Stray light analysis and suppression method of a pancake virtual reality head-mounted display.

Pancake virtual reality head-mounted displays (VR-HMDs) have attracted the attention of researchers in both academia and industry because of the compact size and light weight. However, owing to the use of optical path folding, there exist various stray lights in the optical system, which seriously degrades user experience. In this study, we analyze the causes and effects of multiple types of stray light systematically and design a VR-HMD with low stray light, large exit pupil diameter (EPD), compact form and light weight. Subsequently, several effective stray light suppression solutions are proposed and implemented. Finally, a prototype of a compact pancake VR-HMD system is successfully demonstrated. The prototype has stray light of less than 2.3%, a diagonal field of view (FOV) of 96° and an EPD of 10 mm at an 11 mm eye relief (ERF).

Design, stray light analysis, and fabrication of a compact head-mounted display using freeform prisms.

It has been a challenge to design an optical see-through head-mounted display that is compact, lightweight, and stray-light-suppressed by using freeform optics. A new type of design based on freeform prisms is presented. The system consists of three optical elements and a micro-display. Two prisms serve as near-eye viewing optics that magnify the image displayed by the micro-display, and the other freeform lens is an auxiliary element attached to the main wedge-shaped prism to provide an undistorted see-through view of a real-world scene. The overall thickness of the optical system does not exceed 9.5 mm, and the weight is less than 9.8 g per eye. The final system is based on a 0.49-inch micro-display and features a diagonal field of view of 38°, an F/number of 1.8, with a 10 mm × 7 mm exit pupil diameter, and a 19 mm eye relief. The causes of stray light in the optical-mechanical system are investigated, and effective solutions or theoretical suppression of stray light are given. The freeform optical elements are successfully fabricated, and the system performance is carefully investigated. The results show that the performance of the optical see-through head-mounted display is adequate for practical applications.

Bronze and Iron Age population movements underlie Xinjiang population history.

The Xinjiang region in northwest China is a historically important geographical passage between East and West Eurasia. By sequencing 201 ancient genomes from 39 archaeological sites, we clarify the complex demographic history of this region. Bronze Age Xinjiang populations are characterized by four major ancestries related to Early Bronze Age cultures from the central and eastern Steppe, Central Asian, and Tarim Basin regions. Admixtures between Middle and Late Bronze Age Steppe cultures continued during the Late Bronze and Iron Ages, along with an inflow of East and Central Asian ancestry. Historical era populations show similar admixed and diverse ancestries as those of present-day Xinjiang populations. These results document the influence that East and West Eurasian populations have had over time in the different regions of Xinjiang.

Optical design and pupil swim analysis of a compact, large EPD and immersive VR head mounted display.

Virtual reality head-mounted displays (VR-HMDs) are crucial to Metaverse which appears to be one of the most popular terms to have been adopted over the internet recently. It provides basic infrastructure and entrance to cater for the next evolution of social interaction, and it has already been widely used in many fields. The VR-HMDs with traditional aspherical or Fresnel optics are not suitable for long-term usage because of the image quality, system size, and weight. In this study, we designed and developed a large exit pupil diameter (EPD), compact, and lightweight VR-HMD with catadioptric optics. The mathematical formula for designing the catadioptric VR optics is derived. The reason why this kind of immersive VR optics could achieve a compact size and large EPD simultaneously is answered. Various catadioptric forms are systematically proposed and compared. The design can achieve a diagonal field of view (FOV) of 96° at -1 diopter, with an EPD of 10 mm at 11 mm eye relief (ERF). The overall length (OAL) of the system was less than 20 mm. A prototype of a compact catadioptric VR-HMD system was successfully developed.

Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.

Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

Current Smoking is a Risk Factor for the Irregular Surface and Calcification of Carotid Plaque in Men.

OBJECTIVE: To explore whether current smoking could influence plaque characteristics and determine its correlation to the irregular surface and calcification of carotid plaque. METHODS: Three hundred and seventeen patients with severe carotid atherosclerosis stenosis (SCAS) detected by color duplex flow imaging (CDFI) and confirmed by CT angiography (CTA) were recruited. The results of laboratory parameters were collected by using electronic database of the hospital. Computerized tomography (CT) scanning and high-resolution ultrasonography were performed for assessment of plaque morphology, respectively. RESULTS: All enrolled smokers and non-smokers had no significant difference among all characteristics not related to smoking. CT scanning could efficiently identify the difference among enrolled smokers and non-smokers not only for the characteristics related to smoking but also the onsets of carotid plaque. Surface morphology was also efficiently detected by ultrasonography. Further ridge trace analysis showed that ultrasonography is efficient for diagnosis of calcified plaque compared with gold standard for plaque diagnosis. Further correlation analysis showed that ultrasonography parameters could offer reliable evidence for plaque scores, which was associated with age index. Ultrasonography parameters could efficiently differentiate plaque morphologies among enrolled smokers and never-smokers. CONCLUSION: Current smoking was positively associated with plaque calcification onsets, and smoking cessation could efficiently attenuate such injury. High-frequency ultrasound can clearly distinguish the details of calcification with promising clinical significance for current smoking patients.

Correlation Between Calcification Characteristics of Carotid Atherosclerotic Plaque and Plaque Vulnerability.

PURPOSE: To investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH). METHODS: Patients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery. RESULTS: A total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49-8.61; P = 0.004). CONCLUSION: Calcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.

Ancient Xinjiang mitogenomes reveal intense admixture with high genetic diversity.

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.

Maternal genetic structure in ancient Shandong between 9500 and 1800 years ago.

Archaeological and ancient DNA studies revealed that Shandong, a multi-culture center in northern coastal China, was home to ancient populations having ancestry related to both northern and southern East Asian populations. However, the limited temporal and geographical range of previous studies have been insufficient to describe the population history of this region in greater detail. Here, we report the analysis of 86 complete mitochondrial genomes from the remains of 9500 to 1800-year-old humans from 12 archaeological sites across Shandong. For samples older than 4600 years before present (BP), we found haplogroups D4, D5, B4c1, and B5b2, which are observed in present-day northern and southern East Asians. For samples younger than 4600 BP, haplogroups C (C7a1 and C7b), M9 (M9a1), and F (F1a1, F2a, and F4a1) begin to appear, indicating changes in the Shandong maternal genetic structure starting from the beginning of the Longshan cultural period. Within Shandong, the genetic exchange is possible between the coastal and inland regions after 3100 BP. We also discovered the B5b2 lineage in Shandong populations, with the oldest Bianbian individual likely related to the ancestors of some East Asians and North Asians. By reconstructing a maternal genetic structure of Shandong populations, we provide greater resolution of the population dynamics of the northern coastal East Asia over the past nine thousand years.

Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia.

Schizophrenia is a serious neuropsychiatric disorder, yet a clear pathophysiology has not been identified. To date, neither the objective biomarkers for diagnosis nor specific medications for the treatment of schizophrenia are clinically satisfactory. It is well accepted that lipids are essential to maintain the normal structure and function of neurons in the brain and that abnormalities in neuronal lipids are associated with abnormal neurodevelopment in schizophrenia. However, lipids and lipid-like molecules have been largely unexplored in contrast to proteins and their genes in schizophrenia. Compared with the gene- and protein-centric approaches, lipidomics is a recently emerged and rapidly evolving research field with particular importance for the study of neuropsychiatric disorders such as schizophrenia, in which even subtle aberrant alterations in the lipid composition and concentration of the neurons may disrupt brain functioning. In this review, we aimed to highlight the lipidomics of the brain, retina, and biofluids in both human and animal studies, discuss aberrant lipid alterations in correlation with schizophrenia, and propose future directions from the biological landscape towards potential clinical applications in schizophrenia. Recent studies are in support of the concept that aberrations in some lipid species [e.g. phospholipids, polyunsaturated fatty acids (PUFAs)] lead to structural alterations and, in turn, impairments in the biological function of membrane-bound proteins, the disruption of cell signaling molecule accessibility, and the dysfunction of neurotransmitter systems. In addition, abnormal lipidome alterations in biofluids are linked to schizophrenia, and thus they hold promise in the discovery of biomarkers for the diagnosis of schizophrenia.

Correlation between risk factors of cerebrovascular disease and calcified plaque characteristics in patients with atherosclerotic severe carotid stenosis.

Objectives: The aim of this study was to evaluate the relationship between the risk factors of cerebral vascular diseases (CVD) and the characteristics of calcified plaques in patients with severe carotid arteriosclerosis stenosis (SCAS).Methods: A total of 402 patients with SCAS who were treated in our hospital between January to December 2016 were included in this study. The patients were divided into calcified plaque group and non-calcified plaque group according to the ultrasonography and computerized tomography angiography (CTA) or digital subtraction angiography (DSA) imaging of SCAS-responsible plaque and the characteristics of calcified plaques evaluated by high-frequency ultrasound.Results: The patients with long-term diabetes mellitus or higher levels of fasting blood glucose were more likely to develop calcified plaques (P = 0.00 and P = 0.021, respectively). In addition, the patients with calcified plaques were mostly smokers (P = 0.016). Their smoking duration and accumulative smoking exposure were higher than those without calcified plaque (P = 0.006 and P = 0.007, respectively). The basal location of calcification (P = 0.004) and the type of patchy calcification (P = 0.00) were both easier to appear in smokers, while non-smokers were more likely to have small granular calcification (P = 0.002). Furthermore, the carotid plaque calcification with mixed-location were more frequently seen in patients with hypertension (P = 0.016). The risk factors independently associated with plaque calcification were significantly associated with smoking status, smoking age, and accumulative smoking exposure, as well as age and diabetes mellitus (all P < 0.05).Conclusion: Smoking, diabetes mellitus and age were independent risk factors for carotid plaque calcification. Smoking and hypertension were associated with specific locations and types of plaque calcification.

Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders.

Neuropsychiatric disorders represent a set of severe and complex mental illnesses, and the exact etiologies of which are unknown. It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders. Currently, the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment, because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure. In recent years, there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs. In the brain, circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts. They are highly active at neuronal synapses. These features make circRNAs uniquely crucial for understanding brain health, disease, and neuropsychiatric disorders. This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders. In addition, we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders. The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer.

Despite decades of research and major efforts, malignant brain tumors remain among the deadliest of all cancers. Recently, an increasing number of psychiatric drugs has been proven to possess suppressing activities against brain tumors, and rapid progress has been made in understanding the potential mechanisms of action of these drugs. In particular, the traditional mood stabilizer valproic acid, the widely used antidepressants fluoxetine and escitalopram oxalate, and the atypical psychiatric drug aripiprazole have demonstrated promise for application in brain tumor treatment strategies through multiple lines of laboratory, preclinical, and clinical evidence. The unexpected discovery of the anticancer properties of these drugs has ignited interest in the repurposing of other psychiatric drugs to combat brain cancer. In this review, we synthesize recent progress in understanding the potential molecular mechanisms underlying the brain cancer-killing activities of representative psychiatric drugs. We also identify key limitations in the repurposing of these medications that must be overcome to enhance our ability to successfully prevent and treat brain cancer, especially in the most vulnerable groups of patients, such as children and adolescents, pregnant women, and those with unfavorable genetic variants. Moreover, we propose perspectives that may guide future research and provide long-awaited new hope to patients with brain cancer and their families.

Antipsychotic drugs and sudden cardiac death: A literature review of the challenges in the prediction, management, and future steps.

Sudden cardiac death (SCD) is relatively uncommon, yet it is a deadly consequence of some antipsychotic medications in patients with psychiatric disorders. The widespread concerns about the adverse cardiac effects associated with antipsychotics and their unpredictable nature have led to a restriction on the use of some antipsychotic medications. Recent progress has been made in the identification of important genetic factors that may contribute to the adverse complication of antipsychotic drugs, suggesting that high-risk individuals can be identified prior to initiating therapy. In addition, some high-tech smart wearable medical devices have recently been developed, allowing users to record and analyze the electrocardiogram (ECG) in couple with artificial intelligence (AI) technologies, and notifying of irregular heart rhythms or arrhythmias, a medical condition well documented in most SCD cases. In this literature review, we summarize recent advances in understanding the link between SCD and antipsychotic drug usage, as well as in utilizing wearable medical devices for monitoring of cardiac arrhythmias. New strategies for improving the care of patients receiving antipsychotic medications are proposed. As it is now possible to evaluate the risk of SCD in patients on antipsychotic medications, preventative measures and close monitoring may be used to detect the early signs of adverse cardiac events and SCD.

The genomics of schizophrenia: Shortcomings and solutions.

Due to recent advances in human genomic technologies, there have been explosive interests and extensive research on the genomics of schizophrenia, a severe psychiatric disorder characterized by social cognitive deficits, hallucinations, and delusions. These new technologies, including next-generation sequencing (NGS), genome-wide association studies (GWAS), and the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) genome editing platform are capable of interrogating and editing the genome directly. In the past few years, these efforts have led to the identification of important loci and genes susceptible to schizophrenia. The findings have increased our understanding of the underlying genetic causes of schizophrenia and aided in the development of new approaches for more effectively diagnosing and treating schizophrenia. Despite the substantial progress, there are several unanswered questions about the genomics of schizophrenia, and there are a number of potential shortcomings in the current literature considering the complexity of the disease and limits of the current technologies. In the present review, we assessed the existing literature on the genomics of schizophrenia, identifying the strengths and study design shortcomings from the following aspects: elucidation of the pathogenesis, early risk prediction and diagnosis, and the treatment of schizophrenia. Moreover, we have proposed solutions to overcome the shortcomings of past studies. Lastly, we have discussed the importance of developing multidisciplinary teams and global research groups in order to improve the lives of schizophrenic patients globally.

Potential Value of Genomic Copy Number Variations in Schizophrenia.

Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs) are one of the main forms of genomic variations, ubiquitously occurring in the human genome. An increasing number of studies have shown that CNVs account for population diversity and genetically related diseases, including schizophrenia. The last decade has witnessed rapid advances in the development of novel genomic technologies, which have led to the identification of schizophrenia-associated CNVs, insight into the roles of the affected genes in their intervals in schizophrenia, and successful manipulation of the target CNVs. In this review, we focus on the recent discoveries of important CNVs that are associated with schizophrenia and outline the potential values that the study of CNVs will bring to the areas of schizophrenia research, diagnosis, and therapy. Furthermore, with the help of the novel genetic tool known as the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) system, the pathogenic CNVs as genomic defects could be corrected. In conclusion, the recent novel findings of schizophrenia-associated CNVs offer an exciting opportunity for schizophrenia research to decipher the pathological mechanisms underlying the onset and development of schizophrenia as well as to provide potential clinical applications in genetic counseling, diagnosis, and therapy for this complex mental disease.

Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection.

Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca2+]i signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle.

Genomic Editing of Non-Coding RNA Genes with CRISPR/Cas9 Ushers in a Potential Novel Approach to Study and Treat Schizophrenia.

Schizophrenia is a genetically related mental illness, in which the majority of genetic alterations occur in the non-coding regions of the human genome. In the past decade, a growing number of regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified to be strongly associated with schizophrenia. However, the studies of these ncRNAs in the pathophysiology of schizophrenia and the reverting of their genetic defects in restoration of the normal phenotype have been hampered by insufficient technology to manipulate these ncRNA genes effectively as well as a lack of appropriate animal models. Most recently, a revolutionary gene editing technology known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9; CRISPR/Cas9) has been developed that enable researchers to overcome these challenges. In this review article, we mainly focus on the schizophrenia-related ncRNAs and the use of CRISPR/Cas9-mediated editing on the non-coding regions of the genomic DNA in proving causal relationship between the genetic defects and the pathophysiology of schizophrenia. We subsequently discuss the potential of translating this advanced technology into a clinical therapy for schizophrenia, although the CRISPR/Cas9 technology is currently still in its infancy and immature to put into use in the treatment of diseases. Furthermore, we suggest strategies to accelerate the pace from the bench to the bedside. This review describes the application of the powerful and feasible CRISPR/Cas9 technology to manipulate schizophrenia-associated ncRNA genes. This technology could help researchers tackle this complex health problem and perhaps other genetically related mental disorders due to the overlapping genetic alterations of schizophrenia with other mental illnesses.

Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma: dysregulation and implications for early detection, diagnosis and therapy.

Hepatitis C virus (HCV) infection is one of main causes of hepatocellular carcinoma (HCC) and the prevalence of HCV-associated HCC is on the rise worldwide. It is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C, and to identify target molecules for the prevention and treatment of HCV-associated-HCC. Small non-coding RNAs, mainly microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) with size greater than 200 nucleotides, are likely to play important roles in a variety of biological processes, including development and progression of HCC. For the most part their underlying mechanisms of action remain largely unknown. In recent years, with the advance of high-resolution of microarray and application of next generation sequencing techniques, a significant number of non-coding RNAs (ncRNAs) associated with HCC, particularly caused by HCV infection, have been found to be differentially expressed and to be involved in pathogenesis of HCV-associated HCC. In this review, we focus on recent studies of ncRNAs, especially miRNAs and lncRNAs related to HCV-induced HCC. We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection, diagnosis and therapy of HCV-associated HCC. We also discuss the limitations of recent studies, and suggest future directions for research in the field. miRNAs, lncRNAs and their target genes may represent new candidate molecules for the prevention, diagnosis and treatment of HCC in patients with HCV infection. Studies of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.