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Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness. The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity. Among them, thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection. This smart biomaterial could transform to semisolid phase when the temperature increased. Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe, efficient, and sustained inner ear drug administration. This article introduces the key techniques and the latest progress in this field.

Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.

With the spread of the epidemic worldwide, an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019 (COVID‐19): olfactory or taste disorders. Therefore, clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID‐19 patients is of great significance and urgency. A retrospective study was conducted, which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients, through face‐to‐face interviews and telephone follow‐up. Following the completion of questionnaires, the patients participating in the study, were categorized according to the degree of olfactory and taste disorders experienced, and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded. Among the 229 patients, 31 (13.54%) had olfactory dysfunction, and 44 (19.21%) had gustatory dysfunction. For the patients with olfactory dysfunction, 6 (19.35%) developed severe disease and became critically ill. Olfactory dysfunction appeared before the other symptoms in 21.43% of cases. The proportion of females with olfactory and gustatory dysfunction was higher than that of males (P< 0.001). The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad; the prognosis of patients with olfactory dysfunction is relatively favorable; olfactory and gustatory dysfunction can be used as a sign for early screening; females are more prone to olfactory and gustatory dysfunction. It clarify the incidence and clinical characteristics of olfactory and gustatory dysfunction in Chinese COVID‐19 patients.This investigation compensates for the previous lack of data on olfactory and gustatory dysfunction in Chinese COVID‐19 patients.It provides important clues and evidence for the current screening of patients, especially targeting asymptomatic carriers and worldwide epidemic prevention and control. It clarify the incidence and clinical characteristics of olfactory and gustatory dysfunction in Chinese COVID‐19 patients. This investigation compensates for the previous lack of data on olfactory and gustatory dysfunction in Chinese COVID‐19 patients. It provides important clues and evidence for the current screening of patients, especially targeting asymptomatic carriers and worldwide epidemic prevention and control.

Colorectal cancer liver metastasis (CRLM) is the leading cause of colorectal cancer-related deaths and remains a clinical challenge. Enhancement of glucose uptake is involved in CRLM; however, whether long noncoding RNAs (lncRNAs) participate in these molecular events remains largely unclear. Here, we report an lncRNA, GAL (glucose transporter 1 (GLUT1) associated lncRNA), that was upregulated in CRLM tissues compared with primary colorectal cancer (CRC) tissues or matched normal tissues and was associated with the overall survival rates of CRLM patients. Functionally, GAL served as an oncogene because it promoted CRC cell migration and invasion in vitro and enhanced the ability of CRC cells to metastasize from the intestine to the liver in vivo. Mechanistically, GAL interacted with the GLUT1 protein to increase GLUT1 SUMOylation, inhibiting the effect of the ubiquitin-proteasome system on the GLUT1 protein. GLUT1-knockout (−/+) repressed the GAL-mediated increase in CRC cell uptake of glucose, migrate, and invade in vitro, as well as metastasis from the intestine to the liver in vivo, and enforced expression of GLUT1 rescued GAL knockout-induced biological functions in CRC cells. Taken together, our findings demonstrated that GAL promotes CRLM by stabilizing GLUT1, suggesting that the GAL-GLUT1 complex may act as a potential therapeutic target for CRLM.

Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathological activities in the brain. It happens in a substantial portion of the general population and brings significant burden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affects patients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatment of subjective tinnitus remains challenging. In recent decades, a growing number of studies have shown that subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory central systems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to provide further understanding of its pathogenesis.

Endoscopic submucosal dissection (ESD) is a common procedure to treat early and precancerous gastrointestinal lesions. Via submucosal injection, a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision. Saline is a most common submucosal injection liquid, but the formed liquid pad lasts only a short time, and thus repeated injections increase the potential risk of adverse events. Hydrogels with high osmotic pressure and high viscosity are used as an alternate; however, with some drawbacks such as tissue damage, excessive injection resistance, and high cost. Here, we reported a nature derived hydrogel of gelatin-oxidized alginate (G-OALG). Based on the rheological analysis and compare to commercial endoscopic mucosal resection (EMR) solution (0.25% hyaluronic acid, HA), a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability, higher viscosity and more stable structures. The G-OALG gel also showed lower propulsion resistance than 0.25% HA in the injection force assessment under standard endoscopic instruments, which eased the surgical operation. In addition, the G-OALG hydrogel showed good in vivodegradability biocompatibility. By comparing the results acquired via ESD to normal saline, the G-OALG shows great histocompatibility and excellent endoscopic injectability, and enables create a longer-lasting submucosal cushion. All the features have been confirmed in the living both pig and rat models. The G-OALG could be a promising submucosal injection agent for esophageal ESD.

Introduction: Helicobacter pylorieradication therapy may lead to the perturbation of gut microbiota. We aim to investigate the impact of probiotics on eradication rate and gut microbiota during eradication therapy. Methods: A total of 162 patients receiving bismuth quadruple therapy were enrolled and randomly assigned to groups given probiotics (n= 83) or placebo (n= 79) for 4 weeks. Fecal samples were collected before treatment and 2, 4, 6, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing. Results: The eradication rates in the placebo and probiotics group were 82.43% and 87.01%, respectively (P> 0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both groups, which was restored at week 8. There were no significant differences in diversity between the two groups. H. pylorieradication therapy resulted in enrichment of some detrimental bacteria taxa such as Shigella, Klebsiella, and Streptococcus, while probiotics supplementation could rapidly restore these taxa levels after eradication and increase the taxa of Bacillusand Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Increased relative abundances of Roseburiaand Dialisterwere associated with the positive eradication outcome. Conclusions: Probiotics supplementation might help to construct a beneficial profile of gut microbiota after eradication therapy. Specific bacteria taxa are associated with H. pylorieradication outcome. These findings may be of value in rational use of probiotics during H. pylorieradication. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900022116.

The ultraviolet (UV)/chlorine process has attracted increasing attention for micropollutant abatement. However, the limited hydroxyl radical (HO•) generation and the formation of undesired disinfection byproducts (DBPs) are the two major issues in this process. This study investigated the roles of activated carbon (AC) in the UV/chlorine/AC-TiO2process for micropollutant abatement and DBP control. The degradation rate constant of metronidazole by UV/chlorine/AC-TiO2was 3.44, 2.45, and 1.58 times higher than those by UV/AC-TiO2, UV/chlorine, and UV/chlorine/TiO2, respectively. AC acted as an electron conductor and dissolved oxygen (DO) adsorbent, resulting in the steady-state concentration of HO•that was ∼2.5 times that of UV/chlorine. Compared with UV/chlorine, the formation of total organic chlorine (TOCl) and known DBPs in UV/chlorine/AC-TiO2was reduced by 62.3 and 75.7%, respectively. DBP could be controlled via adsorption on AC, and the increased HO•and decreased chlorine radical (Cl•) and chlorine exposure reduced DBP formation. UV/chlorine/AC-TiO2efficiently abated 16 structurally different micropollutants under environmentally relevant conditions owing to the enhanced generation of HO•. This study provides a new strategy for designing catalysts with photocatalytic and adsorption properties for UV/chlorine to promote micropollutant abatement and DBP control.

SOX10is a causative gene of Waardenburg syndrome (WS) that is a rare genetic disorder characterized by hearing loss and pigment disturbance. More than 100 mutations of SOX10have been found in patients with Type 2 WS (WS2), Type 4 WS (WS4), and more complex syndromes. However, no mutation hotspot has been detected in SOX10,and most cases are sporadic, making it difficult to establish a correlation between the high phenotypic and genetic variability. In this study, a duplication of the 321th cytosine (c.321dupC) was introduced into SOX10in pigs, which induced premature termination of the translation of SOX10 (p.K108QfsX45). The premature stop codon in Exon 3 triggered the degradation of mutant mRNA through nonsense-mediated mRNA decay. However, SOX10c.321dupCinduced a highly similar phenotype of WS2 with heterogeneous inner ear malformation compared with its adjacent missense mutation SOX10c.325A>T. In addition, a site-saturation mutation analysis of the SOX10 N-terminal nuclear localization signal (n-NLS), where these two mutations located, revealed the correlation between SOX10 haploinsufficiency and WS by an in vitroreporter assay. The analysis combining the in vitroassay with clinical cases may provide a clue to clinical diagnoses.

The aim of this study was to improve muscle flaps and to evaluate surgical outcomes with the use of a novel specialized retractor, which is a surgical instrument used to locate and shape a bony seat for minimally invasive cochlear implantation.

Although VPAC1 and its ligand vasoactive intestinal peptide (VIP) are important in gastrointestinal physiology, their involvements in progression of gastrointestinal tumor have not been explored. Here, we found that higher expression of VIP/VPAC1 was observed in gastric cancer compared to the adjacent normal tissues. The increased expression of VIP/VPAC1 in gastric cancer correlated positively with invasion, tumor stage, lymph node, distant metastases, and poor survival. Moreover, high expression of VIP and VPAC1, advanced tumor stage and distant metastasis were independent prognostic factors. VPAC1 activation by VIP markedly induced TRPV4-mediated Ca2+entry, and eventually promoted gastric cancer progression in a Ca2+signaling-dependent manner. Inhibition of VPAC1 and its signaling pathway could block the progressive responses. VPAC1/TRPV4/Ca2+signaling in turn enhanced the expression and secretion of VIP in gastric cancer cells, enforcing a positive feedback regulation mechanism. Taken together, our study demonstrate that VPAC1 is significantly overexpressed in gastric cancer and VPAC1/TRPV4/Ca2+signaling axis could enforce a positive feedback regulation in gastric cancer progression. VIP/VPAC1 may serve as potential prognostic markers and therapeutic targets for gastric cancer.

To understand the crucial role of the klothogene in hearing development in mouse models.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a temporizing maneuver used to decrease hemorrhage, and thus perfusion, below the level of aortic occlusion (AO). We sought to investigate lower extremity ischemia in patients who received REBOA. Between February 2013 and September 2016 patients at a tertiary center that received REBOA and survived more than six hours were enrolled. Thirty-one patients were identified, the mean ISS was 40 ± 14 and inhospital mortality was 39 per cent. Twenty received REBOA in zone 1 (distal thoracic aorta). Three (15%) developed lower extremity compartment syndrome (LECS) after zone 1 REBOA. Injury of iliofemoral arteries and veins was each associated with calf fasciotomies (both P = 0.005). A longer duration of AO at zone 1 was associated with calf and thigh fasciotomy (P = 0.046 and P = 0.048, respectively). Iliofemoral arterial injury was associated with thigh fasciotomy (P = 0.04). Eleven patients received REBOA in zone 3 (distal abdominal aorta). Five (45%) patients underwent fasciotomy; four (36%) due to LECS. Femoral arterial injury was associated with calf fasciotomies (P = 0.02). There was no association with sheath size or laterality and need for fas-ciotomy. Neither groin access for REBOA or AO solely caused limb loss or LECS. The contribution to distal ischemia by REBOA remains unclear in patients with lower extremity injury.

IMPORTANCE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a percutaneous transfemoral balloon technique used in select centers for resuscitation and temporary hemostasis, often instead of emergency department thoracotomy. The ability to perform aortic occlusion (AO) with an intravascular device allows focused occlusion at the most distal level to perfuse proximal regions while slowing hemorrhage to injured areas. OBJECTIVE: To describe what is to date the largest single-institution experience with REBOA in the United States. DESIGN, SETTING, AND PARTICIPANTS: Use of REBOA at an urban tertiary care facility for severe traumatic hemorrhage, traumatic arrest (AR), or nontraumatic hemorrhage (NTH) was investigated from February 1, 2013, to January 31, 2017, among 90 patients who were not responsive or were transiently responsive to resuscitation measures, or were in arrest, from presumed hemorrhage below the diaphragm. Possible causes were trauma or nontrauma-related hemorrhage. Patients with ruptured aortic aneurysms were excluded. MAIN OUTCOMES AND MEASURES: In-hospital mortality. RESULTS: Of the 90 patients in the study (15 women and 75 men; mean [SD] age, 41.5 [17.4] years), 29 underwent REBOA for severe traumatic hemorrhage, 50 for AR, and 11 for NTH. For the patients with severe traumatic hemorrhage and AR, the median age was 36.2 years (interquartile range, 25.3-55.5 years), mean (SD) admission Glasgow Coma Scale score was 6 (5), and median Injury Severity Score was 39 (interquartile range, 10-75). The distal thoracic aorta was occluded in 73 patients (81%), and in all patients with AR. A total of 17 patients (19%) had distal abdominal AO. Mean (SD) systolic blood pressure improved in patients with severe traumatic hemorrhage, from 68 (28) mm Hg prior to AO, to 131 (12) mm Hg after AO (P &lt; .001). Percutaneous access was used in 30 patients (33%), including 13 patients with AR (26%), and groin cutdown in 60 patients (67%), including 37 patients with AR (74%). Overall 30-day mortality was 62% (n = 56): 11 (39%) in patients with severe traumatic hemorrhage and 45 (90%) in patients with AR. Of the patients with AR, 29 (58%) had return of spontaneous circulation and 11 of those patients (38%) survived to the operating room. All patients who survived AR gained full neurologic recovery. No aortoiliac injury or limb loss occurred from REBOA use. Eleven patients underwent REBOA for NTH; 7 (64%) were in arrest. Overall in-hospital mortality for patients with NTH was 36% (n = 4). No procedural complications occurred in this group. CONCLUSIONS AND RELEVANCE: REBOA is a minimally invasive alternative to emergency department thoracotomy with aortic cross-clamp to temporize noncompressible torso hemorrhage and obtain proximal control in both traumatic and nontraumatic causes of hemorrhage. REBOA can also be used for more targeted AO in the distal aorta for pelvic, junctional, or extremity hemorrhage.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9–guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bthallele differs from the wild-type allele at only a single base pair. Injection of Cas9–guide RNA–lipid complexes targeting the Tmc1Bthallele into the cochlea of neonatal Tmc1Bth/+mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+mice. These findings suggest that protein–RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Although the endoscopic treatment of gastric stromal tumors is a recently accepted therapy, the long-term outcomes of this approach remain unknown. The aims of this study were to assess the long-term effectiveness and safety of endoscopic resection for gastric GISTs. A total of 60 consecutive patients undergoing endoscopic resection of gastric GISTs were enrolled in a retrospective single-center study. Clinical data, perioperative complications, histopathologic characteristics of the tumors, and long-term outcomes were recorded. Sixty patients successfully underwent complete resection of lesions, including 25 cases of endoscopic submucosal dissection (ESD) and 35 cases of endoscopic full-thickness resection (EFTR), with an average tumor size of 1.76 ± 1.55 cm (range 0.5–7.6 cm). The average operation time was 43.97 ± 26.95 min (range 11.7–138.9 min). Two cases were observed with an intraoperative hemorrhage of 200 mL, which were successfully managed by hemostatic forceps. Perforations of 2–11 mm of ESD occurred in four cases (4/25) and were well closed with endoclips, with no conversions to surgical operation. Mucosal laceration of esophagus occurred in 1 case, when a large tumor was removed. The average length of hospitalization was 6.50 ± 3.06 days (range 3–21 days). Out of a total of 60 patients, 44 (73.3%) were at very low risk, 10 (16.7%) were at low risk, 5 (8.3%) were at intermediate risk, and 1 (1.7%) was at high risk. All patients were followed-up for 36.15 ± 12.92 months (range 14–73 months). Primary tumor recurrence occurred in 1 patient who underwent a second operation after 32 months, and no other cases were observed to have either tumor recurrence or metastasis. For long-term outcomes, endoscopic resection of ESD or EFTR is a safe and effective approach for removing gastric stromal tumors (<5 cm), and it can be a resection technique for them with no metastasis.

Tinnitus is the abnormal perception of sound in the absence of external sound stimuli. However, the precise mechanisms underlying tinnitus especially on the gene susceptibility remain unclear. Recently, several studies have suggested that the inferior colliculus (IC) may be involved in noise-induced tinnitus.

Sorting single cells from a population was of critical importance in areas such as cell line development and cell therapy. Image-based sorting is becoming a promising technique for the nonlabeling isolation of cells due to the capability of providing the details of cell morphology. This study reported the focusing of cells using microwell arrays and the following automatic size sorting based on the real-time recognition of cells. The simulation first demonstrated the converged streamlines to the symmetrical plane contributed to the focusing effect. Then, the influence of connecting microchannel, flowing length, particle size, and the sample flow rate on the focusing effect was experimentally analyzed. Both microspheres and cells could be aligned in a straight line at the Reynolds number (Re) of 0.027–0.187 and 0.027–0.08, respectively. The connecting channel was proved to drastically improve the focusing performance. Afterward, a tapered microwell array was utilized to focus sphere/cell spreading in a wide channel to a straight line. Finally, a custom algorithm was employed to identify and sort the size of microspheres/K562 cells with a throughput of 1 event/s and an accuracy of 97.8/97.1%. The proposed technique aligned cells to a straight line at low Reynolds numbers and greatly facilitated the image-activated sorting without the need for a high-speed camera or flow control components with high frequency. Therefore, it is of enormous application potential in the field of nonlabeled separation of single cells.

Increasing evidence indicates that gut microbiota may play a key role in vaccination immunity. Here, we investigate whether the human gut microbiota and metabolic function correlate with the BBIBP-CorV vaccine response. A total of 207 participants who received the BBIBP-CorV vaccine are enrolled. The gut microbiome and metabolic functions are investigated using metagenomic sequencing and metabolomic assays. We find that BBIBP-CorV vaccination is accompanied by altered microbiome composition and functional pathways, and the gut microbiome and its functional profiles correlate with the vaccine response. The levels of short-chain fatty acids (SCFAs) are much higher in the high antibody response group compared to the low response group, and several SCFAs display a positive correlation with the antibody response. Our study highlights that the gut microbiome and its function is associated with the BBIBP-CorV vaccine response, providing evidence for further exploration of microbiome modulation to improve COVID-19 vaccine efficacy.

Bioadhesive performance can be compromised due to bleeding. Bleeding increases mortality. Adhesives with hemostatic function are of great significance. A sustainable and robust hemostatic bioadhesive from okra is reported. The adhesive strength reaches around three and six‐fold higher than commercial fibrin on pigskin and glass, respectively. The okra gel presents high‐pressure resistance and great underwater adhesive strength. In human blood experiments, the okra gel can activate platelets, enhance the adhesion of activated platelets, and release coagulation factors XI and XII. By forming a fast gel layer and closely adhering to the wound, it can quickly stop bleeding in the liver and heart of rabbits and dogs. Meanwhile, okra gel can cause platelet activation at the wound site and further strengthen its hemostatic performance. It is biocompatible, biodegradable, and can promote wound healing and shows potential as a sustainable bioadhesive, especially in the scenario of significant hemorrhage. The work reports a robust hemostatic bioadhesive gel from okra. Okra gel is biocompatible and biodegradable. It promotes wound healing. The gel can activate platelets and release the coagulation factors XI and XII, which leads to a strong hemostatic efficiency. The okra gel shows efficay in treating the bleeding trauma model of the liver and the heart of rabbits and beagle dogs.

Bioadhesives In article 2200939, Malcolm Xing, Shiming Yang, and co‐workers report a robust hemostatic bioadhesive gel from okra. Okra gel is biocompatible and biodegradable. It promotes wound healing. The gel can activate platelets and release the coagulation factors XI and XII, which leads to a strong hemostatic efficiency. The okra gel shows efficay in treating the bleeding trauma model of the liver and the heart of rabbits and beagle dogs.

Supplemental digital content is available in the text.

To investigate the membrane localization function of the CX26 protein when its 86th amino acid is Thr, Ser or Arg, and its relations to deafness.

To report detection of vestibular-evoked myogenic potentials (VEMPs) in the miniature pig.

Supplemental Digital Content is available in the text.Published ahead of print August 21, 2015

Cell–cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions.

The Atmosphere‐Space Interactions Monitor was designed to monitor Terrestrial Gamma‐ray Flashes (TGFs) and Transient Luminous Events (TLEs) from space, enabling the study of how these phenomena are related. In this paper, we present observations of 17 TGFs with accompanying Elves. TGFs are short and highly energetic bursts of gamma photons associated with lightning discharges, whereas Elves are TLEs that are observed as concentric rings of ultraviolet (UV) and visible light at ionospheric altitudes, produced by the excitation of N2molecules when an electromagnetic pulse hits the base of the ionosphere. Elves were identified when optical detections in the UV band could be clearly distinguished from other optical signals from lightning strokes. The TGFs they accompanied had short durations and were associated with particularly high peak current lightning. Lightning sferics associated with these events were detected by the global lightning network GLD360 and the World Wide Lightning Location Network, and they were, with the exception of one event, observed over ocean or coastal regions. It is likely that these events were associated with Energetic In‐cloud Pulses. We show that short duration TGFs tend to be associated with higher peak currents than long duration TGFs. We present a sample of 17 Terrestrial Gamma‐ray Flashes (TGFs) with accompanying Elves detected by Atmosphere‐Space Interactions MonitorTGFs with Elves are short and associated with very high peak current lightningThe peak currents for these events are higher than for both lightning and TGFs in general We present a sample of 17 Terrestrial Gamma‐ray Flashes (TGFs) with accompanying Elves detected by Atmosphere‐Space Interactions Monitor TGFs with Elves are short and associated with very high peak current lightning The peak currents for these events are higher than for both lightning and TGFs in general

Secondary insults such as hypotension, hypoxia, cerebral hypoperfusion, and intracranial hypertension are associated with poor outcome following severe traumatic brain injury (TBI). Preventing and minimizing the effect of secondary insults are essential in the management of severe TBI. At present, clinicians have no way to predict the development of these events, limiting their ability to plan appropriate timing of interventions. We hypothesized that processing continuous vital signs (VS) data using machine learning methods could predict the development of future intracranial hypertension.

To identify transcript variants and expression patterns of porcine Mitf.

The development of auditory synapses is a key process for the maturation of hearing function. However, it is still on debate regarding whether the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.

The impact of miRNA differential expression on the auditory epithelium stem cell development in postnatal rats is not clear. The present study was designed to analyze miRNA expression in the organ of Corti of neonatal and adult rats. The cochleae of newborn (P0) and adult (P30) Sprague-Dawley rats were dissected in cold PBS to collect the sensory epithelia. Small RNAs were extracted using the mirVana RNA Isolation kit. Then, miRNA expression profiling was performed with RNAs from three newborns and three adult rats utilizing the TaqMan Array Rodent MicroRNA Panel. Eighteen miRNAs were found be differentially expressed, 16 were unregulated in mature cochleae with the fold changes ranging from 17 to 600 folds. The expression levels of two miRNAs were reduced in the mature rat cochleae. GO analysis and signaling pathway analysis revealed the potential involvement of the miRNAs in the regulation of Wnt and TGF-ß signaling pathways in hair cell development. Our results provided novel insights into the functional significance of miRNAs in the basilar membrane cells development, and revealed the potential importance of miRNAs in the hair cell by regulation of Wnt and TGF-ß signaling.

Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals. However, the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements. In this article, we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models. Ten one-week old normal mini pigs were used in the study. The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements. The condition of the animals during the first post–experiment 24 h was observed. One animal died during surgery. The pre-auricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid artery. So, the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.

Massive clinical digital data routinely collected by high throughput biomedical devices provide opportunities and challenges for optimal use. This article discusses how such data are used in learning prediction models at level 1 trauma centres to support decision making in trauma patients.

Background: The present study was designed to evaluate the efficacy and safety of a combination of helical tomotherapy (HT) or intensity-modulated radiotherapy (IMRT) and EGFR (epidermal growth factor receptor) inhibitor (Cetuximab or Nimotuzumab) with or without chemotherapy in patients with locally advanced hypopharyngeal carcinoma. Patients and Methods: The retrospective study included forty-six patients (12 stage III and 34 stage IV) with locally advanced hypopharyngeal cancer. Among them, 20 were treated with induction chemotherapy with docetaxel and cisplatin (TP) followed by concurrent chemoradiotherapy with cisplatin and EGFR inhibitor, 13 received concurrent chemoradiotherapy with cisplatin and EGFR inhibitor, and 13 were treated with concurrent radiotherapy plus EGFR inhibitor. HT and IMRT were performed in 33 and 13 patients, respectively. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 3.0 criteria. Results: The median follow-up time was 39.4 months (range 3-69 months). All patients completed the planned RT without any treatment breaks. The 3-year local control survival, disease-free survival, overall survival, and laryngeal preservation survival rates were 66.8%, 59.0%, 68.9%, and 86.7%, respectively. The most common grade 3 or higher side effect was oropharyngeal mucositis. One patient required dilatation of a pharyngeal stricture 18 months after treatment. No patient required percutaneous gastrostomy and tracheostomy tube. Conclusion: The treatment with EGFR inhibitor in combination with non-surgical combined modality in patients with hypopharyngeal carcinoma was well tolerated and resulted in encouraging laryngeal preservation survival rate. HT or IMRT, EGFR inhibitor, and effective management of severe oropharyngeal mucositis contributed to the positive outcomes.

The accepted treatment of increased intracranial pressure (ICP) in patients experiencing severe traumatic brain injury is multimodal and algorithmic, obscuring individual effects of treatment. Using continuous vital signs monitoring, we sought to measure treatment effect and ascertain the accuracy of manual data recording.

Cyclooxygenase-2 (COX-2) inhibitor, celecoxib, causes growth inhibition of human gastric carcinoma cells, but it remains unclear whether celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells. The adenine nucleotide translocator (ANT) is a mitochondrial bi-functional protein. We speculate that ANT-dependent pathways might contribute to H. pylori-induced invasion and metastasis of gastric cancer cells. Therefore, in the present study, we evaluate the effect of celecoxib on H. pylori-induced gastric cancer cell motility and invasion. We also explore the role of ANTs in H. pylori-induced gastric cancer cell motility and invasion of gastric cancer cell line AGS. Our results demonstrate that celecoxib induces anoikis-like apoptosis and suppresses the proliferation and invasion of gastric cancer cells induced by H. pylori in culture. RT-PCR and Western blot analysis indicates that celecoxib upregulates the expression of ANT1 and ANT3; however, celecoxib did not increase the expression of ANT2. Our results suggest that celecoxib could be an effective means for suppressing proliferation and invasion of gastric cancer cells induced by H. pylori through an adenine nucleotide translocator-dependent mechanism.

1.StSN2 and StGAPC1 expression level decreased more in sprouting than dormancy both on transcription and protein process. The coexpression of StSN2 and StGAPC1 in bud eyes and apical buds was verified by immunofluorescence of paraffin sections.2.StSN2 interaction with StGAPC1 was confirmed by in vivoand in vitroexperiments. Overexpression of StGAPC1 depressed sprout growth, similar to StSN2 function.3.StSN2 interaction with StGAPC1 increased StGAPC1 activity and decreased its oxidative modification to inhibit sprout growth.The potato tuber is the main nutrient supply and reproductive organ; however, tuber sprouting can reduce its commercial value. Snakin-2 (StSN2) was first reported as an antimicrobial peptide that positively regulates potato disease resistance. Our recent study suggested StSN2overexpression inhibited sprout growth, while the sprouting process was accelerated in StSN2RNAi lines. Cytoplasmic glyceraldehyde-3-phosphate dehydrogenase 1 (StGAPC1) was identified as a candidate protein that interacts with StSN2 in co-immunoprecipitation/mass spectrometry experiments. Here, we report that the expression levels of StSN2and StGAPC1decreased during sprouting compared with dormancy. Coexpression of StSN2 and StGAPC1 in bud eyes and apical buds was verified by immunofluorescence analysis of paraffin sections. In addition, interaction of StSN2 and StGAPC1 was confirmed by yeast two-hybrid, co-immunoprecipitation, and split luciferase complementation assays. Overexpression of StGAPC1depressed sprout growth, which is similar to the function of StSN2, and StSN2- and StGAPC1-overexpressing lines showed decreased glucose, fructose, and galactose contents. The interaction of StSN2 and StGAPC1 enhanced StGAPC1 activity and decreased its oxidative modification to inhibit sprout growth. Our results suggest that StSN2 plays a regulatory role in tuber sprout growth through interaction with StGAPC1.

•Multi-shelled NiCo2S4hollow microspheres are prepared by using carbon spheres as templates.•Multi-shelled NiCo2S4hollow microspheres have multiple shell structures and large specific surface area.•Multi-shelled NiCo2S4hollow microspheres exhibit excellent electrochemical performance.

We asked whether the advanced machine learning applications used in microarray gene profiling could assess critical thresholds in the massive databases generated by continuous electronic physiologic vital signs (VS) monitoring in the neuro-trauma intensive care unit.

The Br/+ mutant mouse displays decreased embryological expression of the homeobox transcription factor Six2, resulting in hertitable renal hypoplasia. The purpose of this study was to characterize the renal physiological consequences of embryonic haploinsuffiency of Six2by analyzing renal morphology and function in the adult Brheterozygous mutant. Adult Br/+ kidneys weighed 50% less than those from wild-type mice and displayed glomerulopathy. Stereological analysis of renal glomeruli showed that Br/+ kidneys had an average of 88% fewer glomeruli than +/+ kidneys, whereas individual glomeruli in Br/+ mice maintained an average volume increase of 180% compared with normal nephrons. Immunostaining revealed increased levels of endothelin-1 (ET-1), endothelin receptors A (ETA) and B (ETB), and Na-K-ATPase were present in the dilated renal tubules of mutant mice. Physiological features of chronic renal failure (CRF) including elevated mean arterial pressure, increased plasma creatinine, and dilute urine excretion were measured in Br/+ mutant mice. Electron microscopy of the Br/+ glomeruli revealed pathological alterations such as hypercellularity, extracellular matrix accumulation, and a thick irregular glomerular basement membrane. These results indicate that adult Br/+ mice suffer from CRF associated with reduced nephron number and renal hypoplasia, as well as glomerulopathy. Defects are associated with embryological deficiencies of Six2, suggesting that proper levels of this protein during nephrogenesis are critical for normal glomerular development and adult renal function.

Based on classical analysis and conclusive comments about various kinds of drying models, a rigorously formulated and comprehensive theoretical model is established to describe heat and mass transfer during constant rate and falling rate periods in convective drying of porous materials. The concept of iterative correction is introduced, and a corresponding numerical method is developed for the moving boundary problem in numerical simulations of drying processes. The calculation results for the drying of bricks show that the model presented is more precise than other models. © 1999 Scripta Technica, Heat Trans Asian Res, 28(5): 337–351, 1999

Based on classical analysis and conclusive comments about various kinds of drying models, a rigorously formulated and comprehensive theoretical model is established to describe heat and mass transfer during constant rate and falling rate periods in convective drying of porous materials. The concept of iterative correction is introduced, and a corresponding numerical method is developed for the moving boundary problem in numerical simulations of drying processes. The calculation results for the drying of bricks show that the model presented is more precise than other models. © 1999 Scripta Technica, Heat Trans Asian Res, 28(5): 337–351, 1999

•A self-sacrificial template approach was developed to prepare Co3O4nanoarray.•Co3O4with different pore size was prepared by changing molality of precursor.•It showed high specific capacity, outstanding rate capability and excellent stability.•The excellent performance is attributed to the hollow nanoarray structure.