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Aggregation of the tau protein is thought to be responsible for the neurodegeneration and subsequent functional impairments in diseases that are collectively named tauopathies. Alzheimer's disease is the most common tauopathy, but the group consists of over 20 different diseases, many of which have tau pathology as their primary feature. The development of tau therapies has mainly focused on preventing the formation of and/or clearing these aggregates. Of these, immunotherapies that aim to either elicit endogenous tau antibodies or deliver exogenous ones are the most common approach in clinical trials. While their mechanism of action can involve several pathways, both extra- and intracellular, pharmaceutical companies have primarily focused on antibody-mediated clearance of extracellular tau. As we have pointed out over the years, this is rather surprising because it is well known that most of pathological tau protein is found intracellularly. It has been repeatedly shown by several groups over the past decades that antibodies can enter neurons and that their cellular uptake can be enhanced by various means, particularly by altering their charge. Here, we will briefly describe the potential extra- and intracellular mechanisms involved in antibody-mediated clearance of tau pathology, discuss these in the context of recent failures of some of the tau antibody trials, and finally provide a brief overview of how the intracellular efficacy of tau antibodies can potentially be further improved by certain modifications that aim to enhance tau clearance via specific intracellular degradation pathways. [ABSTRACT FROM AUTHOR]

Painting is a two-dimensional visual language that expresses ideas and emotions while also creating aesthetic aspects. Flower and bird painting embodies an aesthetic ideal. For Chinese people, it serves as a harmonious coexistence with natural objects. Based on the contemporary context and the concept of environmental aesthetics, flower and bird painting should go beyond the sensual portrayal of plants and animals, individualistic lyricism, and the tendency of commercialization. It helps to examine the important value of plants and animals in the spiritual life of human beings from the perspective of the community of human destiny. It also raises the concern of contemporary people for the natural environment and the survival status of natural objects. Free from one's sorrow and happiness, the painting focuses on the pressing ecological issues of universal concern to all mankind and becomes art with world significance expressed in Chinese aesthetic symbols and artistic forms. It is important to classify the teaching resources of Chinese flower and bird painting theory and time. The traditional Chinese flower and bird painting theory and practice course teaching resources classification method are inefficient; for this reason, the adaptive clustering algorithm of teaching resources of Chinese flower and bird painting theory and practice is proposed. Using mutual information technology to obtain incremental data, the digital Chinese flower and bird painting theory and practice course teaching resources features are extracted. It features a tree to be constructed according to the two-step clustering algorithm. The leaf nodes of the feature tree are grouped according to the hierarchical coalescence algorithm. The Euclidean square distance is used to obtain the Chinese flower and bird painting theory and practice course teaching resources square root measure continuous variables. The number of clusters with the maximum growth distance represents the final number of clusters. The results show that the method can realize the effective grouping and classification of Chinese flower and bird painting theory and practice course teaching resources. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted imaging (DWI) can quantitatively reflect the diffusion characteristics of tissues, providing a theoretical basis for qualitative diagnosis and quantitative analysis of a disease. Purpose: To characterize testicular lesions that present as a hypointense signal on magnetic resonance imaging (MRI) T2-weighted images using DWI. Material and Methods: Study participants were divided into three groups. Group A were healthy controls (n = 35), group B included patients with mumps orchitis (n = 20), and group C included patients with seminoma (n = 15). DWI sequences used b-values of 0, 1000, and 2000 s/mm2. Apparent diffusion coefficient (ADC) values between 1000 and 2000 s/mm2 were calculated by MRI postprocessing software. The Kruskal–Wallis test and receiver operating characteristic analysis were performed to evaluate how well ADC values distinguished between mumps orchitis and seminoma. Results: Normal testicular tissue showed a hyperintense signal on DWI and hypointensity on the ADC map: mean ADC value was 0.77 (0.69–0.85) ± 0.08 ×10−3 mm2/s. Mumps orchitis and seminoma showed slight hyperintensity on DWI: mean ADC values were 0.85 (0.71–0.99) ± 0.15 ×10−3 mm2/s and 0.43 (0.39–0.47) ± 0.04 × 10−3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testicular tissue and seminoma and between mumps orchitis and seminoma. The cutoff ADC value for differentiating seminoma from mumps orchitis was 0.54 × 10−3 mm2/s. The sensitivity, specificity, and Youden Index for diagnosing seminoma were 99%, 31%, and 30%, respectively. Conclusion: High b-value DWI has potential utility for differentiating mumps orchitis from seminoma in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Synucleinopathies and tauopathies are characterized by progressive deposition of α‐synuclein (α‐syn) and tau proteins, respectively. These diseases have been linked to proteins mutations or excess α‐syn gene, indicating prominent roles of these proteins in their etiology and pathogenesis. Consequently, being able to non‐invasively image these aggregates would allow early and accurate diagnosis to facilitate clinical trials on drugs targeting these lesions and eventually for prophylactic therapies. Recently, several dye‐based imaging probes with selectivity for tau aggregates have been developed but suitable imaging biomarkers for synucleinopathies are still unavailable. However, these β‐sheet binders bind to different amyloids and thereby lack specificity. Compared to β‐sheet dyes, single domain antibodies (sdAbs), found in camelids and a few other species, are highly specific and their small size allows better brain entry and distribution than whole antibodies. Method: To develop anti‐α‐syn or anti‐tau sdAbs, we immunized llamas with α‐syn and tau preparations, respectively. Phage display libraries were generated from peripheral blood mononuclear cells and screened for binding to α‐syn or tau proteins using various assays, resulting in prototype sdAbs deemed promising for in vivo imaging. Subsequently, these anti‐α‐syn or anti‐tau sdAbs were labeled with a near‐infrared tag and injected intravenously in synucleinopathy, tauopathy or control mice, followed by imaging in an In Vivo Imaging System (IVIS). Subsequently, brains were extracted for tissue analysis. Result: Intravenous injection of labeled anti‐α‐syn or anti‐tau sdAbs resulted in strong in vivo brain signal detected through the intact head in synucleinopathy and tauopathy mice, respectively, but not in control mice. Notably, anti‐α‐syn sdAbs did not give signal in tauopathy mice and vice versa. The in vivo brain signal correlated strongly with insoluble, soluble, and phospho‐antigen within the brain. Postmortem analysis revealed extensive co‐localization of the sdAb imaging probe with α‐syn or tau aggregates within neurons in the endosomal‐lysosomal system, indicating their interaction in these degradation pathways. Conclusion: These anti‐α‐syn or anti‐tau sdAb probes allow non‐invasive and specific in vivo imaging of α‐synuclein vs tau pathology in mice, with brain signals correlating strongly with lesion burden. These small antibody derivatives have great potential for in vivo diagnosis of these diseases. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is the leading cause of severe diarrhea in children and the most common cause of diarrhea in travelers. However, most ETEC infections in Shenzhen, China were from indigenous adults. In this study, we characterized 106 ETEC isolates from indigenous outpatients with diarrhea (77% were adults aged >20 years) in Shenzhen between 2015 and 2020 by whole-genome sequencing and antimicrobial susceptibility testing. Shenzhen ETEC isolates showed a remarkable high diversity, which belonged to four E. coli phylogroups (A: 71%, B1: 13%, E: 10%, and D: 6%) and 15 ETEC lineages, with L11 (25%, O159:H34/O159:H43, ST218/ST3153), novel L2/4 (21%, O6:H16, ST48), and L4 (15%, O25:H16, ST1491) being major lineages. Heat-stable toxin (ST) was most prevalent (76%, STh: 60% STp: 16%), followed by heat-labile toxin (LT, 17%) and ST + LT (7%). One or multiple colonization factors (CFs) were identified in 68 (64%) isolates, with the common CFs being CS21 (48%) and CS6 (34%). Antimicrobial resistance mutation/gene profiles of genomes were concordant with the phenotype testing results of 52 representative isolates, which revealed high resistance rate to nalidixic acid (71%), ampicillin (69%), and ampicillin/sulbactam (46%), and demonstrated that the novel L2/4 was a multidrug-resistant lineage. This study provides novel insight into the genomic epidemiology and antimicrobial susceptibility profile of ETEC infections in indigenous adults for the first time, which further improves our understanding on ETEC epidemiology and has implications for the development of vaccine and future surveillance and prevention of ETEC infections. [ABSTRACT FROM AUTHOR]

The serotyping of Vibrio parahaemolyticus , which is crucial to the surveillance and detection of outbreaks of vibriosis infection, has been widely used in many countries. In this study, we developed a molecular assay, named multiplex ligation reaction based on probe melting curve analysis (MLMA), for simultaneous identification of V. parahaemolyticus 57 K-serogroups. Based on the previous genomes of 418 strains including 39 K-serogroups and the 18 K-serogroups sequences from public databases, we obtained 57 K-serogroups specific gene sequences for designing primers and probes. The developed MLMA assay for identifying the V. parahaemolyticus 57 K-serogroups showed high reproducibility, with the intra- and inter-assay standard deviations and coefficients of variation of no more than 1°C and 1%, respectively. The limit of detection for all gene targets ranged from 0.1 to 1.0 ng/µl. We validated the MLMA assay with a double-blind test identifying 595 V. parahaemolyticus isolates using conventional serotyping methods for comparison. The results showed the kappa value between the MLMA assay and the traditional serological method was 0.936 and that there was a 96.97% consistency rate with conventional serotyping methods for all detected isolates. Additionally, five rare K-serogroups were identified using the MLMA assay, as well as 18 strains that could not be identified using the traditional serotyping method. Thus, the MLMA assay provides a rapid, robust, and promising tool for the molecular serotyping of V. parahaemolyticus K-serogroups and has the potential application to the detection of outbreaks and surveillance of V. parahaemolyticus infection. [ABSTRACT FROM AUTHOR]

The dynamic nature of Vibrio parahaemolyticus epidemiology has presented a unique challenge for disease intervention strategies. Despite the continued rise of disease incidence and outbreaks of vibriosis, as well as the global emergence of pandemic clones and serovariants with enhanced virulence, there is a paucity of molecular methods for the serotyping of V. parahaemolyticus strains to improve disease surveillance and outbreak investigations. We describe the development of a multiplex ligation reaction based on probe melting curve analysis (MLMA) for the simultaneous identification of 11 clinically most common V. parahaemolyticus serotypes spanning a 10-year period. Through extensive sequence analyses using 418 genomes, specific primers and probes were designed for a total of 22 antigen gene targets for the O- and K- serogroups. Additionally, the toxR gene was incorporated into the assay for the confirmation of V. parahaemolyticus. All gene targets were detected by the assay and gave expected Tm values, without any cross reactions between the 11 clinically common serotypes or with 38 other serotypes. The limit of identification for all gene targets ranged from 0.1 to 1 ng/μL. The intra- and inter-assay standard deviations and the coefficients of variation were no more than 1°C and <1% respectively, indicating a highly reproducible assay. A multicenter double-blind clinical study was conducted using the traditional V. parahaemolyticus identification workflow and the MLMA assay workflow in parallel. From consecutive diarrheal stool specimens (n = 6118) collected over a year at 10 sentinel hospitals, a total of 153 V. parahaemolyticus isolates (2.5%) were identified by both workflows. A total agreement (kappa = 1.0) between the serotypes identified by the MLMA assay and conventional serological method was demonstrated. This is the first molecular assay to simultaneously identify multiple clinically important V. parahaemolyticus serotypes, which satisfies the acute need for a practical, rapid and robust identification of V. parahaemolyticus serotypes to facilitate the timely detection of vibriosis outbreaks and surveillance. [ABSTRACT FROM AUTHOR]

• Isolates with chromosomally located bla CTX-M-14b form into a clade in China. • The qnrS1 gene transferred from a plasmid to the chromosome. • Being located on the chromosome causes stable existence of resistance genes. Highly fluoroquinolone-resistant Salmonella enterica serotype Kentucky has become widespread in recent years, largely associated with the spread of sequence type 198 (ST198), which often leads to multidrug resistance. Research on the genomic epidemiology of Salmonella Kentucky in China is currently uncommon. In this study, we analysed the genomic epidemiology and antimicrobial resistance characteristics of Salmonella Kentucky ST198 collected from foodborne disease surveillance in Shenzhen, China, during 2010–2021, using whole-genome sequencing and antibiotic susceptibility testing. In addition, 158 global Salmonella Kentucky ST198 genomes were included for comparison. Among 8559 Salmonella isolates, 43 Salmonella Kentucky ST198 isolates were detected during 2010–2021. The global Salmonella Kentucky ST198 evolutionary tree was divided into five clades, with Shenzhen isolates distributed in clades 198.1, 198.2-1 and 198.2-2, mainly clustered with Chinese strains. Strains in clade 198.2 dominated in Shenzhen and all of them showed multidrug resistance. Nine strains showed high resistance to ceftriaxone, which was associated with bla CTX-M-14b in clade 198.2-1, which was demonstrated to be located on the chromosome. Fifteen strains showed high resistance to ciprofloxacin, which was associated with carriage of qnrS1 in clade 198.2-2. qnrS1 was first located on an IncHI2 plasmid and then transferred into the chromosome. Here we report the genomic and antimicrobial resistance characterisation of Salmonella Kentucky ST198 in Shenzhen. Of particular concern, we identified for the first time a clade 198.2-1 isolate carrying bla CTX-M-14b as well as chromosomally located qnrS1 in clade 198.2-2 of Salmonella Kentucky ST198 in China, highlighting the necessity of surveillance of clade 198.2. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown that the extent of pathological tau protein in the brain correlates strongly with the severity of Alzheimer's dementia at the time of death, and similar association with functional phenotypes have been seen in other tauopathies. In recent years, several dye‐based imaging probes with selectivity for tau aggregates have been developed. However, all are β‐sheet binders with varying affinity for different amyloids, and thereby lack specificity for tau lesions. In contrast, single domain antibodies (sdAbs) are specific for their target and because of their small size have much greater access into the brain than standard whole antibodies. Method: To examine sdAbs' suitability as non‐invasive in vivo imaging probes for tauopathies, we immunized a llama with a full‐length recombinant tau protein followed by boosters with human brain‐derived pathological tau proteins. Phage display libraries were generated from its peripheral blood mononuclear cells and screened for binding to tau proteins using various assays, resulting in a prototype sdAb deemed promising for in vivo imaging. Subsequently, this anti‐tau sdAb was labeled with a near‐infrared tag (680 nm), and injected intravenously in tauopathy and control mice, followed by imaging using an In Vivo Imaging System (IVIS). After the imaging, brains were extracted for tissue analysis. Result: Intravenous injection of labeled sdAb resulted in a strong in vivo brain signal detected through the intact head in two different models of transgenic tauopathy mice, but not in wild‐type or transgenic α‐synucleinopathy mice. Importantly, the in vivo brain signal correlated strongly with insoluble (r = 0.9839, p < 0.0001) and soluble (human tau (CP27) and phospho‐tau (PHF1): r = 0.9603 and 0.9459, p < 0.0001) tau protein within the brain. Furthermore, postmortem analysis revealed extensive co‐localization of the sdAb imaging probe with tau aggregates within neurons in the endosomal‐lysosomal system, indicating their interaction in these degradation pathways. Conclusion: Overall, this specific sdAb imaging ligand has great potential as an in vivo diagnostic marker for Alzheimer's disease and related tauopathies, and sdAb‐based imaging may be applicable to a variety of protein conformational disorders. [ABSTRACT FROM AUTHOR]

Proteus mirabilis is a common urinary tract pathogen, and may induce various inflammation symptoms. Its notorious ability to resist multiple antibiotics and to form urinary tract stones makes its treatment a long and painful process, which is further challenged by the frequent horizontal gene transferring events in P. mirabilis genomes. Three strains of P. mirabilis C02011/C04010/C04013 were isolated from a local outbreak of a food poisoning event in Shenzhen, China. Our hypothesis is that new genes may have been acquired horizontally to exert the digestion tract infection and toxicity. The functional characterization of these three genomes shows that each of them independently acquired dozens of virulent genes horizontally from the other microbial genomes. The representative strain C02011 induces the symptoms of both vomit and diarrhea, and has recently acquired a complete type IV secretion system and digestion tract toxic genes from the other bacteria. [ABSTRACT FROM AUTHOR]

A precisely positioned sulfilimine chiral center in the tether of a stabilized peptide would determine the peptide's secondary structure. Peptide sulfilimines could be prepared by a facile chloramine T oxidation and the two resulting peptide diastereomers showed significant differences in their secondary structures, which were supported by circular dichroism spectroscopy and NMR. [ABSTRACT FROM AUTHOR]

[Display omitted] YEATS domains, which are newly identified epigenetic readers of histone lysine acetylation and crotonylation, have emerged as promising anti-cancer drug targets. We recently developed AF9 YEATS domain-selective cyclopeptide inhibitors. However, the cumbersome and time-consuming synthesis of the cyclopeptides limited further structural derivatisation and applications. Here, we reported a concise method for the solid‐phase synthesis of the cyclopeptides, which substantially reduced the amount of time required for the preparation of the cyclopeptides and led to a higher overall yield. Moreover, this new synthetic route also allowed further derivatisation of the cyclopeptides with various functional modules, including fluorescent dye and cell‐penetrating peptide. We demonstrated that the conjugation of the cyclopeptide with cell-penetrating peptide TAT led to a significantly increased cellular uptake. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging signal contrast can be quantified by apparent diffusion coefficient (ADC) maps, which reflect the diffusion properties of the examined tissue and are helpful for identifying pathology. To determine ADC values of cryptorchid testes in post-pubertal patients and assess performance for characterizing cryptorchid testes. The medical records from 35 patients with unilateral scrotal vacuity were retrospectively reviewed. Data were analyzed in three groups: Group A, normal testes (i.e. the contralateral testes of the patients with cryptorchidism or MTC); Group B, cryptorchid testes; and Group C, malignant transformation of cryptorchidism (MTC) (seminoma). DWI used b-values of 0 and 800 s/mm2. Mean ADC values were compared using the independent samples t-test. The ability of ADC values was assessed using receiver operating characteristic curve analysis. The sensitivity, specificity, and accuracy were calculated. Mean ADC values for normal testes, cryptorchid testes, and MTC were 1.18 ± 0.18×10−3 mm2/s, 1.82 ± 0.40×10−3 mm2/s, and 0.80 ± 0.06×10−3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testes and cryptorchid testes or MTC (p < 0.001). The cut-off ADC value for differentiating normal testes from cryptorchid testes was 1.47 × 10−3 mm2/s. The sensitivity, specificity, and accuracy were 88%, 91%, and 90%, respectively. The cut-off ADC value for differentiating normal testes from MTC was 1.22 × 10−3 mm2/s. The sensitivity, specificity, and accuracy were 100%, 31%, and 43%, respectively. ADC values of cryptorchid testes may be used to inform clinical decision-making and also monitor testicular function in patients who retain undescended testicles or post-operatively. Mean ADC values of cryptorchidism and MTC (seminoma) were used to reflect their pathological features. [ABSTRACT FROM AUTHOR]

We report a new core-shell structure of peptide-Co 9 S 8 nanobricks for supercapacitor electrode. The nanostructured peptide is intrinsically flexible and biocompatible, which is highly suited for wearable supercapacitor electrodes. However, the application of the nanostructured peptide is often limited by its generally low power density and energy density, and its long-term stability is also a concern. Herein, the core-shell structure of peptide-Co 9 S 8 nanobricks is synthesized by conformally coating a thin shell layer of Co 9 S 8 via atomic layer deposition (ALD) onto self-assembled peptide nanobricks. The shell layer can not only protect the peptide material from being attacked by the electrolyte but also contribute extra capacitance to the supercapacitor. The supercapacitors made of the peptide-Co 9 S 8 nanobricks exhibit a high capacitance of 1.3 F/cm2 at 0.7 mA/cm2 and a much improved cycling stability of 96% capacitance retention after 5000 charge-discharge cycling. High-performance flexible solid-state asymmetric supercapacitor (SC) can be also made from the core-shell peptide-Co 9 S 8 nanobricks with activated carbon. The flexible asymmetric supercapacitor can also be coupled with a triboelectric nanogenerator (TENG) to afford a flexible self-powered TENG/SC system. The TENG/SC system with 2.7-h continuously charging by TENG can power a red LED for 21 min, which demonstrates its excellent performance of self-charging and energy-supplying, and therefore it is of great promise for future wearable electronics applications. Image 1 • A core-shell structure of peptide-Co 9 S 8 nanobricks electrode is synthesized and exhibits high supercapacitor performance. • The ALD Co 9 S 8 can protect the peptide material from being attacked by the electrolyte and also contribute extra capacitance. • A self-powered TENG/supercapacitor system is assembled by using peptide-Co 9 S 8 nanobricks as supercapacitor electrode. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is the most common cause of dementia in older individuals. AD is characterized pathologically by amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain, with associated loss of synapses and neurons, which eventually results in dementia. Many of the early attempts to develop treatments for AD focused on Aβ, but a lack of efficacy of these treatments in terms of slowing disease progression led to a change of strategy towards targeting of tau pathology. Given that tau shows a stronger correlation with symptom severity than does Aβ, targeting of tau is more likely to be efficacious once cognitive decline begins. Anti-tau therapies initially focused on post-translational modifications, inhibition of tau aggregation and stabilization of microtubules. However, trials of many potential drugs were discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting agents in clinical trials are immunotherapies. In this Review, we provide an update on the results from the initial immunotherapy trials and an overview of new therapeutic candidates that are in clinical development, as well as considering future directions for tau-targeting therapies. The limited success of amyloid-β-targeting therapies for Alzheimer disease has led to a shift in focus towards the tau protein. This Review provides an update on the initial trials of tau-targeting therapies, focusing particularly on immunotherapies, and considers future directions for these therapies. Key points: The limited success of amyloid-β-targeting therapies for Alzheimer disease (AD) has led to a shift in focus towards the tau protein — the main component of the neurofibrillary tangles that comprise the other major pathological hallmark of AD. Therapies targeting the expression, post-translational modifications, aggregation and clearance of tau have advanced to testing in humans. These therapies have been largely safe and well tolerated. The clinical efficacy of tau-targeting therapies has yet to be established and some trials have failed; however, multiple trials are ongoing and new candidates continue to enter trials. Antisense oligonucleotides have shown promising results in testing in humans for reducing tau expression, and larger studies will determine whether these findings translate into clinical benefits. Most of the tau-targeting therapies in ongoing trials are immunotherapies, which can target tau intracellularly and/or extracellularly, although extracellular targeting alone is less likely to be effective. The choice of epitope, the antibody subclass and its charge, the patient population and the mechanism of action must all be carefully considered when selecting antibodies and vaccines for clinical trials. Ideally, antibodies should be thoroughly retested after humanization, as this process might alter their properties. [ABSTRACT FROM AUTHOR]

Cerebral ischemia-reperfusion injury induces a secondary immune inflammatory reaction that exacerbates brain injury and clinical prognosis. Dendritic cells (DCs) and microglia are both important regulators of neuroinflammation. Studies have confirmed that a large number of cells express the DC surface marker CD11c in the ischemic area, and some of these cells also express microglial markers. However, the specific mechanism of transformation between microglia and DCs and their roles in the process of cerebral ischemia-reperfusion injury are still not clear. In this study, we established a mouse model and flow cytometry was used to detect the expression of mature DC surface molecules in activated microglia. IFN-γ knockout mice were used to determine the regulatory effect of IFN-γ on microglial transformation. We found that CD11c+ cells were derived from microglia after ischemia-reperfusion injury, and this group of cells highly expressed MHC-II molecules and other costimulatory molecules, such as CD80 and CD86, which were regulated by IFN-γ and its downstream signaling molecules ERK/c-myc. In summary, our results showed in cerebral ischemia-reperfusion injury, IFN-γ regulates the transformation of microglia to DC-like cells. Microglial-derived DC-like cells possess the ability to present antigens and activate naïve T cells which is regulated by the ERK/c-myc signaling pathway. • The present study firstly verified the regulation function of IFN-γ on microglia after cerebral ischemia/reperfusion, and this regulation is via ERK/c-myc signaling pathway. Microgliacould acquire antigen presentation functions during this process and thus involved in the neuro inflammation reactions. [ABSTRACT FROM AUTHOR]

• Long time high-salt diet exacerbated the following inflammation after stroke. • Sodium chloride rich in diet directly increased the pro-inflammatory M1 polarization of microglia during cerebra ischemia. • High salt diet upregulated the AR protein expressed on M1 microglia via p38/MAPK signal pathway. A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury. In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke. [ABSTRACT FROM AUTHOR]