治疗相关神经内分泌前列腺癌机制研究与靶向治疗新进展

前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤,我国前列腺癌新发病例临床分期偏晚,Gleason级别较高,临床上多表现为进展期前列腺癌,已失去手术机会[1]。雄激素剥夺治疗(androgen deprivation therapy,ADT)是进展期前列腺癌的主要治疗手段,可显著抑制前列腺癌的进展,但是几乎所有患者在治疗12~18个月后进展为更具侵袭性的去势抵抗性前列腺癌(castration resistant prostate cancer,CRPC)[2]。

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.

Advancements in Photovoltaic Panel Fault Detection Techniques

This paper examines the progression and advancements in fault detection techniques for photovoltaic (PV) panels, a target for optimizing the efficiency and longevity of solar energy systems. As the adoption of PV technology grows, the need for effective fault detection strategies becomes increasingly paramount to maximize energy output and minimize operational downtimes of solar power systems. These approaches include the use of machine learning and deep learning methodologies to be able to detect the identified faults in PV technology. Here, we delve into how machine learning models, specifically kernel-based extreme learning machines and support vector machines, trained on current-voltage characteristic (I-V curve) data, provide information on fault identification. We explore deep learning approaches by taking models like EfficientNet-B0, which looks at infrared images of solar panels to detect subtle defects not visible to the human eye. We highlight the utilization of advanced image processing techniques and algorithms to exploit aerial imagery data, from Unmanned Aerial Vehicles (UAVs), for inspecting large solar installations. Some other techniques like DeepLabV3 , Feature Pyramid Networks (FPN), and U-Net will be detailed as such tools enable effective segmentation and anomaly detection in aerial panel images. Finally, we discuss implications of these technologies on labor costs, fault detection precision, and sustainability of PV installations.

Climate &Sustainability Implications of Land Use Alterations in an Urbanizing Region: Raleigh-Durham, North Carolina

Urban climate is the most immediate manifestation of the warming global climate for the majority of people on earth. Nearly half of those people live in small to medium sized cities, an understudied scale in urban climate research. Widespread characterization would be useful to decision makers in planning and design for land use decisions. Using a multi-method approach, the mesoscale UHI in the study region is characterized and the secular trend over the last sixty years evaluated. Under isolated ideal conditions the findings indicate a UHI of 5.3℃ ± 0.97℃ to be present in the study area, the magnitude of which is growing over time.

Flipped classroom approach to global outreach:cross-cultural teaching of horizontal strabismus to Chinese ophthalmology residents

AIM:To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.METHODS:Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018.Residents were instructed to watch a pre-class video lecture prior to the in-class-casebased activity.Content tests(5 Ophthalmic Knowledge Assessment Program style questions)and surveys were administered before and after the classroom sessions(100%response rate).These results were compared to that of an American cohort who were taught the same content.RESULTS:The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents(92%vs 55%,P=0.04)and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style(P-values between 0.008 and<0.001).In both Chinese and American cohorts,we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session(P=0.025 for Chinese residents;P=0.001 for US residents),whereas scores in both groups for the esotropia course did not significantly improve.CONCLUSION:This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting.The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge.Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings.Finally,the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19,although such a format requires further study.

利用微流控技术应对COVID-19和其他肺部疾病的全球挑战

1. Introduction Pulmonary diseases present one of the most severe threats to human society. Since late 2019, the coronavirus disease 2019(COVID-19) pandemic has significantly impacted the lifestyle, culture, and politics of almost everyone in the world. COVID-19 causes severe pulmonary dysfunction, which is a major cause of mortality for those affected [1].

Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates

Background:Infants undergoing cardiac surgery with cardiopulmonary bypass(CPB)frequently receive intraoperative methylprednisolone(MP)to suppress CPB-related inflammation;however,the optimal dosing strategy and efficacy of MP remain unclear.Methods:We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014–2017 at our institution.We combined real-world dosing data from the electronic health record(EHR)and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration(Cmax)and area under the concentration-time curve for 24 h(AUC24)for MP and the inflammatory cytokines interleukin-6(IL-6)and interleukin-10(IL-10).We evaluated the relationships between post-operative,safety,and other clinical outcomes obtained from the EHR with each predicted exposure using non-parametric tests.Results:A total of 142 infants with median post-natal age 8(interquartile range[IQR]:5,37)days received a total dose of 30(19,49)mg/kg of MP.Twelve(8%)died,37(26%)met the composite post-operative outcome,114(80%)met the composite safety outcome,and 23(16%)had a major complication.Predicted median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major complications.Predicted median Cmax and AUC24 MP exposure was significantly higher for infants requiring insulin.No exposure was associated with death or other safety outcomes.Conclusions:Pro-inflammatory IL-6,but not MP exposure,was associated with post-operative organ dysfunction,suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical outcomes.Prospective study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

Adaptive Design of Fluorescence Imaging Systems for Custom Resolution, Fields of View, and Geometries

Objective and Impact Statement:We developed a generalized computational approach to design uniform,high-intensity excitation light for low-cost,quantitative fluorescence imaging of in vitro,ex vivo,and in vivo samples with a single device.Introduction:Fluorescence imaging is a ubiquitous tool for biomedical applications.Researchers extensively modify existing systems for tissue imaging,increasing the time and effort needed for translational research and thick tissue imaging.These modifications are applicationspecific,requiring new designs to scale across sample types.Methods:We implemented a computational model to simulate light propagation from multiple sources.Using a global optimization algorithm and a custom cost function,we determined the spatial positioning of optical fibers to generate 2 illumination profiles.These results were implemented to image core needle biopsies,preclinical mammary tumors,or tumor-derived organoids.Samples were stained with molecular probes and imaged with uniform and nonuniform illumination.Results:Simulation results were faithfully translated to benchtop systems.We demonstrated that uniform illumination increased the reliability of intraimage analysis compared to nonuniform illumination and was concordant with traditional histological findings.The computational approach was used to optimize the illumination geometry for the purposes of imaging 3 different fluorophores through a mammary window chamber model.Illumination specifically designed for intravital tumor imaging generated higher image contrast compared to the case in which illumination originally optimized for biopsy images was used.Conclusion:We demonstrate the significance of using a computationally designed illumination for in vitro,ex vivo,and in vivo fluorescence imaging.Applicationspecific illumination increased the reliability of intraimage analysis and enhanced the local contrast of biological features.This approach is generalizable across light sources,biological applications,and detectors.

Feature identification in complex fluid flows by convolutional neural networks

Recent advancements have established machine learning's utility in predicting nonlinear fluid dynamics,with predictive accuracy being a central motivation for employing neural networks.However,the pattern recognition central to the networks function is equally valuable for enhancing our dynamical insight into the complex fluid dynamics.In this paper,a single-layer convolutional neural network(CNN)was trained to recognize three qualitatively different subsonic buffet flows(periodic,quasi-periodic and chaotic)over a high-incidence airfoil,and a near-perfect accuracy was obtained with only a small training dataset.The convolutional kernels and corresponding feature maps,developed by the model with no temporal information provided,identified large-scale coherent structures in agreement with those known to be associated with buffet flows.Sensitivity to hyperparameters including network architecture and convolutional kernel size was also explored.The coherent structures identified by these models enhance our dynamical understanding of subsonic buffet over high-incidence airfoils over a wide range of Reynolds numbers.

Electron Micrographic Representations of Mechanisms of Action of Murine Norovirus on ATCC TIB-71 Cells and Level of Gene Expression

Human noroviruses (HuNoV) are the number one cause of viral gastroenteritis worldwide resulting in a significant cause of morbidity and mortality in all age groups. However, despite the medical relevance of HuNoV, effective treatment against norovirus infection is yet to be developed. In this study, we investigated the anti-Noroviral activity of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) seeds using murine norovirus, a surrogate of human norovirus. The antiviral mechanisms of action were also examined using a gene expression studies and transmission electron microscopy. Our results showed that virus-infected cells were left potentially void of all the cell machineries whereas uninfected cells represent healthy normal and dividing cells. The infected treated cells with extracts showed restoration of the dense cytoplasm, cytoplasmic membrane, and the nucleus. These cells were also associated with the expression of ORF genes. This study demonstrates the antiviral properties of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) and thus indicates their potential as natural remedies to treat noroviruses.

Vestibular migraine in low-and lower-middle-income countries:A scoping review

Background:Vestibular migraine(VM)is a common cause of dizziness that is underrecognized,underdiagnosed,and challenging to effectively treat.The prevalence,appropriate diagnostic workup,and therapies for VM in low-and lower-middle-income countries(LLMICs)remain understudied.The objective of this scoping review is to evaluate the current state of VM research in LLMICs.Methods:PubMed,Embase,and Web of Science databases were searched to execute a scoping review of VM.Keywords“vestibular diseases”and“vertigo”were used in combination with terms referring to LLMICs as defined by the World Bank.Title and abstract screening,full-text review,and data collection were conducted by two authors independently.Results:Twenty-six studies were included in the scoping review.Most studies were cross-sectional(57.7%)or case studies/series(23.1%)and were conducted in urban settings only(92.3%).Geographic distribution of studies was skewed,with 65.4%of articles originating from India.The prevalence of VM among clinic patients ranged from 0.3%to 33.3%.VM most frequently presented as headache,nausea and vomiting,and photophobia.Radiographic imaging,audiometry,and electronystagmography/videonystagmography were the three most commonly utilized diagnostic modalities in the dizziness workup.The most studied pharmacotherapies included calcium channel blockers,followed by beta-blockers and antiepileptics.Case studies and series discussed less common VM pharmacotherapies,such as ayurvedic medicine.Conclusions:There is a need for more VM research in LLMICs,including innovative diagnostic approaches and therapies that can improve VM care globally.Equitable partnerships between LLMIC and highincome country researchers must expand vestibular research capacity and productivity in LLMICs.

Obesity is positively Associated with Depression in Older Adults:Role of Systemic Inflammation

Objective We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults.Methods Adults≥65 years old(n=1,973)were interviewed at baseline in 2018 and 1,459 were followed up in 2021.General and abdominal obesity were assessed,and serum C-reactive protein(CRP)levels were measured at baseline.Depression status was assessed at baseline and at follow-up.Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms,as well as the relationship between obesity and CRP levels.The associations of CRP levels with the geriatric depression scale,as well as with its three dimensions,were investigated using multiple linear regressions.Results General obesity was associated with worsening depression symptoms and incident depression,with an odds ratio(OR)[95%confidence interval(CI)]of 1.53(1.13-2.12)and 1.80(1.23-2.63),especially among old male subjects,with OR(95%CI)of 2.12(1.25-3.58)and 2.24(1.22-4.11),respectively;however,no significant relationship was observed between abdominal obesity and depression.In addition,general obesity was associated with high levels of CRP,with OR(95%CI)of 2.58(1.75-3.81),especially in subjects free of depression at baseline,with OR(95%CI)of 3.15(1.97-5.04),and CRP levels were positively correlated with a score of specific dimension(life satisfaction)of depression,P<0.05.Conclusion General obesity,rather than abdominal obesity,was associated with worsening depressive symptoms and incident depression,which can be partly explained by the systemic inflammatory response,and the impact of obesity on depression should be taken more seriously in the older male population.

Barriers in the Transition of Care for Heart Failure Patients Attending Clinics in Mwanza City, Tanzania

Introduction: Transition of care strategies have shown to improve quality of lives of heart failure patients, but it has little implemented in clinical settings. Objective: To evaluate context-specific perceived barriers and experiences of heart failure patients during their admission and after they were discharged from hospital. Methods: A cross-sectional qualitative study was conducted among 13 heart failure patients at two large referral hospitals in northwestern Tanzania. In-depth interviews among heart failure patients, in line with the Consolidated Criteria for Reporting Qualitative research checklist, were used to collect data. Interviews were audio recorded, transcribed, and translated into English. Results: Three key barriers were identified, as well as possible solutions that could improve the transition of care for heart failure patients. These include strengthening healthcare provider communications, organizing medication management, and assisting with follow-up appointments. Conclusion: The barriers identified are real and challenging in clinical resource- limited settings. Findings suggest they can be overcome when realistic and tailor-made interventions are in place.

Automatic recognition of tweek atmospherics and plasma diagnostics in the lower ionosphere with the machine learning method

Tweek atmospherics are extremely low frequency and very low frequency pulse signals with frequency dispersion characteristics that originate from lightning discharges and that propagate in the Earth–ionosphere waveguide over long distances.In this study,we developed an automatic method to recognize tweek atmospherics and diagnose the lower ionosphere based on the machine learning method.The differences(automatic−manual)in each ionosphere parameter between the automatic method and the manual method were−0.07±2.73 km,0.03±0.92 cm^(−3),and 91±1,068 km for the ionospheric reflection height(h),equivalent electron densities at reflection heights(Ne),and propagation distance(d),respectively.Moreover,the automatic method is capable of recognizing higher harmonic tweek sferics.The evaluation results of the model suggest that the automatic method is a powerful tool for investigating the long-term variations in the lower ionosphere.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography

BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension(CTEPH),approximately 20%-29%of patients exhibit a restrictive pattern on pulmonary function testing.AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area(CSA)in patients with CTEPH.METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019,we evaluated 15 patients with CTEPH who had chest computed tomography(CT)performed at baseline and after at least 6 mo of therapy.We matched the CTEPH cohort with 45 control patients by age,sex,and observation period.CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.RESULTS Total,right lung,and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline(total,P=0.004;right lung,P=0.003;right lower lobe;P=0.01).In the CTEPH group,the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group(total,P=0.01;right lung,P=0.007;right lower lobe,P=0.01;CSA,P=0.0002).There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.CONCLUSION After at least 6 mo of treatment,CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

白令海楚科奇海的海冰范围变化特征

白令海和楚科奇海位于北极太平洋一侧的海冰外缘线附近,具有较强烈的气冰海相互作用.采用滑动t检验和小波分析方法对白令海和楚科奇海1953—2004年海冰范围的年际变化、年代际变化和总体趋势变化进行分析.结果表明:20世纪70年代后期,海冰范围在白令海存在显著的均值突变现象,而楚科奇海在对应阶段则表现为更明显的变频现象;在突变点前后两个时段里,阿留申低压中心低压加强、核心位置偏移以及对应风场分布的变化是导致白令海海冰范围明显缩小的主要动力原因.楚科奇海海冰范围的年际变化中存在由低频向高频变化的现象,该现象除了在局地气温变化中存在之外,在北冰洋区域风涡度、波弗特海纬向风、东西伯利亚海经向风等动力因素中也有所体现.因此,除热力因素外,动力因素引起的海冰的平流与该变频现象也存在一定的联系.

胞外Ca^(2+)信号——动植物中的第一信使

钙离子作为重要的胞内第二信使,控制着许多细胞的功能,人们对此已经研究得比较深入。然而最近发现的一些细胞表面胞外Ca2+探测器使我们想到是否在胞外环境中,钙离子也具有信号分子的功能。钙离子传感器包括已经研究得比较清楚的胞外Ca2+敏感受体—最初从甲状旁腺分离的G-耦联蛋白受体(CaR),另外,还有其他受体、通道和膜蛋白也都对胞外[Ca2+]的变化很敏感。最近从拟南芥保卫细胞中克隆到一个胞外钙离子受体蛋白(CAS),通过胞外钙离子的变化引起胞内钙离子信号。这些受体蛋白的克隆,使人们确信Ca2+在细胞中可以发挥第一信使的功能。

一氧化氮在植物中的信号分子功能研究:进展和展望

一氧化氮(NO)是一种生物活性分子,越来越多的证据表明它是生物体内分布最为广泛的信号分子之一.NO作为植物生长发育的一个关键调节因子,能对各种生物或非生物胁迫产生应答,在植物生长发育与环境互作的协调过程中起着中枢性的作用.近年来,对于一氧化氮在植物中分子功能的研究取得了较大进展,特别是其信号转导功能、对基因表达的调控和植物体内NO稳态平衡的维持等方面.文中较全面地介绍了植物体内NO的合成、功能、信号转导、对基因表达的调控以及植物体内NO动态平衡的维持等方面研究的进展,并对该领域今后的研究进行了展望.

植物保卫细胞离子通道在气孔运动中的作用

介绍保卫细胞质膜和液泡膜上的离子通道活性变化及其在气孔运动中的作用,同时对各种刺激引发气孔运动过程中的信使Ca2+、H2O2和pH等对离子通道的调节作用作了概述。

电磁致热超声系统设计及基于小波阈值去噪方法的信号处理

本文给出了一个电磁致热超声(EMITA)实验系统,针对实验信号的提取问题,首先研究了实验平台的改进方法,通过置入波导内容器截面的设计,增加微波透过率;对耦合液的选择研究,减小微波脉冲对超声波接收传感器的电磁冲击,从而提高系统在强电磁脉冲下的电磁兼容(EMC)能力;其次为了从低信噪比数据中有效提取EMITA超声信号,研究了应用小波分析方法和阈值去噪重构方法处理实验采集的EMITA信号.