain structure study in CTN and found that the three methods were complementary. Some of the different brain regions correlated with clinical parameters, TGNcV, and CSA of the compression point. [ABSTRACT FROM AUTHOR]

Seagrasses are among the most important ecosystems of continental and island coastal waters globally. Analyses of the species diversity, structure, and distribution mapping of seagrass communities provide a scientific basis for seagrass conservation and development and protection of the marine environment. The application of remote sensing, especially using very high-resolution remote sensing data, in mapping seagrass distribution confers high accuracy and detailed results. The distribution of seagrass communities and benthic biomes typical of Nam Yet Island, Truong Sa Archipelago, Vietnam was mapped using object-based classification of Pléiades satellite imagery with four spectral bands (red, blue, green, and near-infrared) and the Green–Blue Normalized Difference Vegetation Index, combined with handheld positioning devices (total field samples 100, overall accuracy 91%, kappa coefficient = 0.88). Besides, by sampling and measurement in the field, two seagrass species, Thalassia hemprichii and Halophila ovalis were identified with the same structure, density, and biomass in the northern and southern parts of the island. The application of high-resolution remote sensing images combined with field surveys contributes to improving the accuracy of seagrass distribution maps as well as benthic biome ones for shallow sea areas. Establishing a seagrass distribution map and assessing the diversity of seagrass is the basis for the conservation and development of the current seagrass community at Nam Yet Island. [ABSTRACT FROM AUTHOR]

The structures and energetics of the binuclear cyclobutadiene vanadium carbonyls (C4H4)2V2(CO)n (n = 8, 7, 6, 5, 4, 3, 2) have been investigated by density functional theory (DFT). The lowest energy (C4H4)2V2(CO)8 structure consists of two C4H4V(CO)4 units linked by a V-V single bond of length 3.4 Å. The two lowest energy (C4H4)2V2(CO)7 structures also have formal V-V single bonds. The "extra" two electrons to give each vanadium atom in these heptacarbonyls the favored 18-electron configuration can come from either an agostic C-H-V interaction activating a hydrogen atom from one of the cyclobutadiene rings or from a four-electron donor bridging η2-µ-CO group with a short V–O distance. The lowest energy (C4H4)2V2(CO)6 structure has a formal V≡V triple bond of length 2.52 Å similar to the V≡V triple bond of length 2.46 Å found in the experimentally known cyclopentadienyl derivative (η5-C5H5)2V2(CO)5. The lowest energy structures for the more highly unsaturated (C4H4)2V2(CO)n (n = 5, 4, 3, 2) have at least two four-electron donor bridging η2-µ-CO groups and a vanadium-vanadium bond order sufficient to give each vanadium atom at least a 16-electron configuration. The structures and energetics of the binuclear cyclobutadiene vanadium carbonyls (C4H4)2V2(CO)n (n = 8, 7, 6, 5, 4, 3, 2) have been investigated by density functional theory. The two lowest energy (C4H4)2V2(CO)7 structures include one with an agostic C-H-V interaction activating a hydrogen atom from one of the cyclobutadiene rings and another with a four-electron donor bridging η2-µ-CO group with a short V–O bonding distance. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) is a severe neurological emergency, resulting in cognitive impairments and threatening human's health. Currently, SAH has no effective treatment. It is urgent to search for an effective therapy for SAH. Objective: To explore the expression of Omi protein after subarachnoid hemorrhage in rats. Methods: SAH rat model was established by injecting blood into the prechiasmatic cistern. Neurological deficit was assessed by detecting neurological deficit scores and brain tissue water contents. Apoptotic cells were evaluated by TUNEL staining and IHC staining. Omi and Cleaved caspase 3 expressions in nerve cells were determined by double staining using IF. Apoptosis-related proteins were measured by Western blotting assay. Results: SAH rat model was successfully established, showing more apoptotic cells and high neurological deficit scores in SAH rat. In SAH rat model, Omi expression in nerve cells was elevated and the upregulation of Omi mainly occurred in cytoplasm, accompanied by the degradation of XIAP and the increased cleaved caspase 3/9 and cleaved PARP. Once treated with UCF-101, a specific inhibitor of Omi, the increased cell apoptosis, left/right brain moisture contents and neurological deficits were notably reversed in SAH rat brain. Of note, SAH-induced the increases of apoptosis-related protein in nerve cells were also rescued by the administration of UCF-101. Conclusions: UCF-101-mediated Omi inhibition decreased the degradation of XIAP and subsequently inhibited the activation of apoptosis-related proteins, decreased nerve cell apoptosis, leading to the improvement on early brain injury in SAH rat. UCF-101-based Omi inhibition may be used to treat SAH with great potential application. [ABSTRACT FROM AUTHOR]

The structures and energetics of the binuclear phospholyl vanadium carbonyls (C4H4P)2V2(CO)n (n = 7, 6, 5, 4, 3, 2, 1) have been investigated using density functional theory. The lowest energy heptacarbonyl (C4H4P)2V2(CO)7 structures resemble those of the dimanganese pentacarbonyl (C4H4P)2Mn2(CO)5 with one seven-electron donor bridging η5,η1-C4H4P ring and no direct vanadium–vanadium bond. Similarly, the lowest energy hexacarbonyl (C4H4P)2V2(CO)6 structure resembles that of the dimanganese tetracarbonyl (C4H4P)2Mn2(CO)4 with two seven-electron donor bridging η5,η1-C4H4P rings and no direct vanadium–vanadium bond. The lowest energy pentacarbonyl (C4H4P)2V2(CO)5 structure has terminal η5-C4H4P phospholyl rings and a formal V≡V triple bond of length ~ 2.45 Å similar to the experimentally known and structurally characterized cyclopentadienyl analogue (η5-C5H5)2V2(CO)5. Various combinations of V=V double bonds or V≡V triple bonds, four-electron donor bridging carbonyl groups and seven-electron donor bridging η5,η1-C4H4P rings are found in the more highly unsaturated derivatives (C4H4P)2V2(CO)n (n = 4, 3, 2) to give 17- and 18-electron vanadium configurations for triplet- and singlet-state structures, respectively. Formal V≣V quadruple bonds are found only in the highly unsaturated lowest energy singlet (C4H4P)2V2(CO)n (n = 2, 1) structures, which, however, lie at somewhat higher energies than isomeric triplet structures. [ABSTRACT FROM AUTHOR]

As one of the most abundant DNA methylation form in prokaryotes, N6-methyladenine nucleotide (6 mA) was however only recently identified in eukaryotic genomes. To explore the implications of N6-adenine methylation in adipogenesis, genomic N6-adenine methylation was examined across adipocyte differentiation stages of 3T3-L1 cells. When the N6-adenine methylation profiles were analyzed and compared with the levels of gene expression, a positive correlation between the density of promoter 6 mA and gene expression level was uncovered. By means of in vitro methylation and gene knockdown assay, METTL4, a homologue of Drosophila methylase CG14906 and C. elegans methylase DAMT-1, was demonstrated to be a mammalian N6-adenine methylase that functions in adipogenesis. Knockdown of Mettl4 led to altered adipocyte differentiation, shown by defective gene regulation and impaired lipid production. We also found that the effects of N6-adenine methylation on lipid production involved the regulation of INSR signaling pathway, which promotes glucose up-taking and lipid production in the terminal differentiation stage. [ABSTRACT FROM AUTHOR]

To explore the editing specificity of CRISPR/Cpf1 system, effects of target mutation were systematically examined using a reporter activation assay, with a set of single-nucleotide mutated target site. Consistent with our previous study performed with CRISPR/Cas9, a "core" sequence region that is highly sensitive to target mutation was characterized. The region is of 4-nucleotide long, located from +4 to +7 position of the target site, and positioned within a positively charged central channel when assembled into Cpf1 endonuclease. Single-nucleotide mutation at the core sequence could abolish gene editing mediated by a however active sgRNA. With a great majority of the target sites, a kind of 'super' off-target gene editing was observed with both CRISPR/Cpf1 and CRISPR/Cas9. For a given target site, mutation at certain positions led to greatly enhanced off-target gene editing efficacy, even up to 10-fold of that of the fully-matched target. Study further found that these effects were determined by the identity of target nucleotide, rather than the nucleotide of crRNA. This likely suggests that the interactions between target nucleotide and the endonuclease are involved in this process. [ABSTRACT FROM AUTHOR]

Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies [1]. Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus [2] and HIV [3], [4]. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins [3], [4]. Here we demonstrate that viperin catalyses the conversion of cytidine triphosphate (CTP) to 3ʹ-deoxy-3′,4ʹ-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. We show that mammalian cells expressing viperin and macrophages stimulated with IFNα produce substantial quantities of ddhCTP. We also establish that ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple members of the Flavivirus genus, and show that ddhCTP directly inhibits replication of Zika virus in vivo. These findings suggest a partially unifying mechanism for the broad antiviral effects of viperin that is based on the intrinsic enzymatic properties of the protein and involves the generation of a naturally occurring replication-chain terminator encoded by mammalian genomes. Viperin inhibits the replication of various viruses by catalysing the conversion of CTP to ddhCTP, which is a unique nucleotide that functions as replication-chain terminator of RNA-dependent RNA polymerases. [ABSTRACT FROM AUTHOR]

Using two series of de novo designed antimicrobial peptides, we studied the effects of peptide length and hydrophobicity/charge (H/C) ratio on the antimicrobial activities. For these peptides, a correlation was established between their antimicrobial efficacy and the leakage, aggregation, and fusion activities on artificial membrane. The results showed that peptides with an H/C ratio of 1.3, and a length of about half of the membrane thickness caused most potent membrane leakage, and negligible membrane aggregation and fusion. In addition, such peptide also exhibited the highest antimicrobial activity. Analysis of the hydrophobic and electrostatic interactions showed that the strength, the order and the position of these interactions determined the activities of the peptides on the artificial membrane and thus the antimicrobial efficacy. Further analyses on the tilt angle of the peptides on the membrane surface indicated that the peptides distorted the membrane in a dynamic mode, instead of being fixed in the membrane at a constant angle. [ABSTRACT FROM AUTHOR]

The authors describe a case of a purely primary extramedullary spinal germinoma in a young Chinese male. Primary spinal germinoma is extremely rare tumor. Currently, less than 30 histologically verified spinal germinoma cases have been reported previously, mostly involving Asian of Japanese descent. This 24-year-old male suffered from progressive low back pain radiating to both legs. Magnetic resonance imaging showed a well-demarcated, intradural extramedullary mass at the level of L2 and L3. The lesion was totally removed and was confirmed as a germinoma. Upon histological verification of the tumor, he was treated successfully with radiotherapy and adjuvant chemotherapy. This report also reviews the literature pertaining to primary spinal germinoma. Except for 16 cases with intramedullary lesions and five cases with both intra- and extramedullary tumors, there were only three previously reported cases of extramedullary spinal germinomas, all initially presenting with sausage-like lesions. To the authors' knowledge, it is thought to be the first case of such a tumor, roughly round in shape and extramedullary location. Although rare, primary spinal germinoma do occur and should be included in the differential diagnosis of spinal tumors. Aggressive malignant behavior has been reported and close follow-up is necessary. [ABSTRACT FROM AUTHOR]

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Background: Traditional endoscopic thoracic sympathicotomy is usually performed through an axillary incision with 5-mm thoracoscope under general anesthesia with endotrachea intubation. Nonintubated transareolar single-port thoracic sympathicotomy with a needle scope has rarely been attempted. The objective of this study is to evaluate the feasibility and safety of this minimally invasive technique in managing primary palmar hyperhidrosis (PPH).Methods: From May 2012 to May 2014, a total of 85 male patients with severe PPH underwent transareolar single-port thoracic sympathicotomy by use of a 2-mm needle scope under total intravenous anesthesia without endotrachea intubation.Results: All procedures were successfully performed with a mean operating time of 13.5 min. The palms of all patients became dry and warm as soon as the sympathetic chain was cut off. There were no sore throat, and all the patients regained consciousness rapidly after surgery. Eighty-two patients (96.5 %) were discharged from the hospital on the first postoperative day. The postoperative complications were minor, and no patients developed Horner's syndrome. At 6 months postoperatively, there is no obvious surgical scar on the chest wall, and none of the patients complained about postoperative pain. Compensatory sweating appeared in 31 patients. No recurrent symptoms were observed in our study. One-year follow-up revealed an excellent cosmetic result and degree of satisfaction.Conclusions: Nonintubated transareolar single-port needlescopic thoracic sympathicotomy is a safe, effective and minimally invasive therapeutic procedure, which can be performed in routine clinical practice for male PPH patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP).Methods: This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter.Results: The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay.Conclusion: Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach. [ABSTRACT FROM AUTHOR]

MicroRNAs are short endogenous non-coding RNAs that regulate gene expression in various physiological and pathological conditions. To characterize autoantigen-targeting microRNAs in Sjögren's syndrome (SS), a systematic study was carried out, in which a candidate microRNA set was first identified by bioinformatics analysis and literature search. Then, their gene silencing activities were evaluated with fusion reporter gene and endogenous targets, leading to the identification of three microRNAs: TRIM21-targeting miR-1207-5p, TRIM21-targeting miR-4695-3p, and La autoantigen-targeting miR-299-5p. Compared to healthy controls, downregulation of miR-1207-5p and miR-4695-3p expression was further revealed in the minor salivary glands of primary SS (pSS) patients. This, on the one hand, characterized two autoantigen-targeting microRNAs in Sjögren's syndrome and, on the other hand, suggested that downregulation of miR-1207-5p and miR-4695-3p expression may lead to increased TRIM21 levels in the minor salivary glands, which contributes to the development of Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

In this paper, a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy. The conjugation of peptides at either 3′-terminus of siCdc2 bring no change to the classical A-form of RNA duplex, but slightly compromise the thermodynamic stability. Peptide conjugation at the 3′-terminus of sense strand could improve the serum stability obviously, however, the opposite peptide conjugation at the 3′-terminus of antisense strand shows no such influence. According to the results of artificial silencing activity assay system, peptide conjugation at 3′-terminus of antisense strand slightly weakens the silencing activity of siCdc2. But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2, meanwhile, it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA. [ABSTRACT FROM AUTHOR]

Background: Due to its anatomical features, the vertebrobasilar artery complex (VBA) seldom contributes to the neurovascular conflict in patient with trigeminal neuralgia (TN). However, once it offends the trigeminal root, this large artery is really difficult to manipulate during microvascular decompression (MVD) surgery. Therefore, the surgical strategy for such cases needs to be detailed in order to obtain a satisfactory outcome. Methods: From 2009 through 2011, 475 consecutive TN patients underwent MVDs in our department. Among them, ten were found in which an ipsilateral deviating ectatic vertebrobasilar artery complex (VBA) offended the trigeminal nerve. Those cases were focused on in this study and each operation was analyzed retrospectively. Results: During the operation, the vertebral artery was regarded as the direct culprit in six (60 %) patients, while the basilar artery in four (40 %). As companions, some smaller vessels were also observed to be close to the nerve, including the superior cerebellar artery (SCA) in five, veins in two and anterior inferior cerebellar artery (AICA) in two. The neurovascular conflict was discovered in the cisternal segment of the trigeminal root in eight, while in the root entry zone (REZ) in two. In six out of the ten cases, the affected nerves were demonstrated to be squeezed towards the tentorium by the ectatic VBA. Postoperatively, the symptom of pain totally disappeared immediately in eight (80 %) patients, while it was relieved apparently in two (20 %). During the follow-up period of 3-30 months, no recurrence or complication was found, except for one patient who had numbness of the face. Conclusion: With a proper strategy, MVD is probably the most effective therapy for the TN cases caused by ectatic vertebrobasilar artery complex. The substance of the surgery is to withdraw the proximal vertebral artery caudally via a lateroinferior cerebellar approach. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Change history: In the HTML version of this Letter, Extended Data Fig. 4 incorrectly corresponded to Fig. 4 (the PDF version of the figure was correct). This has been corrected online. [ABSTRACT FROM AUTHOR]

Targeting specificity is an essential issue in the development of CRISPR-Cas technology. Using a luciferase activation assay, off-target cleavage activity of sgRNA was systematically investigated on single nucleotide-mismatched targets. In addition to confirming that PAM-proximal mismatches are less tolerated than PAM-distal mismatches, our study further identified a 'core' sequence that is highly sensitive to target-mismatch. This sequence is of 4-nucleotide long, located at +4 to +7 position upstream of PAM, and positioned in a steric restriction region when assembled into Cas9 endonuclease. Our study also found that, single or multiple target mismatches at this region abolished off-target cleavage mediated by active sgRNAs, thus proposing a principle for gene-specific sgRNA design. Characterization of a mismatch sensitive 'core' sequence not only enhances our understanding of how this elegant system functions, but also facilitates our efforts to improve targeting specificity of a sgRNA. [ABSTRACT FROM AUTHOR]

Although small interfering RNAs (siRNAs) have been demonstrated to specifically silence their target genes in disease models and clinical trials, in vivo siRNA delivery is still the technical bottleneck that limits their use in therapeutic applications. In this study, a bifunctional peptide named RGD10-10R was designed and tested for its ability to deliver siRNA in vitro and in vivo. Because of their electrostatic interactions with polyarginine (10R), negatively charged siRNAs were readily complexed with RGD10-10R peptides, forming spherical RGD10-10R/siRNA nanoparticles. In addition to enhancing their serum stability by preventing RNase from attacking siRNA through steric hindrance, peptide binding facilitated siRNA transfection into MDA-MB-231 cells, as demonstrated by FACS and confocal microscopy assays and by the repressed expression of target genes. When RGD10 peptide, a receptor competitor of RGD10-10R, was added to the transfection system, the cellular internalization of RGD10-10R/siRNA was significantly compromised, suggesting a mechanism of ligand/receptor interaction. Tissue distribution assays indicated that the peptide/siRNA complex preferentially accumulated in the liver and in several exocrine/endocrine glands. Furthermore, tumor-targeted delivery of siRNA was also demonstrated by in vivo imaging and cryosection assays. In summary, RGD10-10R might constitute a novel siRNA delivery tool that could potentially be applied in tumor treatment. [ABSTRACT FROM AUTHOR]