Phase-separated ParB enforces diverse DNA compaction modes and stabilizes the parS-centered partition complex.

The tripartite ParABS system mediates chromosome segregation in the majority of bacterial species. Typically, DNA-bound ParB proteins around the parS sites condense the chromosomal DNA into a higher-order multimeric nucleoprotein complex for the ParA-driven partition. Despite extensive studies, the molecular mechanism underlying the dynamic assembly of the partition complex remains unclear. Herein, we demonstrate that Bacillus subtilis ParB (Spo0J), through the multimerization of its N-terminal domain, forms phase-separated condensates along a single DNA molecule, leading to the concurrent organization of DNA into a compact structure. Specifically, in addition to the co-condensation of ParB dimers with DNA, the engagement of well-established ParB condensates with DNA allows for the compression of adjacent DNA and the looping of distant DNA. Notably, the presence of CTP promotes the formation of condensates by a low amount of ParB at parS sites, triggering two-step DNA condensation. Remarkably, parS-centered ParB-DNA co-condensate constitutes a robust nucleoprotein architecture capable of withstanding disruptive forces of tens of piconewton. Overall, our findings unveil diverse modes of DNA compaction enabled by phase-separated ParB and offer new insights into the dynamic assembly and maintenance of the bacterial partition complex.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

Systematic review of the mechanism and assessment of liver fibrosis in biliary atresia.

PURPOSE: This study systematically reviewed our team's research on the mechanism and assessment of liver fibrosis in BA, summarized our experience, and discussed the future development direction. METHODS: In this study, Pubmed and Wanfang databases were searched to collect the literature published by our team on the mechanisms of liver fibrosis in BA and the assessment of liver fibrosis in BA, and the above research results were systematically reviewed. RESULTS: A total of 58 articles were retrieved. Among the included articles, 25 articles related to the mechanism of liver fibrosis in BA, and five articles evaluated liver fibrosis in BA. This article introduces the key pathways and molecules of liver fibrosis in BA and proposes a new grading system for liver fibrosis in BA. CONCLUSIONS: The new BA liver fibrosis grading method is expected to assess children's conditions, guide treatment, and improve prognosis more accurately. In addition, we believe that the TGF-ß1 signaling pathway is the most important in the study of liver fibrosis in BA, and at the same time, the study of EMT occurrence in BA should also be deepened to resolve the controversy on this issue.

High-Sensitivity and Wide-Range Flexible Ionic Piezocapacitive Pressure Sensors with Porous Hemisphere Array Electrodes.

The development of high-performance flexible pressure sensors with porous hierarchical microstructures is limited by the complex and time-consuming preparation processes of porous hierarchical microstructures. In this study, a simple modified heat curing process was first proposed to achieve one-step preparation of porous hemispherical microstructures on a polydimethylsiloxane (PDMS) substrate. In this process, a laser-prepared template was used to form surface microstructures on PDMS film. Meanwhile, the thermal decomposition of glucose monohydrate additive during heat curing of PDMS led to the formation of porous structures within PDMS film. Further, based on the obtained PDMS/CNTs electrodes with porous hemisphere array and ionic polymer dielectric layers, high-performance ionic piezocapacitive sensors were realized. Under the synergistic effect of the low-stiffness porous hemisphere microstructure and the electric double layer of the ionic polymer film, the sensor based on an ionic polymer film with a 1:0.75 ratio of P(VDF-HFP):[EMIM][TFSI] not only achieves a sensitivity of up to 106.27 kPa-1 below 3 kPa, but also has a wide measurement range of over 400 kPa, which has obvious advantages in existing flexible piezocapacitive sensors. The rapid response time of 110 s and the good stability of 2300 cycles of the sensor further elucidate its practicality. The application of the sensor in pulse monitoring, speech recognition, and detection of multiple dynamic loads verifies its excellent sensing performance. In short, the proposed heat curing process can simultaneously form porous structures and surface microstructures on PDMS films, greatly simplifying the preparation process of porous hierarchical microstructures and providing a simple and feasible way to obtain high-performance flexible pressure sensors.

Chiral Jahn-Teller Distortion in Quasi-Planar Boron Clusters.

In this work, we have observed that some chiral boron clusters (B16-, B20-, B24-, and B28-) can simultaneously have helical molecular orbitals and helical spin densities; these seem to be the first compounds discovered to have this intriguing property. We show that chiral Jahn-Teller distortion of quasi-planar boron clusters drives the formation of the helical molecular spin densities in these clusters and show that elongation/enhancement in helical molecular orbitals can be achieved by simply adding more building blocks via a linker. Aromaticity of these boron clusters is discussed. Chiral boron clusters may find potential applications in spintronics, such as molecular magnets.

Hyperuricemia May Increase Risk of Achilles Tendon Rupture: A Case Control Study.

It has been demonstrated in a number of studies that high levels of uric acid can cause crystal deposition in the tendons of the lower extremities, which in turn can impair the Achilles tendon. This study aimed to interpret whether hyperuricemia is relevant with Achilles tendon rupture. Patients diagnosed with Achilles tendon rupture at the same institution between 2013 and 2022 were included in the case group. Healthy subjects who had physical examinations during the same period were included in the control group. Propensity score matching was used to match in a 1:1 ratio. Demographic and clinical characteristics of patients in both groups were compared. Five hundred and fourteen patients were included in the study (ATR=257; Control group=257). The proportion of individuals with hyperuricemia varied significantly between the 2 groups (Achilles tendon rupture group=43.6%; control group=27.6%; p<0.001). The Achilles tendon rupture and hyperuricemia were linked by conditional logistic regression (p<0.001; OR=2.036; 95CI%=1.400-2.961). Compared with healthy subjects, patients with hyperuricemia have a higher risk of Achilles tendon rupture. Further studies are required to verify the effects of hyperuricemia and monosodium urate crystals on Achilles tendon structure.

Diagnostic and prognostic value of the gut microbiota and its metabolite butyrate in children with biliary atresia.

PURPOSE: To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora. METHODS: A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography. RESULTS: Taxonomic analysis revealed significant differences in the composition of the intestinal microbiota between BA patients and controls, with a reduction in diversity and a higher abundance of Proteobacteria, Streptococcus and Lactobacillus in the BA group. Database and clinical data analyses concluded that Streptococcus/Bacteroides (AUC = 0.9035, 95% CI 0.8347-0.9722, P < 0.0001) or Streptococcus/Eggerthella (AUC = 0.8333, 95% CI 0.6340-1.000, P = 0.027) was the best microbiota to differentiate between BA and DC. Serum butyrate levels were low in the BA and DC groups and differed from the HC group (P = 0.01, P = 0.04). Butyrate levels in BA were negatively correlated with jaundice clearance and cholangitis, but not statistically significant. CONCLUSIONS: Our study reveals changes in the composition of the gut microbiota in BA, especially the butyrate-producing microbiota, and suggests the potential for using gut microbiota as a noninvasive diagnostic benefit for BA. Low levels of serum butyrate in BA may indicate a poor prognosis.

[Research advances in exosomes involved in the occurrence, development and clinical diagnosis and treatment of sepsis].

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The development of sepsis is accompanied by the secretion of exosomes by a variety of cells, including non-coding RNA, metabolic small molecules and proteins, which play an important role in immune inflammatory response, oxidative stress, and coagulation dysfunction. The rapid development of new detection technologies has promoted the application of exosomes in the early warning, severity stratification, treatment effect and prognosis evaluation of sepsis. This article reviews the new detection technology of exosomes, the involvement of exosomes in the pathological progress of sepsis, and the latest progress in the early diagnosis, disease assessment and treatment of sepsis, in order to provide new ideas for the diagnosis and treatment of sepsis.

Quantitative Study on the Influence of Bromide Ions toward the Reduction Kinetics for Size-Tunable Palladium Nanocubes.

During the preparation of nanocrystals, regulating the dosage of key additives in the reaction system and the reaction temperature commonly affects the sizes and morphologies of the products. Despite the fact that bromide ions play a pivotal role in the synthesis of palladium nanocubes (Pd NCs), there is still a lack of quantitative and in-depth research on how the ions affect the reduction kinetics of Pd precursors and further on products. In this work, Pd NCs with different sizes have been prepared under various reaction conditions coupled to a systematic mechanism study. Quantitative measurements demonstrate that the reduction processes could be considered quasi-first-order reactions, and the corresponding kinetic parameters have been obtained. Furthermore, a linear relationship is discovered between k and the average size (d) of Pd NCs. The investigation on the growth patterns of four chosen systems reveals that given reaction conditions lead to certain results with unique growth patterns.

Sequential respiratory support in septic patients undergoing continuous renal replacement therapy: A study based on MIMIC-III database.

Objective: Oxygen and hemodynamic management are important for providing a sufficient adequate oxygen-containing blood to the organs for septic patients. In present study, we aimed to explore the application of sequential respiratory support (SRS) and the association of SRS with the outcome of septic patients who needed continuous renal replacement therapy (CRRT). Methods: We extracted the medical information of septic patients who received CRRT within 24 h of intensive care unit (ICU) admission from the MIMIC-III v1.4. SRS was defined as receiving firstly oxygen therapy followed by mechanical ventilation (MV) within 24 h of admission to ICU. The propensity score matching (PSM) was performed to compare the differences in clinical characteristics and outcomes of patients with or without SRS. Finally, we developed logistic regression models to analyze the effects of SRS on hospital mortality. Results: A total of 181 patients entered in this study, and there were 80 patients undergoing MV including SRS group (n = 61) and non-SRS group (n = 19). In the multivariate logistic regression, the value of SRS was associated with the lower risk of hospital mortality adjusted by minimum systolic BP (SBP), maximum lactate, vasopressor use, and sequential organ failure assessment (SOFA) score or Logistic Organ Dysfunction System (LODS) scores within the first 24 h of ICU stay. After PSM adjusted by SBP, maximum lactate, vasopressor use, SOFA, and LODS, there were 31 patients in SRS group with a and 18 cases in non-SRS group, displaying a significantly lower hospital mortality in SRS group than that in patients without SRS (19.4 % vs. 83.3 %, P < 0.001). In addition, age, qSOFA, necessitating the administration of vasopressor, and duration of vasopressor were significantly correlated with the hospital mortality in septic patients undergoing CRRT and SRS. Conclusions: Receiving SRS within the first 24 h upon admission to the ICU was independently associated with the hospital mortality in patient with sepsis undergoing CRRT, and patients who were directly received MV had a high risk of death.

Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report.

BACKGROUND: Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY: A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION: This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

Hypoglycemic Response to Dorzagliatin in a Patient With GCK-MODY.

OBJECTIVE: Metformin, insulin, and insulin secretagogues do not alter HbA1c levels in glucokinase maturity-onset diabetes of the young (GCK-MODY). However, the efficacy of the new hypoglycemic drugs on GCK-MODY remains unclear. RESEARCH DESIGN AND METHODS: We describe a case of GCK-MODY with unchanged blood glucose under different therapies during an 8 years' follow-up. His HbA1c and biochemical indices under different hypoglycemic treatments were recorded. RESULTS: Oral glucose-lowering drugs, including thiazolidinediones, dipeptidyl peptidase 4 inhibitor, α-glucosidase inhibitor, and sodium-glucose cotransporter 2 inhibitor that had not been evaluated previously, did not improve the HbA1c level in this patient. However, the glucokinase activator dorzagliatin effectively and safely lowered his HbA1c level. CONCLUSIONS: Dorzagliatin was effective and safe in this patient with GCK-MODY, providing potential application prospects for precise treatment of GCK-MODY with dorzagliatin.

Multifunctional molecularly imprinted nanozymes with improved enrichment and specificity for organic and inorganic trace compounds.

Although nanozymes exhibit properties superior to those of natural enzymes and conventional engineered enzymes, the development of highly specific nanozymes remains a challenge. New yolk-shell Fe3O4 molecularly imprinted (MIP@void@Fe3O4) nanozymes with peroxidase-like activity were developed by modelling the substrate channels of natural enzymes through molecular imprinting techniques and interfacial affinity modifications in this study. To establish a platform technology for the adsorption and determination of inorganic and organic contaminants, lead ion (Pb2+) and diazinon (DIZ), respectively, were selected as imprinting templates, and a hollow mesoporous shell was synthesized. The as-prepared MIP@void@Fe3O4 nanozymes, characterized using TEM, HRTEM, SEM, FT-IR, TGA, VSM and XPS, not only affirmed the successful fabrication of a magnetic nanoparticle with a unique hollow core-shell structure but also facilitated an exploration of the interfacial bonding mechanisms between Fe3O4 and other shell layers. The enrichment of the MIP@void@Fe3O4 nanozymes due to imprinting was approximately 5 times higher than the local substrate concentration and contributed to the increased activity. Based on selective and competitive recognition experiments, the synthesized nanozymes could selectively recognize organic and inorganic targets with the lowest detection limits (LOD) of 6.6 × 10-9 ppm for Pb2+ and 5.13 × 10-11 M for DIZ. Therefore, the proposed biosensor is expected to be a potent tool for trace pollutant detection, which provides a rational design for more advanced and subtle methods to bridge the activity gap between natural enzymes and nanozymes.

Fragment-Based Deep Learning for Simultaneous Prediction of Polarizabilities and NMR Shieldings of Macromolecules and Their Aggregates.

Simultaneous prediction of the molecular response properties, such as polarizability and the NMR shielding constant, at a low computational cost is an unresolved issue. We propose to combine a linear-scaling generalized energy-based fragmentation (GEBF) method and deep learning (DL) with both molecular and atomic information-theoretic approach (ITA) quantities as effective descriptors. In GEBF, the total molecular polarizability can be assembled as a linear combination of the corresponding quantities calculated from a set of small embedded subsystems in GEBF. In the new GEBF-DL(ITA) protocol, one can predict subsystem polarizabilities based on the corresponding molecular wave function (thus electron density and ITA quantities) and DL model rather than calculate them from the computationally intensive coupled-perturbed Hartree-Fock or Kohn-Sham equations and finally obtain the total molecular polarizability via a linear combination equation. As a proof-of-concept application, we predict the molecular polarizabilities of large proteins and protein aggregates. GEBF-DL(ITA) is shown to be as accurate enough as GEBF, with mean absolute percentage error <1%. For the largest protein aggregate (>4000 atoms), GEBF-DL(ITA) gains a speedup ratio of 3 compared with GEBF. It is anticipated that when more advanced electronic structure methods are used, this advantage will be more appealing. Moreover, one can also predict the NMR chemical shieldings of proteins with reasonably good accuracy. Overall, the cost-efficient GEBF-DL(ITA) protocol should be a robust theoretical tool for simultaneously predicting polarizabilities and NMR shieldings of large systems.

Enhancing Cu-ligand interaction for efficient CO2 reduction towards multi-carbon products.

Electrochemical CO2 reduction (CO2R) to valuable products provides a promising strategy to enable CO2 utilization sustainably. Here, we report the strategy of using Cu-DAT (3,5-diamino-1,2,4-triazole) as a catalyst precursor for efficient CO2 reduction, demonstrating over 80% selectivity towards multicarbon products at 400 mA cm-2, with intrinsic activity over 19 times higher than that of Cu nanoparticles. The catalyst's active phase is determined to be metallic copper wrapped with the DAT ligand. We attribute this enhanced CO2R performance to the accelerated steps of *CO adsorption and C-C coupling induced by the closely cooperated DAT ligand.

Study on antimicrobial activity of sturgeon skin mucus polypeptides (Rational Design, Self-Assembly and Application).

Despite the favorable biocompatibility of natural antimicrobial peptides (AMPs), their scarcity limits their practical application. Through rational design, the activity of AMPs can be enhanced to expand their application. In this study, we selected a natural sturgeon epidermal mucus peptide, AP-16 (APATPAAPALLPLWLL), as the model molecule and studied its conformational regulation and antimicrobial activity through amino acid substitutions and N-terminal lipidation. The structural and morphological transitions of the peptide self-assemblies were investigated using circular dichroism and transmission electron microscopy. Following amino acid substitution, the conformation of AL-16 (AKATKAAKALLKLWLL) did not change. Following N-terminal alkylation, the C8-AL-16 and C12-AL-16 conformations changed from random coil to ß-sheet or α-helix, and the self-assembly changed from nanofibers to nanospheres. AL-16, C8-AL-16, and C8-AL-16 presented significant antimicrobial activity against Pseudomonas and Shewanella at low concentrations. N-terminal alkylation effectively extended the shelf life of Litopenaeus vannamei. These results support the application of natural AMPs.

Investigation of the structure, rheology and 3D printing characteristics of corn starch regulated by glycyrrhizic acid.

This study aimed to construct a novel corn starch-glycyrrhizic acid (CS-GA) ink and systematically investigate the effects of GA on the water distribution, microstructure, rheology and 3D printing properties of CS hydrogels. The results showed that the CS chains could form strong hydrogen bonds with GA molecules, inhibit the formation of short-range ordered structure of CS and reduce the content of B-type starch. The low-field nuclear magnetic results showed that the introduction of GA could increase bound water content in CS-GA hydrogels. With the increase of GA content, the CS-GA hydrogel changed from CS-dominated to a GA-dominated gel network system. Rheological results showed that all samples exhibited typical shear thinning behavior. High GA concentration was beneficial to increasing the self-supporting properties and thixotropic recovery of CS-GA hydrogels. Compared with the pure CS hydrogel, the 3D printing characteristics of CS-GA hydrogels were significantly enhanced due to the increased bound water content and the enhancement of rheological properties. At 40 % GA content, CS-GA hydrogel showed the highest printing accuracy of 96.4 % ± 0.30 %. The printed product could perfectly replicate the preset model. Therefore, this study provided a theoretical basis for regulating starch's rheology and 3D printing characteristics and developing novel food-grade 3D printing inks.

Effect of Heat Treatment Combined with TG Enzyme Cross-Linking on the Zein-Pea Protein Complex: Physicochemical and Gel Properties.

Plant proteins have the advantages of low cost and high yield, but they are still not comparable to animal proteins in processing due to factors such as gelation and solubility. How to enhance the processing performance of plant proteins by simple and green modification means has become a hot research topic nowadays. Based on the above problems, we studied the effect of gel induction on its properties. In this study, a pea protein-zein complex was prepared by the pH cycle method, and the effects of different induced gel methods on the gel properties of the complex protein were studied. The conclusions are as follows: All three gel induction methods can make the complex protein form a gel system, among which the gel strength of heat treatment and the TG enzyme-inducted group is the highest (372.84 g). Through the observation of the gel microstructure, the gel double network structure disappears and the structure becomes denser, which leads to a stronger water-binding state of the gel sample in the collaborative treatment group. In the simulated digestion experiment, heat treatment and enzyme-induced samples showed the best slow-release effect. This study provides a new method for the preparation of multi-vegetable protein gels and lays a theoretical foundation for their application in food processing.

Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders.

Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.