The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning.

We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) -related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single-Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC-related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

[Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder].

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods.

Benzodiazepines (BDZs) are used in clinics for anxiolysis, anticonvulsants, sedative hypnosis, and muscle relaxation. They have high consumptions worldwide because of their easy availability and potential addiction. They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault. The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging. Efficient pretreatment methods followed by accurate and sensitive detections are necessary. Herein, pretreatment methods for the extraction, enrichment, and preconcentration of BDZs as well as the strategies for their screening, identification, and quantitation developed in the past five years have been reviewed. Moreover, recent advances in various methods are summarized. Characteristics and advantages of each method are encompassed. Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer.

Background: Bladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes. Methods: We used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis. Results: The GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins. Conclusions: The GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel "Glutamine Metabolism-related Gene"-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer.

P-PBFT: An improved blockchain algorithm to support large-scale pharmaceutical traceability.

To solve the problems of high latency, high system overhead, and small supported scale in the current application of pharmaceutical traceability combined with blockchain technology, an algorithm called Pharmaceutical-Practical Byzantine Fault Tolerance (P-PBFT) based on PBFT, grouping, and credit voting is proposed. The algorithm combines the characteristics of a pharmaceutical supply chain, optimizes the consistency protocol in the original algorithm, divides large-scale network nodes into different consensus sets by response speed, and performs grouping consensus. The algorithm's credit model and voting mechanism dynamically updates user status according to the behavior of nodes in consensus, evaluates the reliability of users, and also serves as a basis for electing management nodes. Experimental results show that the improved P-PBFT consensus algorithm provides smaller latency and higher throughput for pharmaceutical traceability systems, supports larger-scale traceability, effectively alleviates the dramatic increase in communication among network nodes, and reduces the influence of malicious nodes.

Sweeteners in food samples: An update on pretreatment and analysis techniques since 2015.

Sweeteners play an irreplaceable role in daily life and have been found in multitudinous food products. However, excessive or unreasonable intake of sweeteners as food additives brings about untoward problems due to the accumulation in the human body. Therefore, a comprehensive review of different sweeteners' pretreatment and determination methods is urgently needed. In this review, we comprehensively reviewed the progress of different pretreatment and detection methods for sweeteners in various food, focusing on the latest development since 2015. Current state-of-the-art technologies, such as headspace single-drop microextraction, ultrasound-assisted emulsification microextraction, solid-phase microextraction, two-dimensional liquid chromatography, and high-resolution mass spectrometry, are thoroughly discussed. The advantages, disadvantages, critical comments, and future perspectives are also proposed. This review is expected to provide rewarding insights into the future development and broad application of pretreatment and detection methods for sweeteners in different food samples.

Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder / 中国中药杂志

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

mRNA delivery in cancer immunotherapy

Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.

Comparison of Functional Status Between Diabetic Patients With and Without Nephropathy Based on the International Classification of Functioning,Disability and Health Rehabilitation Set / 中国医学科学院学报

Objective To compare the functional status of diabetic patients with and without nephropathy and identify the items that diabetic patients with nephropathy are more likely to develop dysfunction than diabetic patients without nephropathy based on the international classification of functioning,disability and health rehabilitation set(ICF-RS).Methods A cross-sectional study was conducted.A total of 320 diabetic patients hospitalized in Guangdong Provincial Hospital of Chinese Medicine from August 2021 to February 2022 were selected and assigned into a group with nephropathy and a group without nephropathy.The general characteristics,clinical examination,and laboratory findings were compared by the t test,rank sum test,and Chi-squared test.The functional status of the patients was compared between the two groups by the t test based on the ICF-RS.Logistic regression was employed to control interferential factors between the two groups and identify the association between nephropathy and ICF-RS problematic items among diabetic patients.Results The diabetic patients with nephropathy had more problematic items in ICF-RS(P<0.001),the body function dimension(P=0.003),the activity dimension(P<0.001),and the participation dimension(P<0.001)than those without nephropathy.Moreover,the diabetic patients with nephropathy experienced severer problems in 5 body function items(energy and drive functions,sleep functions,sexual functions,exercise tolerance functions,and muscle power functions),10 activity items(transferring oneself,walking,moving around using equipment,moving around,washing oneself,caring for body parts,toileting,dressing,doing housework,and looking after one's health),and 4 participation items(using transportation,assisting others,basic interpersonal interactions,and recreation and leisure)(all P<0.05).The Logistic regression results showed that compared with the diabetic patients without nephropathy,the diabetic patients with nephropathy were more likely to develop problems in energy and drive functions(aOR=4.35,95%CI=1.28-14.79,P=0.019),emotional functions(aOR=1.88,95%CI=1.06-3.34,P=0.031),sexual functions(aOR=3.39,95%CI=1.82-6.34,P<0.001),moving around(aOR=3.11,95%CI=1.76-5.52,P<0.001),doing housework(aOR=17.48,95%CI=3.57-85.60,P<0.001),looking after one's health(aOR=1.97,95%CI=1.13-3.43,P=0.017),using transportation(aOR=2.59,95%CI=1.38-4.88,P=0.003),and recreation and leisure(aOR=2.52,95%CI=1.46-4.35,P<0.001).Conclusion Compared with the diabetic patients without nephropathy,the patients with nephropathy suffer more ICF-RS problematic items and are more likely to develop dysfunction in certain items in all the three dimensions.

An RNA-binding protein-related risk signature can predict the prognosis and tumor immunity of patients with testicular germ cell tumors.

BACKGROUND: The functions of RNA-binding proteins (RBPs) in the occurrence and development of tumors remain largely unexplored. We established a risk signature based on RBPs to predict the prognosis, tumor-related immunity, and treatment benefits of patients with testicular germ cell tumors (TGCTs). METHODS: A risk signature was built based on RBPs closely related to survival obtained from TGCT data in The Cancer Genome Atlas (TCGA) database. The ability of the signature to predict prognosis was analyzed by survival curves and Cox regression. The risk signature was validated using the Gene Expression Omnibus (GEO) database. The connection between tumor immunity and the risk score was evaluated. Risk score-related drug sensitivity and biofunctions were also explored. RESULTS: A risk signature including four selected RBP genes (PARP12, USB1, POLR2E and EED) was established. The prognosis of high-risk TGCT patients was worse than that of low-risk TGCT patients. The risk score was considered a critical factor closely related to prognosis, as determined via Cox regression, and was also closely associated with multiple characteristics of tumor immunity, chemotherapy drugs and biofunctions. CONCLUSION: The established risk signature including four selected RBPs in TGCTs could predict the prognosis, tumor-related immunity and treatment benefits of patients with TGCTs. Utilization of this signature could help clinicians make personalized treatment decisions.

An HDAC9-associated immune-related signature predicts bladder cancer prognosis.

BACKGROUND: The close relationship between histone deacetylase 9 (HDAC9) and immunity has attracted attention. We constructed an immune signature for HDAC9, a vital epigenetic modification, to predict the survival status and treatment benefits in bladder cancer (BC). METHODS: An exhaustive analysis of HDAC9 and immunology via the tumor and immune system interaction database (TISIDB) was performed, and an immune prognostic risk signature was developed based on genes enriched in the top five immune-related pathways under high HDAC9 status. Comprehensive analysis of survival curves and Cox regression were used to estimate the effectiveness of the risk signature. The relationship between immunological characteristics and the risk score was evaluated, and the mechanisms were also explored. RESULTS: In the TISIDB, HDAC9 was closely related to various immunological characteristics. The risk signature was obtained based on genes related to prognosis enriched in the top five immune-related pathways under high HDAC9 status. The survival rate of the high-risk BC patients was poor. The risk score was closely related to multiple immunological characteristics, drug sensitivity, immunotherapy benefits and biofunctions. CONCLUSION: An immune-related prognostic signature established for HDAC9 expression status could independently predict the prognosis of BC patients. The use of this signature could help clinicians make personalized treatment decisions.

[A new polyketide of endophytic fungi Aspergillus sp. ZJ-58 from Coptis chinensis].

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 µmol·L~(-1), suggesting its potential anti-inflammatory activity.

CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion.

CARD-containing MAGUK protein 3 (CARMA3) is associated with tumor occurrence and progression. However, the signaling pathways involved in CARMA3 function remain unclear. We aimed to analyze the association between CARMA3 and stathmin (STMN1) through the NF-κB pathway, which is associated with cell proliferation and invasion, in clear cell renal cell carcinoma (ccRCC). We evaluated the effects of CARMA3 and STMN1 expression on cell migration, proliferation, and invasion in various cell lines, and their expression in tissue samples from patients with ccRCC. CARMA3 was highly expressed in ccRCC tissues and cell lines. Moreover, CARMA3 promoted the proliferation and invasion of RCC cells by activating the NF-κB pathway to transcribe STMN1. Stathmin exhibited a consistent profile with CARMA3 in ccRCC tissue, and could be an effector for CARMA3-activated cell proliferation and invasion of ccRCC cells. In summary, CARMA3 may serve as a promising target for ccRCC treatment.

Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo

SARS-CoV-2 has rapidly become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. Here, we systematically investigated the untranslated regions (UTRs) of mRNAs in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, we identified the optimal combination of 5 and 3 UTR, termed as NASAR, which was five to ten-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived nanoparticles showed dramatic expression of potential SARS-CoV-2 antigens both in vitro and in vivo. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.

[Performance Study of Bromochloracetonitrile Degradation in Drinking Water by Fe/Cu Catalytic Reduction].

The paper used the method of iron copper catalyst reduction to degrade low concentrations of bromochloracetonitrile (BCAN) to lighten the damage to human being, which is a kind of disinfection by-products (DBPs) produced during the chlorination process of drinking water. The removal efficiency of BCAN and its influencing factors were investigated. The mechanism of degradation and kinetics were also explored. The results indicated that iron copper had a greater degradation ability towards BCAN, and the degradation rate of iron copper (mass ratio of 10:1) was 1.5 times that of the zero-valent iron. The removal of BCAN increased obviously with the increase of Fe/Cu dosage. When the initial concentration was set at 20 microg x L(-1), after a reaction time of 150 min, removal of BCAN was improved from 51.1% to 89.5% with the increase of iron copper (mass ratio of 10:1) dosage from 5 g x L(-1) to 10 g x L(-1). The temperature also had great impact on BCAN removal and the removal increased with the increase of temperature. However, BCAN removal did not change a lot with the variation of the initial concentration of BCAN when it was at a low level. The BCAN degradation by iron copper catalytic-reduction followed the first-order kinetics model.

EIF2C, Dicer, and Drosha are up-regulated along tumor progression and associated with poor prognosis in bladder carcinoma.

EIF2C, Dicer, and Drosha are microRNA-regulating machinery components, which participate in microRNA intracellular process and transfer. Our research demonstrated the expression and clinical role of the microRNA-regulating machinery in bladder cancer. EIF2C1, EIF2C2, Dicer, and Drosha mRNA and protein levels were analyzed in 100 bladder carcinomas and 50 normal bladder tissues using quantitative polymerase chain reaction and Western blotting. EIF2C2, Dicer, and Drosha mRNAs and proteins were overexpressed in carcinoma compared with normal tissues, whereas EIF2C1 mRNA and protein were not obviously different. Moreover, immunohistochemistry was used to detect the expressions of EIF2C2, Dicer, and Drosha in 100 bladder carcinomas. There were higher EIF2C2, Dicer, and Drosha expressions in carcinomas than in the adjacent normal tissues, positive correlations being noted with clinical stage, histopathologic grade, and recurrence. Higher EIF2C2, Dicer, and Drosha expressions were related to shorter cancer-specific survival and shorter recurrence-free survival. Multivariate Cox analysis showed that EIF2C2 was an important risk factor in bladder cancer. In conclusion, EIF2C2, Dicer, and Drosha are more highly expressed in bladder carcinoma, promote the development of bladder cancer, and suggested a poor prognosis. Their clinical role in bladder carcinoma merits further research.

hZIP1 that is down-regulated in clear cell renal cell carcinoma is negatively associated with the malignant potential of the tumor.

OBJECTIVE: The human ZRT, IRT-like protein 1 (hZIP1) has been associated with tumorigenesis. However, its role in clear cell renal cell carcinoma (ccRCC) has not been yet reported. The objective was to investigate hZIP1 expression in ccRCC and its association with clinicopathological features. MATERIALS AND METHODS: A total of 106 ccRCC tissue samples and corresponding normal kidney tissue samples were examined, along with 3 ccRCC cell lines (ACHN, 769-P, and 786-O). Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to investigate the expression of hZIP1 and its relationship with clinicopathological features. The ACHN cell line, exhibiting the highest hZIP1 expression, was transfected with hZIP1 small interfering RNA or mock small interfering RNA. Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion was determined by Transwell assay. RESULTS: The level of hZIP1 was decreased in ccRCC tissues when compared with normal tissues. hZIP1 expression significantly decreased with increasing clinical stage and pathological grade in ccRCC samples (P<0.05), showing a significant negative correlation with the histological grade (P<0.05). High hZIP1 expression was associated with a better disease-free survival (P<0.01). Silencing of hZIP1 expression enhanced the proliferative and invasive abilities of ACHN cells. CONCLUSIONS: Results suggest that hZIP1 may act as a tumor suppressor in ccRCC. hZIP1 is closely correlated with clinicopathological features. High hZIP1 expression may be an indicator of good prognosis in ccRCC.

A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway.

Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent.

Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid ß.

Accumulation of amyloid-ß (Aß) is a key event mediating the cognitive deficits in Alzheimer's disease (AD) as Aß promotes synaptic dysfunction and triggers neuronal death. Recent evidence has linked the hormone leptin to AD as leptin levels are markedly attenuated in AD patients. Leptin is also a potential cognitive enhancer as it facilitates the cellular events underlying hippocampal learning and memory. Here we show that leptin prevents the detrimental effects of Aß(1-42) on hippocampal long-term potentiation. Moreover leptin inhibits Aß(1-42)-driven facilitation of long-term depression and internalization of the 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA) receptor subunit, GluR1, via activation of PI3-kinase. Leptin also protects cortical neurons from Aß(1-42)-induced cell death by a signal transducer and activator of transcription-3 (STAT-3)-dependent mechanism. Furthermore, leptin inhibits Aß(1-42)-mediated upregulation of endophilin I and phosphorylated tau in vitro, whereas cortical levels of endophilin I and phosphorylated tau are enhanced in leptin-insensitive Zucker fa/fa rats. Thus leptin benefits the functional characteristics and viability of neurons that degenerate in AD. These novel findings establish that the leptin system is an important therapeutic target in neurodegenerative conditions.