Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Transition from a filamentary mode to a diffuse one with varying distance from needle to stream of an argon plasma jet

Plasma jet has extensive application potentials in various fields, which normally operates in a diffuse mode when helium is used as the working gas. However, when less expensive argon is used, the plasma jet often operates in a filamentary mode. Compared to the filamentary mode, the diffuse mode is more desirable for applications. Hence, many efforts have been exerted to accomplish the diffuse mode of the argon plasma jet. In this paper, a novel single-needle argon plasma jet is developed to obtain the diffuse mode. It is found that the plasma jet operates in the filamentary mode when the distance from the needle tip to the central line of the argon stream(d) is short. It transits to the diffuse mode with increasing d. For the diffuse mode, there is always one discharge pulse per voltage cycle, which initiates at the rising edge of the positive voltage. For comparison, the number of discharge pulse increases with an increase in the peak voltage for the filamentary mode. Fast photography reveals that the plasma plume in the filamentary mode results from a guided positive streamer,which propagates in the argon stream. However, the plume in the diffuse mode originates from a branched streamer, which propagates in the interfacial layer between the argon stream and the surrounding air. By optical emission spectroscopy,plasma parameters are investigated for the two discharge modes, which show a similar trend with increasing d. The diffuse mode has lower electron temperature, electron density, vibrational temperature, and gas temperature compared to the filamentary mode.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Simulation of the Ecosystem Productivity Responses to Aerosol Diffuse Radiation Fertilization Effects over the Pan-Arctic during 2001–19

The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.

A Multi-Task Deep Learning Framework for Simultaneous Detection of Thoracic Pathology through Image Classification

Thoracic diseases pose significant risks to an individual's chest health and are among the most perilous medical diseases. They can impact either one or both lungs, which leads to a severe impairment of a person’s ability to breathe normally. Some notable examples of such diseases encompass pneumonia, lung cancer, coronavirus disease 2019 (COVID-19), tuberculosis, and chronic obstructive pulmonary disease (COPD). Consequently, early and precise detection of these diseases is paramount during the diagnostic process. Traditionally, the primary methods employed for the detection involve the use of X-ray imaging or computed tomography (CT) scans. Nevertheless, due to the scarcity of proficient radiologists and the inherent similarities between these diseases, the accuracy of detection can be compromised, leading to imprecise or erroneous results. To address this challenge, scientists have turned to computer-based solutions, aiming for swift and accurate diagnoses. The primary objective of this study is to develop two machine learning models, utilizing single-task and multi-task learning frameworks, to enhance classification accuracy. Within the multi-task learning architecture, two principal approaches exist soft parameter sharing and hard parameter sharing. Consequently, this research adopts a multi-task deep learning approach that leverages CNNs to achieve improved classification performance for the specified tasks. These tasks, focusing on pneumonia and COVID-19, are processed and learned simultaneously within a multi-task model. To assess the effectiveness of the trained model, it is rigorously validated using three different real-world datasets for training and testing.

基于Diffusers框架的电商产品图制作方法研究

基于Diffusers框架与Control Net网络,文章开发并实现了服装产品图的制作流程,将Segment Anything与Grounding DINO结合,实现了自动分割衣服蒙版。将Semantic Segmentation与ViTmatte结合,实现了对皮肤的精细化分割。文章使用大模型的低秩适应实现了对图像风格的微调,利用Ultralytics框架,结合Diffusers提出了一种图像修复方法。将生成图与原图对比,实验结果表明:将Diffusers与Control Net网络结合,能够实现模特替换与背景替换,该方法可以为用户提供衣服上身的参考,降低商家的产品图制作成本。

Expanding role and scope of artificial intelligence in the field of gastrointestinal pathology

Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.

InternDiffuseDet:结合可变形卷积和扩散模型的目标检测方法

针对现有目标检测中存在的漏检和误检、特征提取能力有限、处理复杂场景时检测精度不高等问题,基于DiffusionDet进行改进,提出了一种结合可变形卷积和扩散模型的目标检测方法。以模型在进入检测头之前需要更多且优质的特征图为核心思想,在主干网络中引入InternImage和DCNv3可变形卷积算子提升模型的感受野和非线性建模能力。对中间层的FPN特征金字塔进行改进,设计了一种基于选择性加权的特征金字塔CS-FPN;利用深度可分离卷积实现通道和区域的分离,同时采用CARAFE算子替代传统的上采样操作,提高分辨率和语义信息的传递;随后利用SGE注意力机制对特征图进行重组,以确保特征图在扩散的过程中保留更多的层次化信息。在特征图进入检测头之前,进行DDIM的扩散操作,获得不同时刻的特征图,以扩充检测特征图的数量。最后在目标框匹配和损失函数方面采用EIOU算法以处理目标框之间的位置偏移和尺度差异。实验数据显示,在COCO数据集和道路检测数据集上,改进后的模型在相同的实验环境下比原有模型分别提升了3.8和3.6个百分点。实验结果表明该方法在提高目标检测的准确性和鲁棒性方面具有一定的潜力,并为解决现实场景中的目标检测问题提供了新的思路和方法。

Molecular Pathology of Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer is a rare, autosomal dominant hereditary cancer syndrome associated with germline mutations in CDH1 in which 60% - 80% of affected individuals develop advanced diffuse gastric cancer, many as young adults. At clinical presentation, ~90% of these malignancies represent advanced, surgically incurable disease. As such, presymptomatic identification of germline CDH1 mutation carriers followed by early prophylactic total gastrictomy is the sole effective management strategy available. DNA sequence analysis of the CDH1 gene to identify the affected germline allele is the diagnostic standard of care;however, CDH1’s relatively high frequency of polymorphisms and the limited amount of experience available regarding them dictate that many identified variants are, as yet, of unknown clinical significance. Given the dramatic consequences of inappropriately offered or withheld treatment, careful clinical selection of at-risk individuals is critical. To facilitate this, multiple groups have published screening criteria recommendations, and while there is disagreement regarding the optimal diagnostic approach, the most widely-used overlap to a considerable degree.

Application of Optical Methods in Blood Studies upon Evaluation of Severity Rate of Diffuse Liver Pathology

Possible early diagnostic application of optical methods (dielectrophoresis, spectral and imaging ellipsometry, Fourier-transform infrared spectroscopy, Raman spectroscopy) in studies of red blood cells and serum of patients with diffuse liver disease with varying degrees of fibrosis has been evaluated. Application of combined optical methods was confirmed to significantly improve the performance of sensitivity, specificity, and accuracy index as well as to achieve the reliable results in diagnosis of both severe fibrosis and slight ulterior liver fibrosis. Identified diagnostic potential of optical methods can be effectively utilized in noninvasive screening evaluation of stages of diffuse liver disease of various geneses.

Does the intracoronary pressure differ according to two types(diffuse or focal)of coronary spasm?

BACKGROUND Several reports show that two types of coronary vasospasm(diffuse and focal spasm)are associated with the severity or prognosis of coronary spasm in patients with vasospastic angina(VSA).It is unclear whether intracoronary pressure differs between the two spasm types.AIM To investigate such relationships using a pressure wire during the spasm provocation test(SPT)in patients with VSA.METHODS Eighty-seven patients with VSA(average age:67 years;50 men,37 women)underwent SPT.During the SPT,a pressure wire was advanced into the distal portion of the right coronary artery and left anterior descending coronary artery,and the ratio of the intracoronary pressure to the aortic pressure(Pd/Pa)was continuously monitored.An SPT was performed using acetylcholine(ACh),and the presence of coronary spasm was defined as the presence of>90%arterial narrowing in response to an ACh infusion,with the usual chest symptoms and/or ischemic ECG changes.Focal spasm was defined as total or subtotal spasm within one segment of the AHA classification,while diffuse spasm was defined as>90%spasm with two or more segments.RESULTS Among 87 patients,the frequencies of metabolic syndrome and having coronary atherosclerosis were higher in the focal group(n=33)than in the diffuse spasm group(n=54,P<0.05).In the vessel analyses,in these 134 spastic segments,diffuse and focal spasms were detected in 100 and 34 vessels,respectively.The Pd/Pa at baseline was similar in both groups(diffuse:0.96±0.05,focal:0.95±0.05,P=0.35);however,the Pd/Pa during coronary spasm was lower in focal spastic vessels(0.66±0.20)than in diffuse spastic vessels(0.76±0.11,P<0.01),and the reduction in Pd/Pa during an SPT was also lower in focal spastic vessels(-0.29±0.20)than in diffuse spastic vessels(-0.18±0.11,P<0.01).The presence of focal spasm was a significant factor responsible for reduction in Pd/Pa during SPT.CONCLUSION These findings suggest that focal spasm may be more severe than diffuse spasm,judging from the intracoronary pressure during coronary spasm.

Axial length,vitreoretinal pathology,and anterior chamber depth can predict postoperative refractive outcomes in phacovitrectomy/silicone oil removal

AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.METHODS:The study is a retrospective,case-series study.Totally 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were enrolled.Eligible individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal pathology.The outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 D.RESULTS:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 D.There was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive outcome.In multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P<0.01).Univariate analysis revealed that longer eyes(AL>26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic PE.CONCLUSION:RD patients have the least favorable refractive outcome.AL,vitreoretinal pathology,and ACD are strongly associated with PE in the combined surgery.These three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.

基于Stable Diffusion的虚拟人形象预设计的应用与研究

对当前AIGC在虚拟形象预设计方面的现状及影响进行了分析和探讨。以Stable Diffusion为例,详细介绍了工程构建和实现,对相关模块的作用、运行环境、使用方法及其指令等多个方面进行了综合叙述、分析和探讨,针对使用不同采样方法、不同采样参数及不同训练模型生成图片效果的优劣进行了说明及展示。随后,通过项目实例,完整地展示了人物形象预设计的过程。最后,对AIGC等新技术可能带来的社会影响进行了预测和总结。

Aquaporin 5 in Alzheimer’s disease:a link between oral and brain pathology?

The involvement of aquaporins(AQPs)in the development of diseases has been widely described(Azad et al.,2021).AQP5 has been described in astrocytes changing after traumatic brain injuries(Chai et al.,2013),but the precise role of AQP5 in Alzheimer’s disease(AD)pathology is yet to be understood.We have recently reported that AQP5 expression changes during the development of AD(Antequera et al.,2022).The AQP5 expression in salivary glands is decreased in 6-month-old APP/PS1 mice and AD patients.This decrease in AQP5 expression could be involved in the mechanism of salivary gland dysfunction described in a previous study(Antequera et al.,2021).Now,we propose a new indirect role of AQP5 in the connection between infection-induced oral dysbiosis and AD(Sureda et al.,2020).Here,we suggest that the proinflammatory response induced by oral pathogen infection results in the downregulation of AQP5 contributing to the salivary gland secretory dysfunction.All these alterations destabilize the peripheral immune-inflammatory balance and exacerbate neuroinflammation and neurodegeneration leading to AD pathology.

Diffuse arterial atherosclerosis presenting with acute ischemic gastritis: A case report

BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.

Effects of alendronate on bone mass and organ pathology in ovariectomized mice

Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sham),ovariectomized group(OVX)and ovariectomized+alendronate group(ALN).The sodium alendronate was injected subcutaneously at 400μg/kg twice a week in the ALN group.The equal volume of normal saline was injected subcutaneously twice a week in the SHAM group and OVX group.After 12 weeks of drug administration,the samples were taken.The organ coefficients,main organ pathological sections,and bone histopathological sections were observed,and the micro CT,L4 biomechanics and serum biochemical indicators were analyzed.Results:The uterine coefficient of Sham group was(0.0054±0.0007)significantly higher than that of OVX group(0.0026±0.0009)and ALN group(0.0025±0.0007),and the difference was statistically significant(P<0.05).No obvious lesions or toxic or side effects were observed in the main organs.Compared with the OVX group,the ALN group with decalcified sections of bone tissue had compact trabecular structure and fewer adipocytes.Micro-CT results showed that the Tb.BMD,Tb.N,Tb.Th and Tb.BV/TV values of the ALN group were significantly increased compared with those of the OVX group,but the Tb.Sp value was significantly decreased,and the difference was statistically significant(P<0.05).In L4 vertebral body biomechanics,the elastic modulus(50.29±13.43)and maximum load number(29.83±4.92)of ALN group were significantly higher than those of OVX group(14.77±3.12)and maximum load number(11.57±3.18),and the difference was statistically significant(P<0.05).Compared with the OVX group,the serum OCN and PINP indicators of bone formation in the ALN group were increased,while the bone resorption indicators TRACP-5b and CTX-I were decreased,with statistical significance(P<0.05).Conclusion:Alendronate sodium improves bone quality by increasing bone density,improving bone microstructure,increasing bone strength,promoting bone formation and inhibiting bone resorption,without obvious toxic and side effects on organs.

Does Diffuse Circumnuclear Gas around Sgr A^(*) Achieve Collisional Ionization Equilibrium or Remain Non-equilibrium Ionization?

The feeding and feedback processes at the vicinity of a supermassive black hole(BH)are essential for our understanding of the connection between supermassive BH and its host galaxy.In this work,we provide a detailed investigation,both observational and theoretical,on the diffuse(~2"-20",~0.08-0.8 pc)X-ray emission around Sgr A*.Over two-decade Chandra observations are gathered to obtain highest signal-to-noise to date.We find that,the line center of iron lines of the outer 8"-18"region,ε_(c)=6.65+0.02-0.03 keV,is comparable to that(ε_(c)=6.60+0.05-0.03 keV)of the inner 2"-5"region.This is somewhat unexpected,since the gas temperature decreases further away from the central BH.Based on a dynamical inflow-outflow model that considers the gas feeding by stellar winds from Wolf-Rayet stars,we calculate the X-ray spectrum based on both the conventional collisional ionization equilibrium(CIE)assumption,and the newly developed non-equilibrium ionization(NEI)assumption.We find that,theoretically gases within~8"-10"remain in a CIE state,outside of this radius they will be in the NEI state.A comparison of the properties of~6.6 keV iron lines between CIE and NEI is addressed.Interestingly,the NEI interpretation of outer region is supported by the Chandra line center ε_(c) measurements of this region.

Dihydroartemisinin enhances cell apoptosis in diffuse large B cell lymphoma by inhibiting the STAT3 activity

Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.