The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

Emerging role of galectin 3 in neuroinflammation and neurodegeneration

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

On the thermodynamics of plasticity during quasi-isentropic compression of metallic glass

Entropy production in quasi-isentropic compression (QIC) is critically important for understanding the properties of materials under extremeconditions. However, the origin and accurate quantification of entropy in this situation remain long-standing challenges. In this work, a framework is established for the quantification of entropy production and partition, and their relation to microstructural change in QIC. Cu50Zr50is taken as a model material, and its compression is simulated by molecular dynamics. On the basis of atomistic simulation-informed physicalproperties and free energy, the thermodynamic path is recovered, and the entropy production and its relation to microstructural change aresuccessfully quantified by the proposed framework. Contrary to intuition, entropy production during QIC of metallic glasses is relativelyinsensitive to the strain rate ˙γ when ˙γ ranges from 7.5 × 10^(8) to 2 × 10^(9)/s, which are values reachable in QIC experiments, with a magnitudeof the order of 10^(−2)kB/atom per GPa. However, when ˙γ is extremely high (>2 × 10^(9)/s), a notable increase in entropy production rate with˙γ is observed. The Taylor–Quinney factor is found to vary with strain but not with strain rate in the simulated regime. It is demonstrated thatentropy production is dominated by the configurational part, compared with the vibrational part. In the rate-insensitive regime, the increase inconfigurational entropy exhibits a linear relation to the Shannon-entropic quantification of microstructural change, and a stretched exponential relation to the Taylor–Quinney factor. The quantification of entropy is expected to provide thermodynamic insights into the fundamentalrelation between microstructure evolution and plastic dissipation.

cNPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes

BACKGROUND Diabetes mellitus type 2(T2DM)is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action.It has been affecting over 400 million people all over the world.AIM To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM.METHODS Receiver operating characteristic(ROC)curve analysis was used to conduct diagnostic markers.The expression level of genes was determined by reverse transcription-PCR as well as Western blot.Cell proliferation assays were performed by cell counting kit-8(CCK-8)tests.At last,T2DM mice underwent Roux-en-Y gastric bypass surgery.RESULTS We found that NPAS2 was significantly up-regulated in isletβcell apoptosis of T2DM.The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM.NPAS2 overexpression did increase the level of KANK1.In addition,the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells.At last,we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1.CONCLUSION This study demonstrated that NPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes,and it may be an underlying therapy target of T2DM.

Synthesis of plant-based biogenic jarosite nanoparticles using Azadirachta indica and Eucalyptus gunni leaf extracts and its application in Fenton degradation of dicamba

Bio-jarosite,an iron mineral synthesized biologically using bacteria,is a substitute for iron catalysts in the Fenton oxidation of organic pollutants.Iron nanocatalysts have been widely used as Fenton catalysts because they have a larger surface area than ordinary catalysts,are highly recyclable,and can be treated efficiently.This study aimed to explore the catalytic properties of bio-jarosite iron nanoparticles syn-thesized with green methods using two distinct plant species:Azadirachta indica and Eucalyptus gunni.The focus was on the degradation of dicamba via Fenton oxidation.The synthesized nanoparticles exhibited different particle size,shape,surface area,and chemical composition characteristics.Both particles were effective in removing dicamba,with removal efficiencies of 96.8%for A.indica bio-jarosite iron nano-particles(ABFeNPs)and 93.0%for E.gunni bio-jarosite iron nanoparticles(EBFeNPs)within 120 min of treatment.Increasing the catalyst dosage by 0.1 g/L resulted in 7.6%and 43.0%increases in the dicamba removal efficiency for EBFeNPs and ABFeNPs with rate constants of 0.025 min^(-1) and 0.023 min^(-1),respectively,confrming their catalytic roles.Additionally,the high efficiency of both catalysts was demonstrated through five consecutive cycles of linear pseudo-first-order Fenton oxidation reactions.

From liver to hormones:The endocrine consequences of cirrhosis

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

Modified TiO_(2)/In_(2)O_(3) heterojunction with efficient charge separation for visible-light-driven photocatalytic CO_(2) reduction to C_(2) product

Utilizing sunlight to convert CO_(2) into chemical fuels could address the greenhouse effect and fossil fuel crisis,Heterojunction structure catalysts with oxygen vacancy are attractive in the field of photocatalytic CO_(2) conversion.Herein,a modified TiO_(2)/In_(2)O_(3)(R-P2 5/In_(2)O_(3-x)) type Ⅱ heterojunction composite with oxygen vacancies is designed for photocatalytic CO_(2) reduction,which exhibits excellent CO_(2) reduction activity,with a C_(2) selectivity of 56.66%(in terms of R_(electron)).In situ Fourier-transform infrared spectroscopy(DRIFTS) and time-resolved photoluminescence(TR-PL) spectroscopy are used to reveal the intermediate formation of the photocatalytic mechanism and photogenerated electron lifetime,respectively.The experimental characterizations reveal that the R-P25/In_(2)O_(3-x) composite shows a remarkable behavior for coupling C-C bonds.Besides,efficient charge separation contributes to the improved CO_(2) conversion performance of photocatalysts.This work introduces a type Ⅱ heterojunction composite photocatalyst,which promotes understanding the CO_(2) reduction mechanisms on heterojunction composites and is valuable for the development of photocatalysts.

Prediction of sepsis within 24 hours at the triage stage in emergency departments using machine learning

BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to fi nd a light-weight,convenient prediction method through machine learning.METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation.RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the fi ve most important features were acuity,arrival transportation,age,shock index,and respiratory rate.CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

Enhanced Object Detection and Classification via Multi-Method Fusion

Advances in machine vision systems have revolutionized applications such as autonomous driving,robotic navigation,and augmented reality.Despite substantial progress,challenges persist,including dynamic backgrounds,occlusion,and limited labeled data.To address these challenges,we introduce a comprehensive methodology toenhance image classification and object detection accuracy.The proposed approach involves the integration ofmultiple methods in a complementary way.The process commences with the application of Gaussian filters tomitigate the impact of noise interference.These images are then processed for segmentation using Fuzzy C-Meanssegmentation in parallel with saliency mapping techniques to find the most prominent regions.The Binary RobustIndependent Elementary Features(BRIEF)characteristics are then extracted fromdata derived fromsaliency mapsand segmented images.For precise object separation,Oriented FAST and Rotated BRIEF(ORB)algorithms areemployed.Genetic Algorithms(GAs)are used to optimize Random Forest classifier parameters which lead toimproved performance.Our method stands out due to its comprehensive approach,adeptly addressing challengessuch as changing backdrops,occlusion,and limited labeled data concurrently.A significant enhancement hasbeen achieved by integrating Genetic Algorithms(GAs)to precisely optimize parameters.This minor adjustmentnot only boosts the uniqueness of our system but also amplifies its overall efficacy.The proposed methodologyhas demonstrated notable classification accuracies of 90.9%and 89.0%on the challenging Corel-1k and MSRCdatasets,respectively.Furthermore,detection accuracies of 87.2%and 86.6%have been attained.Although ourmethod performed well in both datasets it may face difficulties in real-world data especially where datasets havehighly complex backgrounds.Despite these limitations,GAintegration for parameter optimization shows a notablestrength in enhancing the overall adaptability and performance of our system.

Boosting High-Voltage Practical Lithium Metal Batteries with Tailored Additives

The lithium(Li)metal anode is widely regarded as an ideal anode material for high-energy-density batteries.However,uncontrolled Li dendrite growth often leads to unfavorable interfaces and low Coulombic efficiency(CE),limiting its broader application.Herein,an ether-based electrolyte(termed FGN-182)is formulated,exhibiting ultra-stable Li metal anodes through the incorporation of LiFSI and LiNO3 as dual salts.The synergistic effect of the dual salts facilitates the formation of a highly robust SEI film with fast Li+transport kinetics.Notably,Li||Cu half cells exhibit an average CE reaching up to 99.56%.In particular,pouch cells equipped with high-loading lithium cobalt oxide(LCO,3 mAh cm^(-2))cathodes,ultrathin Li chips(25μm),and lean electrolytes(5 g Ah-1)demonstrate outstanding cycling performance,retaining 80%capacity after 125 cycles.To address the gas issue in the cathode under high voltage,cathode additives 1,3,6-tricyanohexane is incorporated with FGN-182;the resulting high-voltage LCO||Li(4.4 V)pouch cells can cycle steadily over 93 cycles.This study demonstrates that,even with the use of ether-based electrolytes,it is possible to simultaneously achieve significant improvements in both high Li utilization and electrolyte tolerance to high voltage by exploring appropriate functional additives for both the cathode and anode.

A 10-year review and epidemiology of animal bite cases in Gerash city, south of Iran: A retrospective cross-sectional study

Objective:To determine the temporal trend and epidemiology of animal bite cases in Gerash City,Iran.Methods:This retrospective cross-sectional study analyzed 630 cases of people with animal bites between 2011 and 2021 in Gerash City.The collected data were analyzed using Chi-square test.Results:The mean age of victims was(30.9±17.5)years.80.54%Of victims were male,39.70%were self-employed,and 64.60%were adults(≥18 years).Most cases of bites occurred in 2019(91 cases),2020(74 cases)and 2021(87 cases),and most of the bites were related to the upper limbs(62.70%).Most of the wounds were superficial(78%),most of the biting animals were domestic animals(91.74%),and most of the victims had Iranian nationality(97.62%).Conclusions:Given the increasing trend of animal bites in Gerash City,health authorities should carry out basic measures such as education and awareness among the public,especially at-risk groups such as adult males.Additionally,since most cases of bites are due to dogs,it seems necessary to plan for vaccination of dogs,especially those with owners.

Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor:a randomized double-blind trial

Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LECs)and blood endothelial cells(BECs),were determined to identify patients who would benefit from this treatment.Methods:PD-L1 positivity in LECs,BECs,and tumor cells(TCs)was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450(PD-L1 antibody)alone or in combination with anlotinib in patients with non-small cell lung cancer.Progression-free survival(PFS)with different levels of PD-L1 expression was compared between the two groups.Results:Among 75 patients,the median PFS(mPFS)was longer in patients who received TQB2450 with anlotinib[10 and 12 mg(161 and 194 days,respectively)]than patients receiving TQB2450 alone(61 days)[hazard ratio(HR)_(10 mg)=0.390(95%confidence interval{CI},0.201–0.756),P=0.005;HR_(12 mg)=0.397(0.208–0.756),P=0.005].The results were similar among 58 patients with high PD-L1 expression in LECs and TCs[159 and 209 vs.82 days,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 mg)=0.369(0.174–0.784),P=0.009],and 53 patients with high PD-L1 expression in BECs and TCs[161 and 209 vs.41 days,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 mg)=0.340(0.159–0.727),P=0.005].No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Conclusions:Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs.Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs,which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

The Immense Impact of Reverse Edges on Large Hierarchical Networks

Hierarchical networks are frequently encountered in animal groups,gene networks,and artificial engineering systems such as multiple robots,unmanned vehicle systems,smart grids,wind farm networks,and so forth.The structure of a large directed hierarchical network is often strongly influenced by reverse edges from lower-to higher-level nodes,such as lagging birds’howl in a flock or the opinions of lowerlevel individuals feeding back to higher-level ones in a social group.This study reveals that,for most large-scale real hierarchical networks,the majority of the reverse edges do not affect the synchronization process of the entire network;the synchronization process is influenced only by a small part of these reverse edges along specific paths.More surprisingly,a single effective reverse edge can slow down the synchronization of a huge hierarchical network by over 60%.The effect of such edges depends not on the network size but only on the average in-degree of the involved subnetwork.The overwhelming majority of active reverse edges turn out to have some kind of“bunching”effect on the information flows of hierarchical networks,which slows down synchronization processes.This finding refines the current understanding of the role of reverse edges in many natural,social,and engineering hierarchical networks,which might be beneficial for precisely tuning the synchronization rhythms of these networks.Our study also proposes an effective way to attack a hierarchical network by adding a malicious reverse edge to it and provides some guidance for protecting a network by screening out the specific small proportion of vulnerable nodes.

Mercury Levels Assessment in the Population of Aby and Frambo Villages in the Vinicity of Aby Lagoon in Côte d’Ivoire (West Africa)

The Minamata Convention in the aim to protect human life and the environment, seeks to reduce mercury (Hg) by monitoring it concentrations in the environment. Artisanal and Small-scale Gold Mining (ASGM) has been identified as the most important anthropogenic source of human exposure to Hg. In this context, the main goal of this study was to assess the level of mercury in hair of two (2) populations living along two lagoons respectively Aby and Tendo, in Ivory Coast. To reach this goal, hair samples of 138 residents were collected and analyzed by using Cold Vapor Atomic Fluorescence Spectrophotometry (CV-AFS) technique for mercury concentration. Results showed that for the entire population the Hg mean was 2.34 μg/g. Also, they were ranged between 0.15 to 8.53 μg/g and presented substantial differences amongst the villages. In Aby village, we observed the highest Hg concentrations (Mean = 2.62 μg/g). Our findings showed that almost the entire sample group (82%) exceed the USEPA recommended limit, furthermore 56% of them exceed the normal level of WHO and 2% of the respondent has the unhealthy levels of mercury (≥6 μg Hg/g) of hair by WHO standards. Gender differences in hair mercury varies greatly among reports. Lower levels in women’s hair compared to men were reported in the both village. Considering age, the lowest concentrations were observed with children. However, when we take in account the age groups, data suggested that the most exposed sub-population of [18-29] years old is from Aby village in opposite at Frambo village, the same case those who were ≥ 40 years old. It’s convenient to note that, the proportion of Mercury levels would not to be neglected among studied population especially with the resident from Aby village. So, some measures need to be taken at the political level to control mercury contamination.

Molecular Detection of Pathogens Involved in Sexually Transmitted Infections in Brazzaville, Congo

The objective of this multicentric study was to assess the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma génitalium and Trichomonas vaginalis infections in Brazzaville, in the Republic of Congo, using molecular methods. From January to December 2021, the sexually transmitted disease risk participants were recruited from six centers: The Association of Young HIV-Positive People of Congo, The Congolese Association for Family Welfare, The Association for Support to Vulnerable Groups, Talangaï hospital, Brazzaville university hospital (outpatient service) and the private clinic COGEMO (outpatient service). The real-time multiplex PCR was carried out to detect these pathogens. Each patient had at least one specimen (urine, urethral, anal and/or vaginal samples). The patients were considered infected when one of their samples was positive. 287 participants made of 227 women and 60 men were tested. The general prevalence of these infections was: Chlamydia trachomatis 2.79%, Neisseria gonorrhoeae 3.14%, Mycoplasma génitalium 3.45% and Trichomonas vaginalis 2.97. The prevalence rates according to sex were: C. trachomatis, M. génitalium, N. gonorrhea and T. vaginalis were 1.32%, 2.05%, 1.32% and 3.42% in women and 8.33%, 7.02%, 10% and 1.75% in men, respectively. Most infected patients were asymptomatic. Prevalence rates were higher in bisexual individuals, with the exception of T. vaginalis which showed higher prevalence in heterosexual patients. The bisexual and homosexual individuals represent a major public health problem in sexually active young adults, particularly among men having sex with men. These sexually transmitted infections are mainly asymptomatic, their diagnosis and management remain difficult in developing countries.

Hydroxychloroquine-azithromycin,doubase C,and QTc prolongation in congolese patients with COVID-19:Myth or reality?

BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Western countries.In the DR Congo,few studies have evaluated the safety of this association or proposed new molecules.AIM To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C(new molecule).METHODS In present randomized clinical trial,we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C.Electrocardiogram(ECG)changes on day 14 of randomization were determined based on pretreatment tracing.Prolonged QTc was defined as≥500 ms on day 14 or an increase of≥80 ms compared to pretreatment tracing.Patients with cardiac disease,those undergoing other treatments likely to prolong QTc,and those with disturbed ECG tracings were excluded from the study.RESULTS The study included 258 patients(mean age 41±15 years;52%men;3.4%diabetics,11.1%hypertensive).Mild and moderate COVID-19 were found in 93.5%and 6.5%of patients,respectively.At baseline,all patients had normal sinus rhythm,a mean heart rate 78±13/min,mean PR space 170±28 ms,mean QRS 76±13 ms,and mean QTc 405±30 ms.No complaints suggesting cardiac involvement were reported during or after treatment.Only four patients(1.5%)experienced QTc interval prolongation beyond 500 ms.Similarly,only five patients(1.9%)had an increase in the QTc interval of more than 80 ms.QTc prolongation was more significant in younger patients,those with high viral load at baseline,and those receiving HCQ-AZI(P<0.05).None of the patients developed Tsd.CONCLUSION QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C.The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.

Extraterrestrial Life in the Thermosphere: Plasmas, UAP, Pre-Life, Fourth State of Matter

“Plasmas” up to a kilometer in size and behaving similarly to multicellular organisms have been filmed on 10 separate NASA space shuttle missions, over 200 miles above Earth within the thermosphere. These self-illuminated “plasmas” are attracted to and may “feed on” electromagnetic radiation. They have different morphologies: 1) cone, 2) cloud, 3) donut, 4) spherical-cylindrical;and have been filmed flying towards and descending from the thermosphere into thunderstorms;congregating by the hundreds and interacting with satellites generating electromagnetic activity;approaching the Space Shuttles. Computerized analysis of flight path trajectories documents these plasmas travel at different velocities from different directions and change their angle of trajectory making 45°, 90°, and 180° shifts and follow each other. They’ve been filmed accelerating, slowing down, stopping, congregating, engaging in “hunter-predatory” behavior and intersecting plasmas leaving a plasma dust trail in their wake. Similar life-like behaviors have been demonstrated by plasmas created experimentally. “Plasmas” may have been photographed in the 1940s by WWII pilots (identified as “Foo fighters”);repeatedly observed and filmed by astronauts and military pilots and classified as Unidentified Aerial—Anomalous Phenomenon. Plasmas are not biological but may represent a form of pre-life that via the incorporation of elements common in space, could result in the synthesis of RNA. Plasmas constitute a fourth state of matter, are attracted to electromagnetic activity, and when observed in the lower atmosphere likely account for many of the UFO-UAP sightings over the centuries.

Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment challenging.AIM To investigate the management of patients with visceral PCM admitted with EHC.METHODS All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated.Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and prognosis.Statistical analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact test.RESULTS Of 1645 patients diagnosed with PCM,40(2.4%)had EHC.Of these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between them.EHC recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group 2.The mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with no statistically significant difference.CONCLUSION Although PCM-related EHC is rare,it needs to be included in the differential diagnosis of malignancies,as timely treatment can prevent hepatic and extrahepatic sequelae.

肺癌T7噬菌体文库中MUC1蛋白抗原模拟表位的筛选

目的利用噬菌体表面展示技术,从肺癌T7噬菌体展示文库中筛选MUC1蛋白抗原的模拟表位。方法以MUC1单克隆抗体为靶分子,对肺癌T7噬菌体文库进行淘洗筛选,得到的阳性克隆进行测序并推导其氨基酸序列,对得到的阳性噬菌体克隆进行鉴定。结果经3轮淘选,得到20个阳性克隆。测序获得AAPDFRP、SAPDDRP 2种氨基酸序列,对MUC1单抗的抑制率均在50%以上,与肺癌血清结合特异性较高,此2种蛋白序列可模拟MUC1蛋白抗原表位。结论通过噬菌体展示技术成功筛选到MUC1蛋白的模拟表位序列XAPDXRP(X为任意氨基酸),对肺癌的早期诊断有一定的参考价值。