Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review.

Inonotus obliquus, also known as Chaga, is a medicinal mushroom that has been used for therapeutic purposes since the sixteenth century. Collections of folk medicine record the application of Chaga for the treatment of diseases such as gastrointestinal cancer, diabetes, bacterial infection, and liver diseases. Modern research provides scientific evidence of the therapeutic properties of I. obliquus extracts, including anti-inflammatory, antioxidant, anticancer, anti-diabetic, anti-obesity, hepatoprotective, renoprotective, anti-fatigue, antibacterial, and antiviral activities. Various bioactive compounds, including polysaccharides, triterpenoids, polyphenols, and lignin metabolites have been found to be responsible for the health-benefiting properties of I. obliquus. Furthermore, some studies have elucidated the underlying mechanisms of the mushroom's medicinal effects, revealing the compounds' interactions with enzymes or proteins of important pathways. Thus, this review aims to explore available information on the therapeutic potentials of Inonotus obliquus for the development of an effective naturally sourced treatment option.

Glycerol Extraction of Bioactive Compounds from Thanaka (Hesperethusa crenulata) Bark through LCMS Profiling and Their Antioxidant Properties.

Organic solvents are hazardous to human and environmental health. The emergence of interest in finding greener solvents to replace organic solvents has sparked a series of studies in the use of glycerol for extracting bioactive compounds from natural products. In this study, we will first identify the bioactive compounds of glycerol- and nonglycerol-based Thanaka (Hesperethusa crenulata) bark extracts using liquid chromatography-mass spectrometry profiles; then, we will determine their antioxidant capacity, free radical scavenging activity, and total phenolic and flavonoid contents. Thanaka bark powder was extracted using solvents, namely, ethanol (TKE), water (TKW), glycerol (TKG), glycerol/water (1:1, v/v) (TKGW), and glycerol/ethanol (1:1, v/v) (TKGE). Among the five extracts, the extract of TKG has the highest number of bioactive compounds, as well as the highest total flavonoid content. TKGE possessed the highest total phenolic content and highest antioxidant activity shown in azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric-reducing antioxidant power assays among the five extracts. Overall, glycerol has better efficiency in extracting bioactive compounds from Thanaka bark as compared to ethanol and water. Hence, from the phytochemical content and antioxidant properties of Thanaka extracts, we conclude that glycerol is a good green solvent alternative to replace organic solvents.

The proteomic landscape of fall armyworm oral secretion reveals its role in plant adaptation.

BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda (J.E. Smith)) is a polyphagous agricultural pest with rapidly evolving adaptations to host plants. We found the oral secretion (OS) of FAW from different plants influences plant defense response differentially, suggesting its role in adapting to host plants. However, the protein expression profile of FAW OS respond to different plants is largely unknown. RESULTS: Here, from the mass spectrometry assay, we identified a total of 256 proteins in the OS of FAW fed on cotton (Gossypium hirsutum L.), tobacco (Nicotiana benthamiana Domin), maize (Zea mays L.) and artificial diet. The FAW OS primarily comprise of 60 proteases, 32 esterases and 92 non-enzymatic proteins. It displays high plasticity across different diets. We found that more than half of the esterases are lipases which have been reported as insect elicitors to enhance plant defense response. The lipase accumulation in cotton-fed larvae was the highest, followed by maize-fed larvae. In the presence of lipase inhibitors, the enhanced induction on defense genes in wounded leaves by OS was attenuated. However, the putative effectors were most highly accumulated in the OS from FAW larvae fed on maize compared to those fed on other diets. We identified that one of them (VRLP4) reduces the OS-mediated induction on defense genes in wounded leaves. CONCLUSION: Together, our investigation presents the proteomic landscape of the OS of FAW influenced by different diets and reveals diet-mediated plasticity of OS is involved in FAW adaptation to host plants. © 2024 Society of Chemical Industry.

Socioeconomic inequalities in healthcare system efficiency in Japan during COVID-19 pandemic: an analysis of the moderating role of vaccination.

Background: In the context of the COVID-19 pandemic, limited research has focused on socioeconomic disparities in Local Healthcare System Efficiency (LHSE) among Japanese prefectures. This study seeks to investigate the moderating impact of vaccination on the relationship between LHSE and socioeconomic characteristics and endowments. Methods: To explore these relationships, we first utilized the Data Envelopment Analysis with Slack-Based Measure to measure the LHSE, based on data from Japanese prefectures during waves 2 to 5 of the pandemic. Then estimating the impact of socioeconomic variables on LHSE. Finally, we assessed the changes in the way socioeconomic variables affect LHSE before and after vaccine deployment using the Seemingly Unrelated Estimation t-test methodology. Results: The research findings suggest an overall reduction in LHSE disparities across various regions due to the utilization of vaccines. Particularly in areas with relatively nsufficient bed resources, a significant improvement in LHSE was observed in most regions. However, there was no evidence supporting the role of vaccine deployment in mitigating socioeconomic inequalities in LHSE. Conversely, the utilization of vaccines showed a positive correlation between the improvement in LHSE and the proportion of older adult population in regions with sufficient bed resources. In regions facing bed shortages, the enhancement of LHSE became more reliant on reducing the occupancy rate of secured beds for severe cases after the introduction of vaccination. Discussion: In regions facing bed shortages, the enhancement of LHSE became more reliant on reducing the occupancy rate of secured beds for severe cases. This underscores the importance for policymakers and implementers to prioritize the treatment of severe cases and ensure an effective supply of medical resources, particularly secured beds for severe cases, in their efforts to improve LHSE, in the post-COVID-19 era with rising vaccine coverage.

Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Effects of stress on sleep quality: multiple mediating effects of rumination and social anxiety.

BACKGROUND: In contemporary society, with the accelerated pace of work and life, more and more people feel different degrees of stress. Long-term stress may not only lead to insomnia, but also to mental health problems (e.g., anxiety and depression), which has a significant impact on people's quality of life and mental health. OBJECTIVE: This study primarily investigates the mechanism through which stress affects sleep quality among college students. METHODS: We conducted research on 1653 Chinese college students using four scales with high reliability and validity: stress, the Pittsburgh Sleep Quality Index, social anxiety, and rumination. RESULTS: The study found: (1) Stress can significantly and positively predict sleep quality and rumination; (2) Rumination can positively predict social anxiety; (3) Social anxiety can positively predict sleep quality; (4) Stress can affect sleep quality through social anxiety and rumination separately, and stress can also affect sleep quality through the chained mediation of rumination and social anxiety. CONCLUSION: This study reveals the relationship and mechanisms between stress and sleep quality. It not only deepens the research on the impact of stress on sleep quality but also provides theoretical support and new methods for mental health professionals to help clients improve their sleep quality. In practice, in addition to using some common psychological intervention methods to help individuals reduce stress, we should pay more attention to how to help clients reduce rumination and social anxiety, This is significant in improving the quality of an individual's sleep.

FUS reads histone H3K36me3 to regulate alternative polyadenylation.

Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3 recognition of FUS was mediated by the proline residues in the ZNF domain. After these proline residues were mutated or H3K36me3 was abolished, FUS dissociated from chromatin and bound more to RNA, resulting in an increase in polyadenylation sites far from stop codons genome-wide. A proline mutation corresponding to a mutation in amyotrophic lateral sclerosis contributed to the hyperactivation of mitochondria and hyperdifferentiation in mouse embryonic stem cells. These findings reveal that FUS is an H3K36me3 reader protein that links chromatin-mediated alternative polyadenylation to human disease.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

An isochronous stress ratio logarithmic strain curve based clay creep model considering the effects of hardening and damage.

Creep is one of the typical mechanical properties of clay, and studying the creep mechanical properties of clay is of great significance to construction projects in clay sites. This study conducted creep tests on Chengdu clay and found that the soil mass underwent elastic deformation, decay creep deformation, steady-state creep deformation, and accelerated creep deformation. The isochronous stress ratio-logarithmic strain curves and their mathematical models were proposed to thoroughly analyze clay creep mechanical properties. Creep automatic feature points, such as linear elastic extreme point, initial yield point, long-term strength point, and plastic point, were identified on the curve. Considering the hardening and damage effects during creep loading, linear elastic and viscoelastic elements considering the time-dependent damage, a viscoplastic element considering the load hardening effect, and viscoplastic and plastic elements considering the load damage effect were established based on the element model and the Riemann-Liouville fractional derivative. Based on the mechanical properties of the whole clay creep process, the creep mechanical feature points, and the established element model, a clay creep model was proposed considering the hardening and damage effects. The rationality and regularity of the creep model were verified using the creep test data. This research accurately revealed the creep mechanical properties of clay and facilitated soil deformation prediction, thus providing technical guidance and references for construction projects in clay sites.

Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

A novel method for evaluating load restraint assemblies to ensure the safety of railway freight transportation.

The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

Microarray analysis identifies lncFirre as a potential regulator of obesity-related acute lung injury.

AIMS: The inflammatory response in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is heightened in obesity. The aim of this study was to investigate whether lncRNAs are involved in the effects of obesity on acute lung injury and to find possible effector lncRNAs. MAIN METHODS: Microarray analysis was used to assess the transcriptional profiles of lncRNAs and mRNAs in lung tissues from normal (CON), high-fat diet induced obese (DIO), and obese ALI mice (DIO-ALI). GO and KEGG analyses were employed to explore the biological functions of differentially expressed genes. A lncRNA-mRNA co-expression network was constructed to identify specific lncRNA. Lung tissues and peripheral blood samples from patients with obesity and healthy lean donors were utilized to confirm the expression characteristics of lncFirre through qRT-PCR. lncFirre was knocked down in MH-S macrophages to explore its function. ELISA and Griess reagent kit were used to detect PGE2 and NO. Flow cytometry was used to detect macrophages polarization. KEY FINDINGS: There were 475 lncRNAs and 404 mRNAs differentially expressed between DIO and CON, while 1348 lncRNAs and 1349 mRNAs between DIO-ALI and DIO. Obesity increased lncFirre expression in both mice and patients, and PA elevated lncFirre in MH-S. PA exacerbated the inflammation and proinflammatory polarization of MH-S induced by LPS. LncFirre knockdown inhibited the secretion of PGE2 and NO, M1 differentiation while promoted the M2 differentiation in PA and LPS co-challenged MH-S. SIGNIFICANCE: Interfering with lncFirre effectively inhibit inflammation in MH-S, lncFirre can serve as a promising target for treating obesity-related ALI.

Heterogeneous electro-Fenton treatment of coking wastewater using Fe/AC/Ni cathode: optimization of electrode and reactor organic loading.

A self-developed iron-loaded activated carbon-based nickel foam electrode (Fe/AC/Ni cathode) was used to construct electro-Fenton reaction system to treat coking wastewater. To meet the gap between laboratory beaker experiments and field trials for practical applications, we proposed and validated a method for obtaining organic loads, the essential parameters used in the design of electrochemical systems for wastewater treatment. The three influencing factors most relevant to organic loading, the effective surface area of cathode, chemical oxygen demand (COD) concentration of influent, and treatment time, were selected and investigated for their effects on the COD removal rate of coking wastewater by single-factor experiments and further optimized by response surface method. The appropriate electrode area load (La) and reactor volume load (Lv) were calculated by their corresponding intrinsic relationships with the three factors. The optimum application conditions were effective surface area of cathode 28.5 cm2, COD concentration of influent 1.76 kg·m-3, and treatment time 160.43 min. Under these conditions, the maximum COD removal rate was 98.51%. The La and Lv were 8.905 mgCOD·cm-2·h-1 and 0.634 kgCOD·m-3·h-1, respectively. The characterization experiment results showed that the Fe/AC/Ni cathode had a significant effect on the treatment of refractory organic contaminants in coking wastewater.

Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children: analysis of 571 patients.

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).

Efficient photocatalytic NO removal with inhibited NO2 formation and catalyst loss over sponge-supported and functionalized g-C3N4.

Though photocatalytic purification of NO has been widely studied, how to avoid secondary pollution during gas-solid reaction is still a challenge, especially in inhibiting the formation of toxic intermediates (NO2) and avoiding the blow away of powdery photocatalyst. Herein, we proposed a one-step solvothermal method to prepare melamine sponge (MS) supported and functionalized g-C3N4 (CN), which simultaneously realizes the inhibition of NO2 formation and catalyst loss. Sodium hydroxide, which plays a dual role, has been introduced during the preparation of supported photocatalyst. Specifically, sodium atom, as the modifier of performance, could facilitate the randomly distributed charge of pristine CN to be converged, which accelerates the adsorption/activation of reactants for efficient and deep NO oxidation. Hydroxyl group, as the binder between CN and MS, induces the interaction by forming hydrogen bonds, which contributes to the firm immobilization of powdery photocatalyst. The supported sample exhibits outstanding NO removal rate (58.90%) and extremely low NO2 generation rate (1.41%), and the mass loss rate of photocatalyst before and after reaction is less than 1%. The promotion mechanism of performance also has been elaborated. This work takes environmental risks as a prerequisite to propose a feasible strategy for perfecting the practical application of photocatalytic technology.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

Investigating the spontaneous brain activities of patients with subjective cognitive decline and mild cognitive impairment: an amplitude of low-frequency fluctuation functional magnetic resonance imaging study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are neurodegenerative processing stages of Alzheimer's disease (AD). Cognitive decline is thought to manifest in intrinsic brain activity changes, but research results yielded conflicting and few studies have explored the roles of brain regions in cognitive decline, and sensitivity of the cognitive field to changes in the altered intrinsic brain activity. Methods: In this cross-sectional study, 158 elderly participants were recruited from the memory clinic of the First Affiliated Hospital of Nanjing Medical University from July 2019 to May 2021, and grouped into SCD (n=73), MCI (n=46), and normal controls (NC) (n=39). The amplitude of low-frequency fluctuation (ALFF) was calculated and evaluated among the groups. Then canonical correlation analysis (CCA) was conducted to investigate the associations between imaging outcomes and cognitive behaviors. Results: Neuropsychological tests in different cognitive dimensions and ALFF values of the prefrontal, parietal, and temporal gyrus, were significantly different (P<0.05) among the three groups, with no appreciable decline in daily activity. The changes in intrinsic activities were closely related to the decline in cognitive function (R=0.73, P=0.002). ALFF values in the left middle occipital gyrus, right middle frontal gyrus, left superior frontal gyrus, left angular gyrus, and superior temporal gyrus played significant roles in the analysis, while the Montreal Cognitive Assessment (MoCA) and Auditory-Verbal Learning Test scores were found to be more sensitive to changes in ALFF values. Conclusions: Spontaneous brain activity is a stable imaging biomarker of cognitive impairment. ALFF changes of the prefrontal, occipital, left angular, and temporal gyrus were sensitive to identifying cognitive decline, and the scores of the Auditory-Verbal Learning Test and MoCA could predict the abnormal intrinsic activities.

Insights from insulin resistance pathways: Therapeutic approaches against Alzheimer associated diabetes mellitus.

Alzheimer Associated Diabetes Mellitus, commonly known as Type 3 Diabetes Mellitus (T3DM) is a distinct subtype of diabetes with a pronounced association with Alzheimer's disease (AD). Insulin resistance serves as a pivotal link between these two conditions, leading to diminished insulin sensitivity, hyperglycemia, and impaired glucose uptake. The brain, a vital organ in AD context, is also significantly impacted by insulin resistance, resulting in energy deficits and neuronal damage, which are hallmark features of the neurodegenerative disorder. To pave the way for potential therapeutic interventions targeting the insulin resistance pathway, it is crucial to comprehend the intricate pathophysiology of T3DM and identify the overlapped features between diabetes and AD. This comprehensive review article aims to explore various pathway such as AMPK, PPARγ, cAMP and P13K/Akt pathway as potential target for management of T3DM. Through the analysis of these complex mechanisms, our goal is to reveal their interdependencies and support the discovery of innovative therapeutic strategies. The review extensively discusses several promising pharmaceutical candidates that have demonstrated dual drug action mechanisms, addressing both peripheral and cerebral insulin resistance observed in T3DM. These candidates hold significant promise for restoring insulin function and mitigating the detrimental effects of insulin resistance on the brain. The exploration of these therapeutic options contributes to the development of innovative interventions that alleviate the burden of T3DM and enhance patient care.

Non-Mass Spectrometric Targeted Single-Cell Metabolomics.

Metabolic assays serve as pivotal tools in biomedical research, offering keen insights into cellular physiological and pathological states. While mass spectrometry (MS)-based metabolomics remains the gold standard for comprehensive, multiplexed analyses of cellular metabolites, innovative technologies are now emerging for the targeted, quantitative scrutiny of metabolites and metabolic pathways at the single-cell level. In this review, we elucidate an array of these advanced methodologies, spanning synthetic and surface chemistry techniques, imaging-based methods, and electrochemical approaches. We summarize the rationale, design principles, and practical applications for each method, and underscore the synergistic benefits of integrating single-cell metabolomics (scMet) with other single-cell omics technologies. Concluding, we identify prevailing challenges in the targeted scMet arena and offer a forward-looking commentary on future avenues and opportunities in this rapidly evolving field.