The Changes of the U. S. and the Constraints It Facing

The war in Iraq is coming to an end, and the military actions are giving place to the reconstructions of that country’s political, economic and social systems. This war marks a major event in international

Antisense therapy:a potential breakthrough in the treatment of neurodegenerative diseases

Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

FREE SPEECH OR SINOPHOBIA? THE U.S. SENATE MUST DECIDE

The 100 men and women who make up the U.S.Senate will soon have an important choice.They will either affirm that the First Amendment matters or they will surrender to fear.The senators must decide whether to go along with their colleagues in the House of Representatives and require the popular social media app TikTok to be sold to an American company.If they do endorse the House vote,then ByteDance must divest itself of TikTok or see the app will be banned on U.S.-based social media platforms.

Determining Hubbard U of VO_(2) by the quasi-harmonic approximation

Vanadium dioxide VO_(2) is a strongly correlated material that undergoes a metal-to-insulator transition around 340 K.In order to describe the electron correlation effects in VO_(2), the DFT+U method is commonly employed in calculations.However, the choice of the Hubbard U parameter has been a subject of debate and its value has been reported over a wide range. In this paper, taking focus on the phase transition behavior of VO_(2), the Hubbard U parameter for vanadium oxide is determined by using the quasi-harmonic approximation(QHA). First-principles calculations demonstrate that the phase transition temperature can be modulated by varying the U values. The phase transition temperature can be well reproduced by the calculations using the Perdew–Burke–Ernzerhof functional combined with the U parameter of 1.5eV. Additionally,the calculated band structure, insulating or metallic properties, and phonon dispersion with this U value are in line with experimental observations. By employing the QHA to determine the Hubbard U parameter, this study provides valuable insights into the phase transition behavior of VO_(2). The findings highlight the importance of electron correlation effects in accurately describing the properties of this material. The agreement between the calculated results and experimental observations further validates the chosen U value and supports the use of the DFT+U method in studying VO_(2).

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone

With the increase in antimicrobial resistance,it has become necessary to explore alternative approaches for combating and preventing diseases.DB-cinnamaldehyde(CNM)and Benzyl4-amino(B4AM)are bioactive compounds derived from chalcones but with restricted solubility in aqueous media.Nanoemulsions can enhance the solubility of compounds and can be a promising alternative in the development of novel antimicrobials,with reduced side effects and prolonged release.The objective of this study was to evaluate the stability of oil-in-water nanoemulsions loaded with two distinct types of chalcones at two different dosages,to propose a stable formulation with antimicrobial properties.Results showed that nanoemulsions presented high encapsulation efficiency,low polydispersity index(PDI)and particle size below 200 nm,indicating that emulsification was a suitable method for nanoemulsion preparation.Nanoemulsions with higher dosages exhibited significant antimicrobial effects when compared to free chalcones and positive controls.Notably,B4AM nanoemulsions at higher dosages showed expressive activity against Salmonella minnesota,with a 420%greater inhibitory response compared to the free form and showing equivalence to the positive control.CNM nanoemulsions showed excellent inhibitory activity at the highest dosage,equivalent to the positive control against S.minnesota and Staphylococcus aureus.The greater number of conjugated bonds in CNM increased the antimicrobial activity in comparison with B4AM,and the formation of nanometric domains enhanced the bioavailability,being a promising alternative for antimicrobial applications.

Physiological and pathological functions of circular RNAs in the nervous system

Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.

Digital Disparities:How Artificial Intelligence Can Facilitate Anti-Black Racism in the U.S.Healthcare Sector

This paper delves into the intricate interplay between artificial intelligence(AI)systems and the perpetuation of Anti-Black racism within the United States medical industry.Despite the promising potential of AI to enhance healthcare outcomes and reduce disparities,there is a growing concern that these technologies may inadvertently/advertently exacerbate existing racial inequalities.Focusing specifically on the experiences of Black patients,this research investigates how the following AI components:medical algorithms,machine learning,and natural learning processes are contributing to the unequal distribution of medical resources,diagnosis,and health care treatment of those classified as Black.Furthermore,this review employs a multidisciplinary approach,combining insights from computer science,medical ethics,and social justice theory to analyze the mechanisms through which AI systems may encode and reinforce racial biases.By dissecting the three primary components of AI,this paper aims to present a clear understanding of how these technologies work,how they intersect,and how they may inherently perpetuate harmful stereotypes resulting in negligent outcomes for Black patients.Furthermore,this paper explores the ethical implications of deploying AI in healthcare settings and calls for increased transparency,accountability,and diversity in the development and implementation of these technologies.Finally,it is important that I prefer the following paper with a clear and concise definition of what I refer to as Anti-Black racism throughout the text.Therefore,I assert the following:Anti-Black racism refers to prejudice,discrimination,or antagonism directed against individuals or communities of African descent based on their race.It involves the belief in the inherent superiority of one race over another and the systemic and institutional practices that perpetuate inequality and disadvantage for Black people.Furthermore,I proclaim that this form of racism can be manifested in various ways,such as unequal access to opportunities,resources,education,employment,and fair treatment within social,economic,and political systems.It is also pertinent to acknowledge that Anti-Black racism is deeply rooted in historical and societal structures throughout the U.S.borders and beyond,leading to systemic disadvantages and disparities that impact the well-being and life chances of Black individuals and communities.Addressing Anti-Black racism involves recognizing and challenging both individual attitudes and systemic structures that contribute to discrimination and inequality.Efforts to combat Anti-Black racism include promoting awareness,education,advocacy for policy changes,and fostering a culture of inclusivity and equality.

Giant Brunner's gland hyperplasia of the duodenum successfully resected en bloc by endoscopic mucosal resection: A case report

BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case of large BGH treated with endoscopic mucosal resection(EMR).CASE SUMMARY An 83-year-old woman presented at our hospital with dizziness.Blood tests revealed severe anemia,esophagogastroduodenoscopy showed a 6.5 cm lesion protruding from the anterior wall of the duodenal bulb,and biopsy revealed the presence of glandular epithelium.Endoscopic ultrasonography(EUS)demonstr-ated relatively high echogenicity with a cystic component.The muscularis propria was slightly elevated at the base of the lesion.EMR was performed without complications.The formalin-fixed lesion size was 6 cm×3.5 cm×3 cm,showing nodular proliferation of non-dysplastic Brunner's glands compartmentalized by fibrous septa,confirming the diagnosis of BGH.Reports of EMR or hot snare polypectomy are rare for duodenal BGH>6 cm.In this case,the choice of EMR was made by obtaining information on the base of the lesion as well as on the internal characteristics through EUS.CONCLUSION Large duodenal lesions with good endoscopic maneuverability and no evident muscular layer involvement on EUS may be resectable via EMR.

Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson’s disease

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.

Examining the Use of Scott’s Formula and Link Expiration Time Metric for Vehicular Clustering

Implementing machine learning algorithms in the non-conducive environment of the vehicular network requires some adaptations due to the high computational complexity of these algorithms.K-clustering algorithms are simplistic,with fast performance and relative accuracy.However,their implementation depends on the initial selection of clusters number(K),the initial clusters’centers,and the clustering metric.This paper investigated using Scott’s histogram formula to estimate the K number and the Link Expiration Time(LET)as a clustering metric.Realistic traffic flows were considered for three maps,namely Highway,Traffic Light junction,and Roundabout junction,to study the effect of road layout on estimating the K number.A fast version of the PAM algorithm was used for clustering with a modification to reduce time complexity.The Affinity propagation algorithm sets the baseline for the estimated K number,and the Medoid Silhouette method is used to quantify the clustering.OMNET++,Veins,and SUMO were used to simulate the traffic,while the related algorithms were implemented in Python.The Scott’s formula estimation of the K number only matched the baseline when the road layout was simple.Moreover,the clustering algorithm required one iteration on average to converge when used with LET.

NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

Quantum Spin Exchange Interactions to Accelerate the Redox Kinetics in Li–S Batteries

Spin-engineering with electrocatalysts have been exploited to suppress the“shuttle effect”in Li–S batteries.Spin selec-tion,spin-dependent electron mobility and spin potentials in activation barriers can be optimized as quantum spin exchange interactions lead-ing to a significant reduction of the electronic repulsions in the orbitals of catalysts.Herein,we anchor the MgPc molecules on fluorinated carbon nanotubes(MgPc@FCNT),which exhibits the single active Mg sites with axial displacement.According to the density functional theory calculations,the electronic spin polarization in MgPc@FCNT not only increases the adsorption energy toward LiPSs intermediates but also facilitates the tunneling process of electron in Li–S batter-ies.As a result,the MgPc@FCNT provides an initial capacity of 6.1 mAh cm^(-2) even when the high sulfur loading is 4.5 mg cm^(-2),and still maintains 5.1 mAh cm^(-2) after 100 cycles.This work provides a new perspective to extend the main group single-atom catalysts enabling high-performance Li–S batteries.

Anatomic location of the first dorsal extensor compartment for surgical De-Quervain’s tenosynovitis release:A cadaveric study

BACKGROUND De-Quervain’s tenosynovitis is a disorder arising from the compression and irritation of the first dorsal extensor compartment of the wrist.Patients who fail conservative treatment modalities are candidates for surgical release.However,risks with surgery include damage to the superficial radial nerve and an incomplete release due to inadequate dissection.Currently,there is a paucity of literature demonstrating the exact anatomic location of the first dorsal extensor compartment in reference to surface anatomy.Thus,this cadaveric study was performed to determine the exact location of the first extensor compartment and to devise a reliable surgical incision to prevent complications.AIM To describe the location of the first dorsal compartment in relation to bony surface landmarks to create replicable surgical incisions.METHODS Six cadaveric forearms,including four left and two right forearm specimens were dissected.Dissections were performed by a single fellowship trained upper extremity orthopaedic surgeon.Distance of the first dorsal compartment from landmarks such as Lister’s tubercle,the wrist crease,and the radial styloid were calculated.Other variables studied included the presence of the superficial radial nerve overlying the first dorsal compartment,additional compartment subsheaths,number of abductor pollicis longus(APL)tendon slips,and the presence of a pseudo-retinaculum.RESULTS Distance from the radial most aspect of the wrist crease to the extensor retinaculum was 5.14 mm±0.80 mm.The distance from Lister’s tubercle to the distal aspect of the extensor retinaculum was 13.37 mm±2.94 mm.Lister’s tubercle to the start of the first dorsal compartment was 18.43 mm±2.01 mm.The radial styloid to the initial aspect of the extensor retinaculum measured 2.98 mm±0.99 mm.The retinaculum length longitudinally on average was 26.82 mm±3.34 mm.Four cadaveric forearms had separate extensor pollicis brevis compartments.The average number of APL tendon slips was three.A pseudo-retinaculum was present in four cadavers.Two cadavers had a superficial radial nerve that crossed over the first dorsal compartment and retinaculum proximally(7.03 mm and 13.36 mm).CONCLUSION An incision that measures 3 mm proximal from the radial styloid,2 cm radial from Lister’s tubercle,and 5 mm proximal from the radial wrist crease will safely place surgeons at the first dorsal compartment.

Spatio-temporal Variation Characteristics of Extreme Climate Events and Their Teleconnections to Large-scale Ocean-atmospheric Circulation Patterns in Huaihe River Basin,China During 1959–2019

Huaihe River Basin(HRB) is located in China’s north-south climatic transition zone,which is very sensitive to global climate change.Based on the daily maximum temperature,minimum temperature,and precipitation data of 40 meteorological stations and nine monthly large-scale ocean-atmospheric circulation indices data during 1959–2019,we present an assessment of the spatial and temporal variations of extreme temperature and precipitation events in the HRB using nine extreme climate indices,and analyze the teleconnection relationship between extreme climate indices and large-scale ocean-atmospheric circulation indices.The results show that warm extreme indices show a significant(P < 0.05) increasing trend,while cold extreme indices(except for cold spell duration) and diurnal temperature range(DTR) show a significant decreasing trend.Furthermore,all extreme temperature indices show significant mutations during 1959-2019.Spatially,a stronger warming trend occurs in eastern HRB than western HRB,while maximum 5-d precipitation(Rx5day) and rainstorm days(R25) show an increasing trend in the southern,central,and northwestern regions of HRB.Arctic oscillation(AO),Atlantic multidecadal oscillation(AMO),and East Atlantic/Western Russia(EA/WR) have a stronger correlation with extreme climate indices compared to other circulation indices.AO and AMO(EA/WR) exhibit a significant(P < 0.05) negative(positive)correlation with frost days and diurnal temperature range.Extreme warm events are strongly correlated with the variability of AMO and EA/WR in most parts of HRB,while extreme cold events are closely related to the variability of AO and AMO in eastern HRB.In contrast,AMO,AO,and EA/WR show limited impacts on extreme precipitation events in most parts of HRB.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.