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Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.
We sought to assess the degree to which environmental risk factors affect CHD prevalence using a case–control study.
Methods:
A hospital-based study was conducted by collecting data from outpatients between January 2016 and January 2021, which included 31 CHD cases and 72 controls from eastern China. Risk ratios were estimated using univariate and multivariate logistic regression models and mediating effect analysis.
Results:
Residential characteristics (usage of cement flooring, odds ratio = 17.04[1.954–148.574], P = 0.01; musty smell, odds ratio = 3.105[1.198–8.051], P = 0.02) and indoor total volatile organic compound levels of participants’ room (odds ratio = 31.846[8.187–123.872, P < 0.001), benzene level (odds ratio = 7.370[2.289–23.726], P = 0.001) increased the risk of CHDs in offspring. And folic acid plays a masking effect, which mitigates the affection of the total volatile organic compound (indirect effect = -0.072[−0.138,-0.033]) and formaldehyde (indirect effect = −0.109[-0.381,-0.006]) levels on the incidence of CHDs. While food intake including milk (odds ratio = 0.396[0.16–0.977], P = 0.044), sea fish (odds ratio = 0.273[0.086–0.867], P = 0.028), and wheat (odds ratio = 0.390[0.154–0.990], P = 0.048) were all protective factors for the occurrence of CHDs. Factors including women reproductive history (history of conception control, odds ratio = 2.648[1.062–6.603], P = 0.037; history of threatened abortion, odds ratio = 2.632[1.005–6.894], P = 0.049; history of dysmenorrhoea (odds ratio = 2.720[1.075–6.878], P = 0.035); sleep status (napping habit during daytime, odds ratio = 0.856[0.355–2.063], P = 0.047; poor sleep quality, odds ratio = 3.180[1.037–9.754], P = 0.043); and work status (working time > 40h weekly, odds ratio = 2.882[1.172–7.086], P = 0.021) also influenced the CHDs incidence to differing degrees.
Conclusion:
Diet habits, nutrients intake, psychological status of pregnant women, and residential air quality were associated with fetal CHDs. Indoor total volatile organic compound content was significantly correlated with CHDs risk, and folic acid may serve as a masking factor that reduce the harmful effects of air pollutants.
Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1’s analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.
Methods:
A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.
Results:
Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.
Discussion:
Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.
Methods:
We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.
Results:
GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.
Discussion:
GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterised by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.
The emotion regulation network (ERN) in the brain provides a framework for understanding the neuropathology of affective disorders. Although previous neuroimaging studies have investigated the neurobiological correlates of the ERN in major depressive disorder (MDD), whether patients with MDD exhibit abnormal functional connectivity (FC) patterns in the ERN and whether the abnormal FC in the ERN can serve as a therapeutic response signature remain unclear.
Methods
A large functional magnetic resonance imaging dataset comprising 709 patients with MDD and 725 healthy controls (HCs) recruited across five sites was analyzed. Using a seed-based FC approach, we first investigated the group differences in whole-brain resting-state FC of the 14 ERN seeds between participants with and without MDD. Furthermore, an independent sample (45 MDD patients) was used to evaluate the relationship between the aforementioned abnormal FC in the ERN and symptom improvement after 8 weeks of antidepressant monotherapy.
Results
Compared to the HCs, patients with MDD exhibited aberrant FC between 7 ERN seeds and several cortical and subcortical areas, including the bilateral middle temporal gyrus, bilateral occipital gyrus, right thalamus, calcarine cortex, middle frontal gyrus, and the bilateral superior temporal gyrus. In an independent sample, these aberrant FCs in the ERN were negatively correlated with the reduction rate of the HAMD17 score among MDD patients.
Conclusions
These results might extend our understanding of the neurobiological underpinnings underlying unadaptable or inflexible emotional processing in MDD patients and help to elucidate the mechanisms of therapeutic response.
Embodiment theories postulate that language processing inherently engages the sensorimotor system. This study explores the embodiment of action verbs in the second language (L2) and the effects of various L2 experiences (L2 age of acquisition, exposure, dominance, and proficiency) on L2 embodiment. Sixty-one Chinese–English bilinguals participated in two experiments judging semantic relatedness: Experiment 1 involved verb–picture pairs, while Experiment 2 focused on verb–verb pairs. Both experiments were conducted in the participants’ first language (Chinese) and second language (English), with the stimuli depicting actions performed by specific effectors (e.g., mouth, hand, and foot). Results showed that participants took longer to reject mismatched verb–picture pairs and semantic-unrelated verb–verb pairs when the actions shared the same effector (e.g., walk–run) than those involving different effectors (e.g., eat–touch). Moreover, L2 age of acquisition, exposure, and dominance correlated with the L2 embodiment effect, with L2 age of acquisition and exposure modulating this effect. This study enhances our understanding of L2 embodied semantics and illuminates the impact of multidimensional L2 experiences on embodiment.
This study aimed to explore the influence of laryngopharyngeal reflux on the features of vocal fold polyps and prognosis after office-based transnasal vocal fold polypectomy.
Methods
Eighty-four vocal fold polyp patients were retrospectively analysed. Patients were assigned to laryngopharyngeal reflux or non-laryngopharyngeal reflux groups using pre-operative Reflux Symptom Score-12.
Results
The laryngopharyngeal reflux group had significantly higher pre-operative Reflux Sign Assessment scores, worse lifestyle and worse eating habits than the non-laryngopharyngeal reflux group. After office-based transnasal vocal fold polypectomy, the Reflux Symptom Score-12 and Reflux Sign Assessment score decreased in both groups, although the laryngopharyngeal reflux group still had higher values. The non-laryngopharyngeal reflux group had better vocal fold morphology recovery than the laryngopharyngeal reflux group. Multivariate logistic regression analysis demonstrated that smoking and a higher pre-operative Reflux Symptom Score-12 score were independent risk factors for poor prognosis.
Conclusions
Laryngopharyngeal reflux is detrimental to vocal fold recovery of vocal fold polyp patients following office-based transnasal vocal fold polypectomy. For vocal fold polyp patients with laryngopharyngeal reflux, lifestyle and diet guidance should be focused.
This study aimed to assess the relationship between COVID-19 infection-related conditions and depressive symptoms among medical staff after easing the zero-COVID policy in China, and to further examine the mediating role of professional burnout.
Methods
A total of 1716 medical staff from all levels of health care institutions in 16 administrative districts of Beijing, China, were recruited to participate at the end of 2022 in this cross-sectional study. Several multiple linear regressions and mediating effects tests were performed to analyze the data.
Results
At the beginning of the end of the zero-COVID policy in China, 91.84% of respondents reported infection with COVID-19. After adjusting for potential confounding variables, the severity of infection symptoms was significantly positively associated with high levels of depressive symptoms (β = 0.06, P < 0.001), and this association was partially mediated by professional burnout. Specifically, emotional exhaustion (95% CI, 0.131, 0.251) and depersonalization (95% CI, 0.009, 0.043) significantly mediated the association between the severity of infection symptoms and depressive symptoms.
Conclusions
The mental health of medical staff with more severe symptoms of COVID-19 infection should be closely monitored. Also, interventions aimed at reducing emotional exhaustion and depersonalization may effectively reduce their risk of developing depressive symptoms.
Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG.
Methods
Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria.
Results
We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis.
Conclusion
Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.
For $r\in(0,1)$, let $\mu \left( r\right) $ be the modulus of the plane Grötzsch ring $\mathbb{B}^2\setminus[0,r]$, where $\mathbb{B}^2$ is the unit disk. In this paper, we prove that
with $\theta _{n}\in \left( 0,1\right)$. Employing this series expansion, we obtain several absolutely monotonic and (logarithmically) completely monotonic functions involving $\mu \left( r\right) $, which yields some new results and extend certain known ones. Moreover, we give an affirmative answer to the conjecture proposed by Alzer and Richards in H. Alzer and K. Richards, On the modulus of the Grötzsch ring, J. Math. Anal. Appl. 432(1): (2015), 134–141, DOI 10.1016/j.jmaa.2015.06.057. As applications, several new sharp bounds and functional inequalities for $\mu \left( r\right) $ are established.
Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
To explore the associations between nutrition literacy (NL) and possible sarcopenia in older Chinese adults. A cross-sectional study was conducted. NL was assessed using a twelve-item short-form NL scale. Possible sarcopenia was identified using SARC-CALF. Logistic regression was used to calculate OR and 95 % CI for NL and the incidence of possible sarcopenia. A total of 1338 older individuals, aged 71·41 (sd 6·84) years, were enrolled in this study. After confounders were adjusted for, older adults in the upper quartile of NL were found to be 52 % less likely to have possible sarcopenia than those in the lower quartile of NL (OR = 0·48, 95 % CI: 0·29, 0·77). The associations between NL and possible sarcopenia were present only in those who lived in rural areas (OR: 0·38, 95 % CI: 0·19, 0·77), had a primary school education or less (OR: 0·21, 95 % CI: 0·09, 0·48), had a monthly income < 3000 RMB (OR: 0·39, 95 % CI: 0·22, 0·70) and had chronic diseases (OR: 0·37, 95 % CI: 0·22, 0·63). Moreover, an interaction effect was observed between having a chronic disease and junior high school education and being in the upper quartile of NL. The prevalence of possible sarcopenia in older Chinese adults is substantial, with prevalence decreasing with increasing NL. Moreover, the association between NL and possible sarcopenia varies by residence type, education level, monthly income and chronic disease experience. Targeted NL interventions are required to prevent and manage sarcopenia in older adults, particularly those with low socio-economic status and chronic diseases.
Pi-d2, which encodes a potential serine-threonine receptor-like kinase (RLK) membrane-spanning protein consisting of 825 amino acids, confers resistance to Magnaporthe oryzae strain ZB15 via an unidentified recognition mechanism. In this study, the Pid2 alleles of 303 rice (O. sativa) varieties from China's Yunnan region were amplified and sequenced in order to produce 24 haplotypes and 16 translation variants. Six of twenty-four alleles possessing the resistant site at the 441st amino acid were chosen for evaluating blast resistance by transforming into the blast-vulnerable rice variety Nipponbare. After being infected with 11 strains of M. oryzae, all transgenic lines exhibited resistance to ZB-15, whereas resistance to other strains varied. Notably, Pi-d2_H23 and Pi-d2_H24 exhibited resistance to all M. oryzae strains tested, indicating that these two alleles may have a broader resistance spectrum to M. oryzae. Alignment of these alleles’ amino acid sequences revealed that the differences in blast resistance spectra were primarily related to the amino acids present in the PAN domain at position 363 (valine/alanine). These findings suggested that the two extracellular signal recognition domains of PI-D2, B-lectin and PAN, may play a role in the identification of M. oryzae effectors. The present results provide insight into the mechanism of interaction between RLKs and M. oryzae.
This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.
Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children’s Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1–4 years exhibited higher risk of PTB and TB meningitis, and children aged 5–12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.
Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear.
Methods
We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed.
Results
The GS fluctuations were reduced in patients with MDD across the full frequency range (0–0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728–0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group.
Conclusion
The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.
The efficient separation of hexane isomers from the light naphtha fraction is a significant challenge in the petrochemical industry. 5A zeolite adsorbent is used commercially to sieve alkane isomers. In this study, 5A zeolites were synthesized using a low-cost natural clay mineral precursor, i.e. palygorskite (PAL), with the addition of crystallization directing agent (CDA). By varying the mass ratio of CDA/deionized water, 5A zeolites were obtained as CDA-5%, CDA-7.5%, and CDA-10%. All products were submicron particles with an average particle size of 400–800 nm. A sieving test of CDA-induced 5A zeolites was carried out on hexane adsorbates including n-hexane (nHEX), 2-methylpentane (2MP), and 3-methylpentane (3MP). According to vapor-phase batch adsorption experiments, a significant equilibrium amount (0.149 g/g) of nHEX and only 0.0321 g/g 2MP and 0.0416 g/g 3MP were adsorbed on the 5A zeolite product with CDA-5%. The dynamic adsorption performance of 5A zeolite (CDA-5%) was evaluated by breakthrough curves of binary mixtures of nHEX/2MP and nHEX/3MP. Palygorskite 5A (PAL 5A) zeolite achieved maximum dynamic adsorption capacities of nHEX (0.16 g/g in both cases) at 200°C and 1.2 MPa total pressure. This work provided an economic alternative for the synthesis of 5A zeolites using natural clay minerals instead of chemical raw materials.