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There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery.From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC.The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group.Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

Background The prediction of response to chemotherapy can lead to the optimization of neoadjuvant chemotherapy (NAC). This study aimed to develop a predicting model of therapeutic response to NAC for rectal cancer (RC). Methods Three courses of S-1 and oxaliplatin (SOX) NAC were administered before total mesorectal excision. We collected the dataset for the prechemotherapy arterial phase of enhanced computed tomography (CT) images from 57 patients undergoing rectal surgery after NAC for RC. In all cases, the therapeutic response to NAC had been pathologically confirmed. We established three prediction labels; poor response, marked response, and complete response (CR). We built a predictive model using a residual convolutional neural network (ResNet50) and used 3-fold cross-validation. The prediction accuracy of the model was analyzed. Results Of the 57 patients, pathological CR was observed in 9 (15.8%). A total of 4,607 squares were extracted from the segmented tumor area of each patient. The average accuracy of the ResNet model for predicting pathological CR was 99.9% for the training dataset. In the test dataset, the average accuracy was 94.9%. Likewise, in the prediction of marked and poor responses, the models demonstrated high accuracy (93.6% and 93.3%, respectively) and high AUC (0.966 and 0.976, respectively). Conclusions Our deep learning model, using prechemotherapy CT images of RC, exhibited high predictive performance in projecting therapeutic response to SOX NAC. This study presents a novel insight into the optimization of NAC for RC.

To optimize the use of neoadjuvant chemotherapy (NAC), this study aimed to develop a therapeutic response prediction model with NAC for rectal cancer (RC). Three courses of S-1 and oxaliplatin (SOX) NAC were administered before rectal surgery. We prospectively collected the dataset for the prechemotherapy arterial phase of enhanced computed tomography (CT) images from 57 RC patients undergoing rectal surgery after NAC. The therapeutic response to NAC had been pathologically confirmed. We established three prediction labels: poor response, marked response, and complete response (CR). We built a CT patch-based predictive model using a residual convolutional neural network and used 3-fold cross-validation. Of the 57 patients, pathological CR was observed in 9 (15.8%). A total of 4,607 patches were extracted from the segmented tumor area of each patient. The accuracy of the model for predicting pathological CR was 99.9% for the training dataset. In the validation dataset, the accuracy was 94.9%. Furthermore, the area under the curve (AUC) was 0.949. Likewise, in the prediction of marked and poor response, the models demonstrated high accuracy (93.6% and 93.3%, respectively) and high AUC (0.966 and 0.976, respectively). Our CT-based deep learning model exhibited high predictive performance in projecting therapeutic response to SOX NAC.

Preoperatively accurate evaluation of risk for postoperative recurrence contributes to maximizing the therapeutic success of surgical resection for intrahepatic cholangiocarcinoma (iCCA). This study aimed to investigate the potential of deep learning (DL) algorithms for predicting postoperative early recurrence through the use of preoperative images. We collected the dataset, including preoperative plain computed tomography (CT) images, from 41 patients undergoing curative surgery for iCCA at multiple institutions. We built a CT patch-based predictive model using a residual convolutional neural network and used 5-fold cross-validation. The prediction accuracy of the model was analyzed. We defined early recurrence as recurrence within a year after surgical resection. Of the 41 patients, early recurrence was observed in 20 (48.8%). A total of 71,081 patches were extracted from the entire segmented tumor area of each patient. The average accuracy of the ResNet model for predicting early recurrence was 98.2% for the training dataset. In the validation dataset, the average sensitivity, specificity, and accuracy were 97.8%, 94.0%, and 96.5%, respectively. Furthermore, the area under the receiver operating characteristic curve was 0.994. Our CT-based DL model exhibited high predictive performance in projecting postoperative early recurrence, proposing a novel insight into iCCA management.

In recent years, stenting and stoma creation as a bridge to surgery for obstructive left-sided colon cancer have been attracting attention. Our team has a stent-independent strategy and performs primary resection after stoma construction and preoperative chemotherapy with cT4 patients. In this study, we investigated both its validity and issues. Sixty-five cases of scope-impassable left-sided colon cancer surgeries from November 2015 to September 2020 were included. The short- and long-term results were examined in Stage Ⅱ-Ⅲ and Ⅳ. The median time from admission to surgery was 6 days and 8 days, respectively; postoperative morbidity was 9.5% and 17.4%, respectively; anastomotic leakage was 4.8% and 17.4%, respectively; permanent stoma was 26.2% and 21.7%, respectively; and postoperative death was zero in both groups. In group Ⅱ-Ⅲ, the 3-year overall survival rate was 77.0%, 3-year disease-free survival rate was 72.7%, and in group Ⅳ, the 3-year overall survival rate was 36.0%. Local recurrence was observed in 2(16.7%)of 12 patients with cT3-4N+ rectosigmoid cancer who did not receive neoadjuvant chemotherapy. The stent-independent strategy was safe with low morbidity, and the permanent stoma rate was reasonable.

The patient was a 57-year-old male. He was diagnosed with locally advanced rectal cancer infiltrating the left levator ani muscle. Chemotherapy(S-1 plus L-OHP plus bevacizumab regimen)was started for the purpose of obtaining a negative circumferential radial margin. After the second course, he presented with perforation of the sigmoid colon for which an emergency operation was performed. The perforation was located 5 centimeters above the tumor in the sigmoid colon. We performed partial resection of the sigmoid colon to repair the perforation and create a sigmoid colostomy. CT, after the initial S-1 plus L-OHP plus bevacizumab chemotherapy regimen, revealed tumor shrinkage. Following 2 more courses of chemotherapy( S-1 plus L-OHP regimen), we performed transanal total mesenteric excision(taTME)as curative surgery. R0 resection was achieved. The combined transanal and laparoscopic approach was highly effective for a patient with pan-peritonitis.

OBJECTIVE We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients. METHODS Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT. RESULTS In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015-3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071). CONCLUSIONS This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC.

Presbyopia treatments using various modalities have been developed recently, however, no standard criteria exist for the diagnosis and treatment endpoint. This study assessed the relationship between the near visual acuity (NVA) and the subjective symptoms of phakic presbyopia and determined the numerical NVA threshold to diagnose phakic presbyopia and evaluate the effectiveness of presbyopia treatment. The binocular distance, NVA with habitual correction, and monocular conventional VA were measured. Patients were asked about their awareness of presbyopia and difficulty performing near tasks. This prospective observational study included 70 patients (mean age, 56 years, range, 32–77). Most patients became aware of presbyopia in their late forties, although some had difficulty with vision-related near tasks before becoming aware of presbyopia. Eighty three percent of patients (20/24) experienced difficulty with near vision-related tasks even with excellent NVA at 40 cm with habitual correction of 0.0 logMAR (20/20 in Snellen VA). In conclusion, the current study showed that patients became aware of presbyopia in their late forties, although some had difficulty with near vision-related tasks before becoming aware of presbyopia. Further investigation should include the proposal of appropriate diagnostic criteria for presbyopia and better management for patients with presbyopia.

An 82-year old man was admitted for a left fifth rib fracture with traumatic pneumothorax. Computed tomography showed a sharp rib fragment protruding into the thoracic cavity. Thoracic drainage was not performed before surgery to avoid lung injury by the rib fragment. At surgery, fifth rib fragment protruding into the thoracic cavity was found, but lung injury was not present. The bone fragment was removed, and the patient's postoperative course was uneventful.

The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2 on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2 concentration (p p p 2 significantly increased tear secretion in healthy mice (p p = 0.007). H2 significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2 may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.

The reported growth rate of vestibular schwannoma varied widely in the literature. However, emergence of vestibular schwannoma remains unsolved. We presented three patients who had undergone previous magnetic resonance imaging (MRI) confirming the absence of tumor and were diagnosed with a unilateral vestibular schwannoma with a diameter of 18-30 mm, 6-9 years after the initial MRI. One patient had solid tumor and experienced stereotactic radiosurgery. Following stereotactic radiosurgery, continuous tumor growth led to hydrocephalus and trigeminal dysfunction, resolved by surgical removal. Other two patients had the tumor with cystic component and experienced surgical removal as first treatment. All tumors were pathologically diagnosed as schwannomas without evidence of high potential of proliferation. This is the first report of three patients with de novo vestibular schwannoma, showing tumor emergence and rapid growth in a short period. Considering a de novo aspect, the "wait and scan" policy may not be appropriate for the subset of VS such as de novo VS.

Massive intraoperative blood loss (IBL) negatively influence outcomes after surgery for pancreatic ductal adenocarcinoma (PDAC). However, few data or predictive models are available for the identification of patients with a high risk for massive IBL. This study aimed to build a model for massive IBL prediction using a decision tree algorithm, which is one machine learning method. One hundred and seventy-five patients undergoing curative surgery for resectable PDAC at our facility between January 2007 and October 2020 were allocated to training (n = 128) and testing (n = 47) sets. Using the preoperatively available data of the patients (34 variables), we built a decision tree classification algorithm. Of the 175 patients, massive IBL occurred in 88 patients (50.3%). Binary logistic regression analysis indicated that alanine aminotransferase and distal pancreatectomy were significant predictors of massive IBL occurrence with an overall correct prediction rate of 70.3%. Decision tree analysis automatically selected 14 predictive variables. The best predictor was the surgical procedure. Though massive IBL was not common, the outcome of patients with distal pancreatectomy was secondarily split by glutamyl transpeptidase. Among patients who underwent PD (n = 83), diabetes mellitus (DM) was selected as the variable in the second split. Of the 21 patients with DM, massive IBL occurred in 85.7%. Decision tree sensitivity was 98.5% in the training data set and 100% in the testing data set. Our findings suggested that a decision tree can provide a new potential approach to predict massive IBL in surgery for resectable PDAC.

Leber congenital amaurosis type 9 (LCA9) is an autosomal recessive, early onset retinal neurodegenerative disease caused by mutations in the gene encoding the nuclear NAD + synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1 and its role in NAD + homeostasis, LCA9 patients do not manifest pathologies other than retinal degeneration. To investigate the mechanism of degeneration, we examined retinas of developing and adult mice with conditional or tissue-specific NMNAT1 loss. Widespread NMNAT1 depletion in adult mice resulted in loss of photoreceptors, indicating these cells are exquisitely vulnerable to NMNAT1 loss. NMNAT1 is required within the photoreceptor, as conditional deletion of NMNAT1 in photoreceptors but not retinal pigment epithelial cells is sufficient to cause photoreceptor neurodegeneration and vision loss. Moreover, delivery of NMNAT1 into eyes of adult mice lacking NMNAT1 using a modified AAV8 vector containing a photoreceptor-specific promoter rescued the retinal degeneration phenotype and partially restored vision. Finally, we defined the molecular mechanism driving photoreceptor cell death. Loss of NMNAT1 activates SARM1, an inducible NADase best known as the central executioner of axon degeneration. SARM1 is required for the photoreceptor death and vision loss that occurs following NMNAT1 deletion. This surprising finding demonstrates that the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, and establishes a commonality of mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway that is active in the setting of dysregulated NAD + metabolism and identifies SARM1 as a therapeutic candidate for the treatment of retinal degeneration.

Presbyopia is increasing globally due to aging and the widespread use of visual display terminals. Presbyopia is a decrease in the eye&rsquo, s amplitude of accommodation (AA) due to loss of crystalline lens elasticity. AA differs widely among individuals. We aimed to determine the factors that cause presbyopia, other than advanced age, for early medical intervention. We examined 95 eyes of 95 healthy volunteers (33 men, 62 women) aged 22&ndash, 62 years (mean: 37.22 &plusmn, 9.77 years) with a corrected visual acuity of &ge, 1.0 and without other eye afflictions except ametropia. Subjective refraction, AA, maximum and minimum pupillary diameters during accommodation, axial length of the eye, and crystalline lens thickness were measured. AA was measured using an auto refractometer/keratometer/tonometer/pachymeter. The difference between maximum and minimum pupillary diameters was calculated. On multiple regression analysis, age and difference in pupillary diameter were both significantly and independently associated with AA in participants aged &lt, 44 years, but not in those aged &ge, 45 years. Our results suggest that the difference in pupillary diameter could be an important age-independent factor for evaluating AA in healthy individuals without cataract. Thus, improving the difference in pupillary diameter values could be an early treatment target for presbyopia.

Recently Distributed Acoustic Sensing (DAS) measurement which utilizes an optical fiber itself as a sensor becomes popular. In 1996, a seafloor seismic tsunami observation system using an optical fiber cable was deployed off Sanriku by Earthquake Research Institute, the University of Tokyo. The system has spare (dark) optical fibers without repeaters. We start development of a seafloor seismic observation system by the DAS technology with Sanriku cable observation system as a next generation of marine seismic observation system. In February 2019, we made a pilot observation of a DAS measurement using a dark fiber of Sanriku seafloor observation system. The data were collected continuously for about 46 hours and many earthquakes including micro-earthquakes and a deep earthquake were recorded.

Gallium nitride (GaN)-based P-channel (Pch) and N-channel (Nch) metal-oxide-semiconductor field-effect transistors (MOSFETs) with normally off operations were realised. Both Pch and Nch MOSFETs were monolithically fabricated in a polarisation-junction platform wafer. The platform wafer was constructed with a GaN/aluminium GaN/GaN double heterostructure, which has both two-dimensional hole gas (2DHG) and 2D electron gas (2DEG). The drain currents of Pch and Nch MOSFETs flow through 2DHG and 2DEG, respectively. The threshold gate voltages of the fabricated Pch and Nch MOSFETs were -2.7 and 6.7 V, respectively. It was shown that the threshold voltage and the on-state resistance of the Pch MOSFET can be controlled by adjusting the 2DEG potential. Furthermore, using Pch and Nch MOSFETs, complementary MOS inverter operation was demonstrated.

Summary Photoreceptor death is the endpoint of many blinding diseases. Identifying unifying pathogenic mechanisms in these diseases may offer global approaches for facilitating photoreceptor survival. We found that rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase ( Nampt ), the rate-limiting enzyme in the major NAD + biosynthetic pathway beginning with nicotinamide, caused retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN). Significantly, retinal NAD + deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction. Mechanistically, NAD + deficiency caused metabolic dysfunction and consequent photoreceptor death. We further demonstrate that the NAD + -dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD + deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD + biosynthesis is essential for vision, provide a foundation for future work to further clarify the mechanisms involved, and identify a unifying therapeutic target for diverse blinding diseases.

Bilateral complex vertebral artery aneurysms (BCoVAAns) have no established strategy of management. We retrospectively reviewed five consecutive patients with unruptured BCoVAAns between January 2006 and December 2012. Considering surgical risks of lower cranial nerve (LCN) injuries and eventual growth of an opposite side lesion after unilateral vertebral artery (VA) occlusion, we proposed a strategy of combined open and interventional treatment using revascularization. We applied the following several specific techniques: (1) proximal clipping and occipital artery-posterior inferior cerebellar artery (OA-PICA) and/or superficial temporary artery (STA)-superior cerebellar artery (SCA) bypasses; (2) Distal blood pressure, motor evoked potentials (MEPs), and somatosensory evoked potentials (SEPs) monitoring after parent artery temporary occlusion for safe permanent occlusion of the proximal portions of VA and PICA; (3) V3 to V4 bypass using radial artery (RA) graft with proximal clipping or trapping, two of them combined with OA-PICA bypass; (4) VA fenestration as an opportunity to preserve the flow of the parent artery. Two patients were treated bilaterally and 3 unilaterally, with modified Rankin scale assessed at 39 months postoperatively in average 0 in 2, 1 in 2, and 2 in 1, respectively, and the untreated opposite side lesions without regrowth or bleeding. Two patients with patent V3-RA-V4 bypass complained of dysphagia due to LCN palsies. One of them however suffered a cerebellar infarction due to occlusion of the OA-PICA bypass. When BCoVAAns require surgical treatment, revascularization or preservation of the VA should be considered at the first operation. By doing so, the opposite aneurysm can be effectively occluded by coil embolization, even with VA sacrifice if required.

Sirtuins are NAD+-dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+-dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis. Our results suggest that SIRT1, SIRT2, SIRT4, and SIRT6 are dispensable for retinal survival at baseline, as individual deletion of each of these sirtuins does not cause retinal degeneration by fundus biomicroscopy or retinal dysfunction by ERG. These findings have significant implications and inform future studies investigating the mechanisms underlying the central role of NAD+ biosyn-thesis in retinal survival and function.

SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders., Author Summary Sirtuins are nicotinamide adenine dinucleotide-dependent protein deacetylases. Among seven sirtuins, SIRT3 is a key regulator of mitochondrial function. However, functions of SIRT3 in the retina are largely unknown. In this study, we investigated the role of retinal SIRT3 in a mouse model of light-induced retinal degeneration, found that SIRT3 has neuroprotective role in the retina. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress, and decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These results suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.

Polarization junction platforms have high-density 2D hole gas (2DHG) and 2D electron gas (2DEG) respectively induced by negative and positive polarization charges in undoped GaN/AlGaN/GaN double heterostructures. Sheet resistance measurements in a wide temperature range (6–460 K) revealed that 2DHG and 2DEG resistances were monotonically enhanced with the temperature reduction. On the platform, monolithic operations of GaN-based devices including high-voltage n-channel (N-ch) transistors, N-ch Schottky diodes, low-voltage N-ch transistors and p-channel transistors has been demonstrated.

The development of choroidal neovascularization (CNV) is a critical step in the pathogenesis of age-related macular degeneration (AMD), a vision-threatening disease. In this study, we used a mouse model of AMD to study the protective effects of resveratrol (RSV) supplementation against CNV as well as the underlying molecular mechanisms. Mice were orally pretreated with RSV daily for 5days. On the fifth day, the mice underwent laser photocoagulation to induce CNV. One week after laser treatment, CNV volume was significantly lower in the RSV-treated mice compared with vehicle-treated animals. In addition, RSV treatment significantly inhibited macrophage infiltration into the retinal pigment epithelium (RPE)-choroid and suppressed the expression of inflammatory and angiogenic molecules, including vascular endothelial growth factor, monocyte chemotactic protein-1 and intercellular adhesion molecule-1. Importantly, RSV prevented the CNV-induced decrease in activated AMP-activated protein kinase and increase in activated nuclear factor-κB in the RPE-choroid complex. The regulatory effects of RSV on these molecules were confirmed in RPE, microvascular endothelial and macrophage cell lines. Inhibition of macrophage infiltration by RSV was confirmed by in vitro scratch and migration assays. RSV suppressed CNV development, reducing the levels of multiple cytokines secreted from several cell types and inhibiting macrophage migration. The direct effects of RSV on each cell type were confirmed in vitro. Although further studies are needed, RSV could potentially be applied in the clinic to prevent CNV development in AMD.

This paper gives an overview of GaN-based polarization-junction (PJ) technologies. PJ platform wafers have both high-density 2D hole gas (2DHG) and 2D electron gas (2DEG) respectively induced by negative and positive polarization charges in undoped GaN/AlGaN/GaN double heterostructures. On the platform, monolithic operations of GaN-based n-channel transistors and p-channel transistors have been demonstrated. Because of temperature independent properties of the 2DHG and 2DEG, the GaN devices can operate in wide temperature range. In addition, high voltage transistors and diode are also available on the platform by using polarization-superjunction concept.

Macrophage dysfunction plays a pivotal role during neovascular proliferation in diseases of ageing including cancers, atherosclerosis and blinding eye disease. In the eye, choroidal neovascularization (CNV) causes blindness in patients with age-related macular degeneration (AMD). Here we report that increased IL10, not IL4 or IL13, in senescent eyes activates STAT3 signalling that induces the alternative activation of macrophages and vascular proliferation. Targeted inhibition of both IL10 receptor-mediated signalling and STAT3 activation in macrophages reverses the ageing phenotype. In addition, adoptive transfer of STAT3-deficient macrophages into eyes of old mice significantly reduces the amount of CNV. Systemic and CD163+ eye macrophages obtained from AMD patients also demonstrate STAT3 activation. Our studies demonstrate that impaired SOCS3 feedback leads to permissive IL10/STAT3 signalling that promotes alternative macrophage activation and pathological neovascularization. These findings have significant implications for our understanding of the pathobiology of age-associated diseases and may guide targeted immunotherapy., Pathological neovascularization causes blinding eye disease. Here the authors show that IL10 activates STAT3 signalling in the macrophages in the ageing eye, promoting their polarization towards a pro-angiogenic phenotype; interfering with this pathway reverses the pathology in a mouse model.

Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation.