Noninvasive Left Ventricular Pressure-Strain Loop for Quantitative Assessment of Early Left Ventricular Systolic Dysfunction in Patients With Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) possess a pronounced risk for cardiovascular events. A noninvasive left ventricular pressure-strain loop (LV-PSL) has recently been introduced to detect subtler changes in cardiac function. This study aims to investigate the value of LV-PSL for quantitative assessment of myocardial work (MW) in patients with CKD. METHODS: Seventy-five patients with CKD were enrolled retrospectively (37 patients with CKD Stages 2-3, and 38 patients with CKD Stages 4-5), and 35 healthy volunteers were included as controls. All subjects underwent transthoracic echocardiography. LV-PSL analysis was performed to estimate LV MW and efficiency. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by echocardiography, and the differences among the groups were compared. RESULTS: There was a significant increase in GWW and reduction in GWE in patients with CKD compared to normal controls (p < 0.05). No significant difference in GWI and GCW was observed among the three groups. Multiple linear regression revealed that increased GWW was significantly associated with age, serum creatinine, and systolic pressure, and decreased GWE was associated with age, serum creatinine, and GLS. CONCLUSION: LV-PSL can be used for noninvasive quantitative assessment of MW in patients with CKD, providing a new sensitive approach for the clinical assessment of myocardial function.

Impacting factors and sources of perceived stress by home-quarantined residents in Shanghai during COVID-19 epidemic.

BACKGROUND: Home-quarantine is one of the most common measures implemented to prevent or minimize the transmission of COVID-19 among communities. This study assessed stress levels of the home-quarantined residents in Shanghai during a massive wave of COVID-19 epidemic this year, explored the stress sources perceived by the respondents, and analyzed the association between each of the sociodemographic factors and the stress level. METHODS: This online survey was launched during April 23 - 30, 2022, the early stage of a massive wave of COVID-19 in Shanghai, China. Participants were quarantined-residents negative for COVID-19. They were asked to list some situations that were their major concerns and perceived stressful, in addition to sociodemographic and COVID-19 related information. Moreover, they were asked to complete the Perceived Stress Scale-14 (PSS-14) for the assessment of stress level. RESULTS: A total of 488 valid questionnaires were collected from 192 male and 296 female respondents. Overall, 207 persons (42.42%) presented high stress level (PSS-14 score ≥43). The top three concerns perceived stressful by respondents are "not allowed to go outdoors", "uncertain duration of the epidemic", and "lack of food supply". Fewer than 50% of the respondents perceived the other situations stressful. Higher proportions of young adults (≤ 29 years old), males, unemployed, singles, and those with low income (≤ 1999 yuan/month) perceived high stress compared to their counterparts, none of COVID-19 related factors is associated with the stress level, including location of residence, result of nucleic acid test, knowledge about COVID-19, whether vaccinated, and quarantine duration. CONCLUSION: Home-quarantine applied to people negative for COVID-19 led to a lot of major concerns that may be perceived stressful, whereas the virus-related factors did not show significant impact on mental health of the respondents.

A Sparse-Array Design Method Using Q Uniform Linear Arrays for Direction-of-Arrival Estimation.

Nowadays, sparse arrays have been a hotspot for research in the direction of arrival (DOA). In order to achieve a big value for degrees of freedom (DOFs) using spatial smoothing methods, researchers try to use multiple uniform linear arrays (ULAs) to construct sparse arrays. But, with the number of subarrays increasing, the complexity also increases. Hence, in this paper, a design method, named as the cross-coarray consecutive-connected (4C) criterion, and the sparse array using Q ULAs (SA-UQ) are proposed. We first analyze the virtual sensor distribution of SA-U2 and extend the conclusions to SA-UQ, which is the 4C criterion. Then, we give an algorithm to solve the displacement between subarrays under the given Q ULAs. At last, we consider a special case, SA-U3. Through the analysis of DOFs, SA-UQ can find underdetermined signals. Moreover, SA-U3 can obtain DOFs close to other sparse arrays using three ULAs. The simulation experiments prove the performance of SA-UQ.

A Mixed-Field Circular and Non-Circular Source Localization Algorithm Based on Exact Spatial Propagation Geometry.

In passive localization techniques, as the scale of the array of the sensors used increases, the source distribution may be a coexistence of near-field (NF) and far-field (FF) sources. Most of the existing algorithms dedicated to the localization of mixed-field sources are based on a simplified model, which has model errors and cannot make good use of non-circular properties when non-circular signals are present in the sources. In this paper, we present a mixed-field circular and non-circular source localization algorithm based on exact spatial propagation geometry. First, we make an initial estimate of the source parameters using exact spatial geometry relations. The MUSIC algorithm is then used in combination with the non-circular properties of the signal to achieve an accurate estimate. The algorithm does not lose performance due to model mismatch and is able to make good use of the non-circular properties of the sources to improve the estimation accuracy. The simulation results show that the proposed algorithm can effectively distinguish between sources and that the algorithm performs satisfactorily.

An L-Shaped Three-Level and Single Common Element Sparse Sensor Array for 2-D DOA Estimation.

The degree of freedom (DOF) is an important performance metric for evaluating the design of a sparse array structure. Designing novel sparse arrays with higher degrees of freedom, while ensuring that the array structure can be mathematically represented, is a crucial research direction in the field of direction of arrival (DOA) estimation. In this paper, we propose a novel L-shaped sparse sensor array by adjusting the physical placement of the sensors in the sparse array. The proposed L-shaped sparse array consists of two sets of three-level and single-element sparse arrays (TSESAs), which estimate the azimuth and elevation angles, respectively, through one-dimensional (1-D) spatial spectrum search. Each TSESA is composed of a uniform linear subarray and two sparse subarrays, with one single common element in the two sparse subarrays. Compared to existing L-shaped sparse arrays, the proposed array achieves higher degrees of freedom, up to 4Q1Q2+8Q1-5, when estimating DOA using the received signal covariance. To facilitate the correct matching of azimuth and elevation angles, the cross-covariance between the two TSESA arrays is utilized for estimation. By comparing and analyzing performance parameters with commonly used L-shaped and other sparse arrays, it is found that the proposed L-shaped TSESA has higher degrees of freedom and array aperture, leading to improved two-dimensional (2-D) DOA estimation results. Finally, simulation experiments validate the excellent performance of the L-shaped TSESA in 2-D DOA estimation.

Health effects of future dioxins emission mitigation from Chinese municipal solid waste incinerators.

Dioxins (including 2,3,7,8-tetrachlorodibenzo-p-dioxin, as Group 1 Carcinogen) in the atmosphere mainly originate from incomplete combustion during municipal solid waste (MSW) incineration. To significantly reduce dioxins emission from the MSW incineration industry, China has promulgated a set of ambitious plans regulating MSW-related pollution; however, the emission reduction potentials and concomitant environmental and health impacts associated with the implementation of these programs on a national scale remain unknown. Here, we use real measurements from official environmental impact assessment systems and continuous emissions monitoring systems (covering 96.6% of national MSW incinerators) to estimate unit-level dioxins emission and concomitant environmental and health impacts. We find that in 2018, 99.3% and 66.7% of Chinese incinerators met such concentration and temperature standards, respectively, controlling the total emissions to 19.6 g toxic equivalency quantity and maintaining carcinogenic and noncarcinogenic risks significantly below safety levels nationwide. Fully achieving both current standards and future regulations will reduce emissions and health risks by 67.7% and 62.6%, respectively, with waste sorting program contributing the majority. This study reveals substantial benefits from curbing MSW-related dioxins pollution and underscores the promise of ongoing management.

Plasma complement C3 and C3a are increased in major depressive disorder independent of childhood trauma.

BACKGROUND: Dysregulated complement system is linked to pathophysiology of major depressive disorder (MDD). Childhood trauma has been associated with an increased incidence of adult depression via a putative mechanism of immune activation. This study aimed to measure and compare peripheral levels of complement C3, C3a, C1q and C-reactive protein (CRP) in MDD patients and healthy controls and explore the relationship between these molecule levels and childhood trauma history in the participants. METHODS: The participants were 49 medication-free MDD patients and 45 healthy controls. All participants were asked to finish the Childhood Trauma Questionnaire, followed by blood sampling for measurement of plasma complement C3, C3a, C1q and CRP by means of enzyme-linked immunosorbent assay. RESULTS: Peripheral plasma concentration of C3 and C3a in medication-free MDD group was significantly higher than that in the healthy controls; whereas the concentration of plasma C1q and CRP in depressed patients was comparable to that in healthy controls. All these inflammatory factors were not associated to childhood trauma experience in patients with MDD. CONCLUSION: Our data suggest that complement C3 and C3a may be implicated in the pathophysiology of MDD, although traumatic childhood experiences were not associated with the circulating levels of complement C3, C3a, C1q and CRP.

Fibroblast growth factor 21 associating with serotonin and dopamine in the cerebrospinal fluid predicts impulsivity in healthy subjects.

BACKGROUND: Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects. METHODS: A total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits. RESULTS: Negative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity. CONCLUSIONS: FGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Agitation and apathy increase risk of dementia in psychiatric inpatients with late-onset psychiatric symptoms.

BACKGROUND: A diagnosis of dementia in middle-aged and elder people is often complicated by physical frailty and comorbid neuropsychiatric symptoms (NPSs). Previous studies have identified NPSs as a risk factor for dementia. The aim of this study was to figure out to what extent individual NPS and certain demographic factors increased the risk of dementia in middle-aged and senior psychiatric inpatients. METHODS: One hundred twenty-seven middle-aged and senior patients admitted to psychiatric wards for late-onset (age ≥ 50 years) psychiatric symptoms were included and categorized into dementia or non-demented psychiatric disorders (NDPD). The patients' demographic information and medical records were collected during the first hospitalization and subjected to statistical analyses. RESULTS: 41.73% of the registered psychiatric inpatients were diagnosed as dementia in which Alzheimer's disease (AD) was the dominant subtype. The NDPD group consisted of nine individual diagnoses, except for schizophrenia. The frequencies of dementia inpatients increased with first episode age while that of NDPD inpatients decreased with first episode age. In the enrolled inpatients, most of dementia patients were males while females accounted for a higher proportion of NDPD patients. 58.49% of enrolled dementia inpatients presented cognitive deficit (CD) as the initial symptom while the remaining 41.51% showed NPS as initial symptom. Of the 12 NPSs, agitation and apathy greatly and significantly increased risk of dementia in psychiatric inpatients with late-onset psychiatric symptoms. CONCLUSIONS: These results added evidence that the demented patients admitted to psychiatric ward are more likely to be male, older first episode age, and have characteristic NPS including aberrant motor behavior (AMB), hallucinations, agitation, irritability and apathy. Further, this study emphasized the importance of agitation and apathy of NPSs functioning as risk factors of dementia in these inpatients.

Aphid fecundity and defenses in wheat exposed to a combination of heat and drought stress.

Plants are routinely subjected simultaneously to different abiotic and biotic stresses, such as heat, drought, and insect infestation. Plant-insect interactions in such complex stress situations are poorly understood. We evaluated the performance of the grain aphid (Sitobion avenae) in wheat (Triticum aestivum L.) exposed to a combination of heat and drought stresses. We also performed assays of the relative water content, nutritional quality, and responses of phytohormone signaling pathways. Lower relative water content and accumulation of soluble sugars and amino acids were observed in plants exposed to combined heat and drought stress. These conditions increased abscisic acid levels in the absence of aphids, as well as leading to higher levels of jasmonate-dependent transcripts. The grain aphid infestation further increased abscisic acid levels and the abundance of jasmonic acid- and salicylic acid-dependent defenses under the combined stress conditions. Aphids reared on plants grown under drought stress alone showed lower net reproductive rates, intrinsic rates of increase, and finite rates of increase compared with aphids reared on plants in the absence of stress. The heat-treated plants also showed a decreased aphid net reproductive rate. These findings demonstrate that exposure to a combination of stresses enhances plant defense responses against aphids as well as altering nutritional quality.

Participatory mapping of cultural ecosystem services for landscape corridor planning: A case study of the Silk Roads corridor in Zhangye, China.

Cultural landscape corridors provide opportunities for recreation and other cultural ecosystem services (CES). Currently, many local governments are preparing cultural landscape corridor (CLC) proposals along China's Silk Roads, which include many notable features of historical human activity and communication between different cultures. However, public values and perceptions of these projects have been largely excluded from the planning processes. This study presents a spatial pattern analysis of public perceptions of the impact of a CLC in Zhangye, China. CES were used as a framework for participatory mapping, interviews, and a structured survey of public perceptions, and correspondence analysis was used to identify resident perceptions of the corridor's expected impact, especially as related to CES. Our results show that aesthetic values, cultural heritage values, and recreation were valued most highly. These values varied according to respondents' employment and land-use rights. The riverside was the most highest-valued area for CES. Respondents expressed concerns about the project's potentially negative impact, especially on the spiritual values of land. These concerns could be the source of conflict during project implementation. We conclude that linking participatory mapping with CES has the potential to improve corridor proposals and assist in the management of conflicts between planners and public stakeholders.

N-acetylcysteine attenuates the cuprizone-induced behavioral changes and oligodendrocyte loss in male C57BL/7 mice via its anti-inflammation actions.

Previous animal studies have linked white matter damage to certain schizophrenia-like behaviors in cuprizone (CPZ)-exposed mouse. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and oligodendrocyte loss coexist in the brain of such mice. The aim of this study was to examine effects of the antioxidant N-acetylcysteine (NAC) on CPZ-induced behavioral changes and concurrent oligodendrocyte loss, oxidative stress, and neuroinflammation in these animals. Male C57BL/6 mice were given intraperitoneal saline or NAC at doses of 100, 200, and 400 mg/kg/day for 2 weeks; animals were fed a CPZ-containing diet (0.2%, w/w) during days 5-14. During days 15-17, the mice were examined in open-field, social recognition, and Y-maze tests (1 test per day). Six mice in each group were then used for biochemical and enzyme-linked immunosorbent assay analyses, while the remaining animals were used for immunohistochemical and immunofluorescence staining. The mice exposed to CPZ for 10 days showed significantly lower spontaneous alternation in the Y-maze, lower activity of total superoxide dismutase, and glutathione peroxidase, but higher levels of malondialdehyde in the cerebral cortex and hippocampus, elevated concentrations of interleukin-1ß and tumor necrosis factor-α in the brain regions mentioned above and caudate putamen, and a decreased number of mature oligodendrocytes, but increased number of microglia in all the brain regions examined. These changes, however, were not seen or effectively alleviated in NAC-treated mice at all three doses. These results demonstrate that NAC protected mature oligodendrocytes against the toxic effects of CPZ, likely via its antioxidant and anti-inflammatory actions.

Two-Dimensional Direction-of-Arrival Fast Estimation of Multiple Signals with Matrix Completion Theory in Coprime Planar Array.

In estimating the two-dimensional (2D) direction-of-arrival (DOA) using a coprime planar array, the main issues are the high complexity of spectral peak search and the limited degree of freedom imposed by the number of sensors. In this paper, we present an algorithm based on the matrix completion theory in coprime planar array that reduces the computational complexity and obtains a high degree of freedom. The algorithm first analyzes the covariance matrix of received signals to estimate the covariance matrix of a virtual uniform rectangular array, which has the same aperture as the coprime planar array. Matrix completion theory is then applied to estimate the missing elements of the virtual array covariance matrix. Finally, a closed-form DOA solution is obtained using the unitary estimation signal parameters via rotational invariance techniques (Unitary-ESPRIT). Simulation results show that the proposed algorithm has a high degree of freedom, enabling the estimation of more signal DOAs than the number of sensors. The proposed algorithm has reduced computational complexity because the spectral peak search is replaced by Unitary-ESPRIT, but attains similarly high levels accuracy to those of the 2D multiple signal classification algorithm.

Direct Position Determination of Multiple Non-Circular Sources with a Moving Coprime Array.

Direct position determination (DPD) is currently a hot topic in wireless localization research as it is more accurate than traditional two-step positioning. However, current DPD algorithms are all based on uniform arrays, which have an insufficient degree of freedom and limited estimation accuracy. To improve the DPD accuracy, this paper introduces a coprime array to the position model of multiple non-circular sources with a moving array. To maximize the advantages of this coprime array, we reconstruct the covariance matrix by vectorization, apply a spatial smoothing technique, and converge the subspace data from each measuring position to establish the cost function. Finally, we obtain the position coordinates of the multiple non-circular sources. The complexity of the proposed method is computed and compared with that of other methods, and the Cramer⁻Rao lower bound of DPD for multiple sources with a moving coprime array, is derived. Theoretical analysis and simulation results show that the proposed algorithm is not only applicable to circular sources, but can also improve the positioning accuracy of non-circular sources. Compared with existing two-step positioning algorithms and DPD algorithms based on uniform linear arrays, the proposed technique offers a significant improvement in positioning accuracy with a slight increase in complexity.

Regulation of astrocyte pathology by fluoxetine prevents the deterioration of Alzheimer phenotypes in an APP/PS1 mouse model.

Studies have implicated astrocytic dysfunction in Alzheimer's disease (AD). However, the role of astrocytes in the pathophysiology and treatment of the disease is poorly characterized. Here, we identified astrocytes as independent key factors involved in several Alzheimer-like phenotypes in an APP/PS1 mouse model, including amyloid pathology, altered neuronal and synaptic properties, and impaired cognition. In vitro astrocytes from APP/PS1 mice induced synaptotoxicity as well as reduced dendritic complexity and axonal branching of hippocampal neurons. These astrocytes produced high levels of soluble ß-amyloid (Aß) which could be significantly inhibited by fluoxetine (FLX) via activating serotonin 5-HT2 receptors. FLX could also protect hippocampal neurons against astrocyte-induced neuronal damage in vitro. In the same APP/PS1 mice, FLX inhibited activation of astrocytes, lowered Aß products, ameliorated neurotoxicity, and improved behavioral performance. These findings may provide a basis for the clinical application of FLX in patients, and may also lay the groundwork for exploration of other novel astrocyte-based therapies of AD.

Differential neurometabolite alterations in brains of medication-free individuals with bipolar disorder and those with unipolar depression: a two-dimensional proton magnetic resonance spectroscopy study.

OBJECTIVES: Bipolar disorder (BD) is a mental disorder characterized by periods of elevated mood and depression. Many individuals with BD are initially misdiagnosed and treated for unipolar depression (UD). In this study, we report direct comparisons between medication-free individuals with BD and those with UD in terms of the neurometabolites in the anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), parietal cortex (PC), and posterior cingulate cortex (PCC) of the brain. METHODS: Participants included medication-free patients with BD or UD, and matched healthy controls. All patients were in the depressive state and had similar symptoms. All subjects were subjected to a multi-voxel proton magnetic resonance spectroscopy procedure with a 3.0 T GE Signa MR scanner. After post-processing, the absolute concentrations of glycerophosphocholine + phosphocholine (GPC + PC), phosphocreatine + creatine (PCr + Cr), Glx (glutamate + glutamine), myo-inositol (MI), and N-acetyl aspartate (NAA) from the above brain regions were compared across the three groups. RESULTS: Patients with BD showed significantly higher levels of Glx in their ACC, lower GPC + PC, PCr + Cr, MI, and NAA in their PC, and lower NAA in their mPFC, compared to healthy controls; patients with UD presented significantly lower levels of GPC + PC, PCr + Cr, and NAA in their PCC, and lower Glx in their mPFC. All analyzed brain metabolites, except Glx, were significantly lower in the PC of patients with BD, whereas levels of GPC + PC, PCr + Cr, and NAA were significantly reduced in the PCC of patients with UD. CONCLUSIONS: These results add to the evidence of brain metabolite differences in brains of patients with UD and BD which may be of help in differentiating these two mood disorders.

Brain metabolite changes in subcortical regions after exposure to cuprizone for 6 weeks: potential implications for schizophrenia.

Cuprizone is a copper chelating agent able to selectively damage the white matter in the mouse brain. Recent studies have reported behavioral abnormalities relevant to some of schizophrenia symptoms. While associating white matter damage to the behavioral abnormalities, these previous studies did not rule out the possible impairment in neuronal functions in cuprizone-exposed mice. The aim of this study was to examine brain metabolites of the cuprizone-exposed mice by proton magnetic resonance spectroscopy ((1)H-MRS). The examined brain regions were the caudoputamen, midbrain, and thalamus; these subcortical regions showed different susceptibilities to cuprizone in terms of demyelination and oligodendrocyte loss in previous studies. Young C57BL/6 mice were fed a standard rodent chow without or with cuprizone (0.2 %) for 6 weeks. At the end, open-field and Y-maze tests were performed to measure the emotional and cognitive behaviors of the animals, followed by (1)H-MRS procedure to evaluate the brain metabolites. Cuprizone-exposure increased anxiety levels and impaired spatial working memory. The same treatment increased T2 signal intensity in the cerebral cortex, hippocampus, and caudoputamen, but not in the thalamus. Cuprizone-exposure decreased the concentrations of NAA and NAA+NAAG in caudoputamen, but not in thalamus and midbrain. It decreased levels of Cr+PCr, GPC+PCh and myo-inositol in all the three brain regions. These results provided neurochemical evidence for the impairment in neuronal functions by cuprizone treatment.

Differential effects of antipsychotics on the development of rat oligodendrocyte precursor cells exposed to cuprizone.

Cuprizone (CPZ) is a copper-chelating agent and has been shown to induce white matter damage in mice and rats. The compromised white matter and oligodendrocytes (OLs) respond to some antipsychotics in vivo. However, little is known about the effects of antipsychotics on cultured OLs in the presence of CPZ. The aim of this study was to examine effects of some antipsychotics on developing OLs in the presence of CPZ. Oligodendrocyte progenitor cells (OPCs) were prepared from rat embryos; OLs at different developing stages were labeled with specific antibodies; levels of CNP and MBP proteins in mature OLs were assessed by Western-blot analysis; malondialdehyde (MDA) levels and activity of catalase were evaluated as well for an assessment of oxidative stress and antioxidative status. In immunofluorescent staining, CPZ was shown to inhibit the differentiation of cultured OPCs into O4-positive cells, reduce the maturation of O4-positive cells into CNP- and MBP-positive cells, and decrease levels of CNP and MBP in mature OLs. These inhibitory effects of CPZ were ameliorated by clozapine and quetiapine (QUE), but not by haloperidol and olanzapine. Further experiments were performed to explore the mechanism of the protective effects of QUE. QUE attenuated the decreases in CNP and MBP in CPZ-treated OLs, and blocked the CPZ-induced increase in MDA and decrease in catalase activity in cultured OLs. These results are relevant to the pathophysiology and treatment of schizophrenia considering the aberrant white matter development and evidence suggesting the derangement of the oxidant and antioxidant defense system in some of the patients with schizophrenia.

Changes in metabolic hormones and trace elements in CSF in active smokers indicate oxidative damage to brain cells.

Objective: This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism. Methods: A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed. Results: Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers. Conclusion: These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease.

Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aß deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aß deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.