Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity.

Common genetic variants and susceptibility loci associated with Alzheimer's disease (AD) have been discovered through large-scale genome-wide association studies (GWAS), GWAS by proxy (GWAX) and meta-analysis of GWAS and GWAX (GWAS+GWAX). However, due to the very low repeatability of AD susceptibility loci and the low heritability of AD, these AD genetic findings have been questioned. We summarize AD genetic findings from the past 10 years and provide a new interpretation of these findings in the context of statistical heterogeneity. We discovered that only 17% of AD risk loci demonstrated reproducibility with a genome-wide significance of P < 5.00E-08 across all AD GWAS and GWAS+GWAX datasets. We highlighted that the AD GWAS+GWAX with the largest sample size failed to identify the most significant signals, the maximum number of genome-wide significant genetic variants or maximum heritability. Additionally, we identified widespread statistical heterogeneity in AD GWAS+GWAX datasets, but not in AD GWAS datasets. We consider that statistical heterogeneity may have attenuated the statistical power in AD GWAS+GWAX and may contribute to explaining the low repeatability (17%) of genome-wide significant AD susceptibility loci and the decreased AD heritability (40-2%) as the sample size increased. Importantly, evidence supports the idea that a decrease in statistical heterogeneity facilitates the identification of genome-wide significant genetic loci and contributes to an increase in AD heritability. Collectively, current AD GWAX and GWAS+GWAX findings should be meticulously assessed and warrant additional investigation, and AD GWAS+GWAX should employ multiple meta-analysis methods, such as random-effects inverse variance-weighted meta-analysis, which is designed specifically for statistical heterogeneity.

Semiconservative transmission of DNA N6-adenine methylation in a unicellular eukaryote.

While DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, 6mA transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA in Tetrahymena thermophila In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2'-deoxyuridine (BrdU). In ΔAMT1 cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, while de novo methylation in ΔAMT1 cells is slow and sporadic. In Tetrahymena, regularly spaced 6mA clusters coincide with linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with striking similarity to 5-methyl cytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark.

Efficacy of repetitive transcranial magnetic stimulation in post-stroke cognitive impairment: an overview of systematic reviews.

Objective: The reliability of clinical evidence depends on high-quality meta-analyses/ systematic reviews (MAs/SRs). However, there has been no assessment of the quality of MAs/SRs for repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI), both nationally and internationally. This article seeks to use radar plotting to visually present the quality of MAs/SRs on rTMS for improving cognitive function in PSCI, aiming to offer an intuitive foundation for clinical research. Methods: Eight Chinese or English databases were systematically searched to collect comprehensive literature, and the retrieval time ranged from inception to 26 March 2024. Literature ranking was calculated using six dimensions: publication year, design type, AMSTAR-2 score, PRISMA score, publication bias, and homogeneity. Finally, radar plots were drafted to present a multivariate literature evaluation. The GRADE tool assessed the strength of evidence for the outcome indicators included in the MAs/SRs. Results: The 17 articles included had average scores of 12.29, 17, 9.88, 9.71, 12.88, and 12.76 for each dimension. The radar plot showed that an article published in 2023 had the highest rank and a large radar plot area, while an article published in 2021 had the lowest rank and a small radar plot area. The GRADE tool evaluation revealed that 51 pieces of evidence were of very low quality, 67 were of low quality, 12 were of moderate quality, and only one was of high quality. Conclusion: The average rank score of literature ranged from 8.50 to 17, with higher rankings indicating greater significance in literature reference. Variations in literature quality were attributed to inadequate study planning, irregular literature search and screening, insufficient description of inclusion criteria for studies, and inadequate consideration of bias risk in the included studies. Most MAs/SRs indicated that rTMS was more effective than the control group in enhancing the global cognitive function and activities of daily living in PSCI patients. However, the overall quality of the literature was generally low and needs validation from future high-quality evidence.Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023491280.

Neural basis of language familiarity effects on voice recognition: An fNIRS study.

Recognizing talkers' identity via speech is an important social skill in interpersonal interaction. Behavioral evidence has shown that listeners can identify better the voices of their native language than those of a non-native language, which is known as the language familiarity effect (LFE). However, its underlying neural mechanisms remain unclear. This study therefore investigated how the LFE occurs at the neural level by employing functional near-infrared spectroscopy (fNIRS). Late unbalanced bilinguals were first asked to learn to associate strangers' voices with their identities and then tested for recognizing the talkers' identities based on their voices speaking a language either highly familiar (i.e., native language Chinese), or moderately familiar (i.e., second language English), or completely unfamiliar (i.e., Ewe) to participants. Participants identified talkers the most accurately in Chinese and the least accurately in Ewe. Talker identification was quicker in Chinese than in English and Ewe but reaction time did not differ between the two non-native languages. At the neural level, recognizing voices speaking Chinese relative to English/Ewe produced less activity in the inferior frontal gyrus, precentral/postcentral gyrus, supramarginal gyrus, and superior temporal sulcus/gyrus while no difference was found between English and Ewe, indicating facilitation of voice identification by the automatic phonological encoding in the native language. These findings shed new light on the interrelations between language ability and voice recognition, revealing that the brain activation pattern of the LFE depends on the automaticity of language processing.

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer.

BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

CD200R promotes high glucose-induced oxidative stress and damage in human retinal pigment epithelial cells by activating the mTOR signaling pathway.

Diabetic retinopathy (DR) is established as the primary cause of visual impairment and preventable blindness, posing significant social and economic burdens on healthcare systems worldwide. Oxidative stress has been identified as a major contributor to DR, yet the precise role of the transmembrane glycoprotein CD200R in this context remains elusive. We studied human retinal pigment epithelia ARPE-19 cells to investigate the role of CD200R in high-glucose (HG) induced oxidative stress. Under HG conditions, we found a significant increase in CD200R expression in a time-dependent pattern. Conversely, knockdown of CD200R effectively alleviated oxidative stress and restored cell viability in HG-treated ARPE-19 cells, a phenomenon corroborated by the addition of a reactive oxygen species (ROS) scavenger. Exploration of the AKT/mTOR signaling pathway confirmed its mediating role regarding CD200R knockdown suppression of the expression of key proteins induced by HG conditions. Additionally, we found that the inhibition of mTOR signaling with Rapamycin effectively countered HG-induced oxidative stress in ARPE-19 cells, suggesting a promising therapeutic target against oxidative stress in the context of DR. This study establishes the crucial role of CD200R in HG-induced oxidative stress and identifies potential therapeutic avenues for the treatment of DR.

Prognostic nomogram based on pre-treatment HALP score for patients with advanced non-small cell lung cancer.

BACKGROUND: To explore the correlation of pre-treatment Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score with the prognosis of patients with advanced Non-Small Cell Lung Cancer (NSCLC) undergoing first-line conventional platinum-based chemotherapy. METHODS: In this retrospective cohort study, 203 patients with advanced NSCLC were recruited from January 2017 to December 2021. The cut-off value for the HALP score was determined by Receiver Operating Characteristic (ROC) curve analysis. The baseline characteristics and blood parameters were recorded, and the Log-rank test and Kaplan-Meier curves were applied for the survival analysis. In the univariate and multivariate analyses, the Cox regression analysis was carried out. The predictive accuracy and discriminative ability of the nomogram were determined by the Concordance index (C-index) and calibration curve and compared with a single HALP score by ROC curve analysis. RESULTS: The optimal cut-off value for the HALP score was 28.02. The lower HALP score was closely associated with poorer Progression-Free Survival (PFS) and Overall Survival (OS). The male gender and other pathological types were associated with shorter OS. Disease progression and low HALP were correlated with shorter OS and PFS. In addition, nomograms were established based on HALP scores, gender, pathology type and efficacy rating, and used to predict OS. The C-index for OS prediction was 0.7036 (95% CI 0.643 to 0.7643), which was significantly higher than the C-index of HALP at 6-, 12-, and 24-months. CONCLUSION: The HALP score is associated with the prognosis of advanced NSCLC patients receiving conventional platinum-based chemotherapy, and the nomogram established based on the HALP score has a better predictive capability for OS.

Sensitive and effective method with 96-well plate for determination of levamlodipine in human plasma using LC-MS/MS.

we developed an effective protein precipitation method for determination of levamlodipine in human plasma using LC-MS/MS. Sample extraction was carried out by using liquid-liquid extraction in 96-well plate format. (S)-Amlodipine-d4 was used as internal standard (IS). The chromatographic separation was achieved using Philomen Chiral MX (2) column (3 µm, 2.1 × 100 mm). Mobile phase A was comprised of Acetonitrile (ACN), Mono ethanol amine (MEA) and Iso-Propyl alcohol (IPA) (1000:1:10, v/v/v), Mobile phase B was IPA-ACN (2:1, v/v). The flow rate was 0.4 mL/min. The total run time of each sample was 4.0 min with gradient elution. LC-MS/MS spectra were generated in positive ion mode, and multiple reaction monitoring (MRM) was used to detect the following transitions: m/z 409.20 â†’ 238.15 for levamlodipine and 415.25 â†’ 240.20 for (S)-Amlodipine-d4 (the IS). The method was linear from 50 to 10000 pg/mL（R2＝0.9988489）,and the lower limit of quantification (LLOQ) was 50 pg/mL. This method was applied to a bioequivalence study of levamlodipine.

Oxygen vacancy engineering of ultra-small CuWO4 nanoparticles for boosting photocatalytic organic pollutant degradation.

Nanomaterials have attracted great interest in the field of photocatalytic degradation due to their larger specific surface area and efficient charge/mass transfer ability, which are beneficial for enhancing photocatalytic activity. However, the bandgap of photocatalysts would increase with the size reduction, weakening the photoabsorption ability. Thus the relationship between the size of catalysts and photoactivity should be balanced to achieve optimal photocatalytic performance. Herein, ultra-small CuWO4 nanoparticles (ca. 39 nm) with moderate oxygen vacancies (CuWO4-OVs) were synthesized by the cascade strategy (ligand confinement@fast calcination). The introduction of oxygen vacancies offset the deficiency of light absorption ability caused by the small size effect. Besides, oxygen vacancies could provide more reaction active sites, conducive to the adsorption and activation of dye molecules and H2O. Degradation experiments reveal that the optimized photocatalyst CuWO4-OVs 350 shows outstanding photocatalytic activity, and the removal ratio of methylene blue (MB) reaches over 90.26% in 70 min, exceeding that of pure CuWO4-air (37.66%). Additionally, the degradation performance of CuWO4-OVs 350 surpasses most of the other CuWO4-based photocatalytic systems. More importantly, the photocatalytic degradation activity of CuWO4-OVs 350 could remain at 88.26% even after five cycles, and high photostability was achieved. This work affords constructive inspiration for synergistic photoactivity enhancement and increase of catalyst reaction active sites to achieve eminent photocatalytic degradation performance.

Better Rough than Scarce: Proximal Femur Fracture Segmentation with Rough Annotations.

Proximal femoral fracture segmentation in computed tomography (CT) is essential in the preoperative planning of orthopedic surgeons. Recently, numerous deep learning-based approaches have been proposed for segmenting various structures within CT scans. Nevertheless, distinguishing various attributes between fracture fragments and soft tissue regions in CT scans frequently poses challenges, which have received comparatively limited research attention. Besides, the cornerstone of contemporary deep learning methodologies is the availability of annotated data, while detailed CT annotations remain scarce. To address the challenge, we propose a novel weakly-supervised framework, namely Rough Turbo Net (RT-Net), for the segmentation of proximal femoral fractures. We emphasize the utilization of human resources to produce rough annotations on a substantial scale, as opposed to relying on limited fine-grained annotations that demand a substantial time to create. In RT-Net, rough annotations pose fractured-region constraints, which have demonstrated significant efficacy in enhancing the accuracy of the network. Conversely, the fine annotations can provide more details for recognizing edges and soft tissues. Besides, we design a spatial adaptive attention module (SAAM) that adapts to the spatial distribution of the fracture regions and align feature in each decoder. Moreover, we propose a fine-edge loss which is applied through an edge discrimination network to penalize the absence or imprecision edge features. Extensive quantitative and qualitative experiments demonstrate the superiority of RT-Net to state-of-the-art approaches. Furthermore, additional experiments show that RT-Net has the capability to produce pseudo labels for raw CT images that can further improve fracture segmentation performance and has the potential to improve segmentation performance on public datasets. The code is available at: https://github.com/zyairelu/RT-Net.

The crucial relationship between miRNA-27 and CSE/H2S, and the mechanism of action of GLP-1 in myocardial hypertrophy.

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.

Sustainable treatment of aquaculture water employing fungi-microalgae consortium: Nutrients removal enhancement, bacterial communities optimization, emerging contaminants elimination, and mechanism analysis.

Fungi-microalgae consortium (FMC) has emerged as a promising system for advanced wastewater treatment due to its high biomass yield and environmental sustainability. This study aimed to investigate the nutrients removal, bacterial community shift, emerging contaminants elimination, and treatment mechanism of a FMC composed of Cordyceps militaris and Navicula seminulum for aquaculture pond water treatment. The fungi and microalgae were cultured and employed either alone or in combination to evaluate the treatment performance. The results demonstrated that the FMC could improve water quality more significantly by reducing nutrient pollutants and optimizing the bacterial community structures. Furthermore, it exhibited stronger positive correlation between the enrichment of functional bacteria for water quality improvement and pollutants removal performance than the single-species treatments. Moreover, the FMC outperformed other groups in eliminating emerging contaminants such as heavy metals, antibiotics, and pathogenic Vibrios. Superiorly, the FMC also showed excellent symbiotic interactions and cooperative mechanisms for pollutants removal. The results collectively corroborated the feasibility and sustainability of using C. militaris and N. seminulum for treating aquaculture water, and the FMC would produce more mutualistic benefits and synergistic effects than single-species treatments.

Re-analysis of single-cell RNA-seq data reveals the origin and roles of cycling myeloid cells.

Cycling myeloid cells (CMCs) are often detected from various tissues using single-cell RNA sequencing (scRNA-seq) datasets, however, their research value was not noticed before. For the first time, our study preliminarily revealed the origin, differentiation, and roles of CMCs in physiological processes. Particularly, subgroup a of cycling myeloid cells (aCMCs) were conclusively identified as belonging to a specific cell type. In an active state, aCMCs rapidly proliferate during the early stages of an embryonic development. With an individual maturing, most aCMCs differentiate into specialized cells, while a small portion of them enter an inactive or dormant state. Under pathological conditions, aCMCs restore their proliferative and differentiation capacities via activation or revival. The present study has set the stage for future research on CMCs by linking them with progenitors of immune cells, and provided a crucial starting point to understand the origin, differentiation, and roles of CMCs in various physiological and pathological processes, particularly those related to traumatic injury, cancer, and pathogen infection, leading to develop targeted therapies or interventions.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Effect of polydimethylsiloxane on the structure and barrier properties of starch/PBAT composite films.

This study aimed to investigate the effects of polydimethylsiloxane (PDMS) with a low surface energy on the structure and physicochemical properties of starch/poly (butylene adipate-co-terephthalate) (PBAT) blown films. The film's appearance was not significantly changed after the addition of PDMS. Compared with the films without PDMS, the films with PDMS displayed a smoother surface. A 2% w/w PDMS addition resulted in the maximum mechanical properties (8.10 MPa of strength, 211.00% of modulus) and surface hydrophobicity (87°) of the films. By contrast, the film with 3% w/w PDMS showed the lowest light transmittance, water vapor (2.73 × 10-11 g·cm·cm2·s-1·Pa-1) and oxygen permeability (9.73 × 10-13·cm3·cm·cm-2·s-1·Pa-1), owing to the improved tightness of the matrix, which increased the zigzag path for molecules to pass through. Films with higher PDMS contents effectively extended the shelf life of packaged bananas and shiitake mushrooms, benefiting from the outstanding and appropriate barrier properties, according to principal component analysis results. Findings supported that high-content starch/PBAT films containing PDMS had potential in the preservation of fresh agricultural products.

Distribution and genotyping of hepatitis C virus (HCV) infection in Gansu province, China.

INTRODUCTION: The distribution of common subtypes of hepatitis C virus (HCV) in Gansu province were analyzed. This information provided a theoretical basis for the selection of appropriate antiviral treatment regimens. METHODOLOGY: We collected data on HCV antibody screening tests from 421,802 outpatients and inpatients at the Second Clinical Hospital of Lanzhou University from January 2018 to June 2022. Ribonucleic acid (RNA) viral load, HCV genotypes, and HCV quantification were analyzed retrospectively. The results of HCV positive detection rate, copy number, and genotype distribution were statistically analysed using SPSS 26.0. RESULTS: A total of 421,802 HCV antibody screenings were performed resulting in 4,558 positive cases (1.081%). In addition, 2,345 cases (1.302%) were positive with quantitative HCV antibodies in 180,157 outpatients and inpatients. Quantitative HCV virus RNA was further measured in 2592 outpatients and inpatients. There were 825 positive cases for HCV, with a positivity rate of 31.83%. High-sensitivity quantification of HCV-RNA was performed in 6538 patients, among which 1336 were HCV-RNA positive infections (positivity rate of 20.43%). Among the 1484 genotype tests, 4 genotypes and 10 subtypes were detected, including 4a, 1b, 2a, 2b, 3a, 3b, 6a, 6n, 1b/2a, and 2a/6a, with the majority of results from 2a (51.89%) and 1b (42.72%). CONCLUSIONS: The most prevalent genetic subtype in HCV-positive patients in Gansu was 2a, followed by 1b. In addition, 8 genotype subtypes appeared: 1a, 2b, 3a, 3b, 6a, 6n, 1b/2a and 2a/6a. Understanding the distribution of HCV genes in Gansu province is of significance for the optimization of virus treatment.

Evaluating the psychometric properties of the Hispanic Stress Inventory-2 Simplified version among a diverse sample of Latinos who smoke.

OBJECTIVE: Acculturation stress can negatively impact Latinos immigrant mental and physical health related behaviors such as smoking. It is essential to have validated and updated instruments that allow the evaluation of acculturation stress on this population. This study aims to evaluate the psychometric properties of an abbreviated version of the Hispanic Stress Inventory Version 2 (HSI2) immigration scale among Latinos who smoke. METHODS: The study consisted of a secondary data analysis from a baseline assessment of Decídetexto, a mobile health (mHealth) smoking cessation randomized clinical trial. Of 457 Latinos included in the parent study, 352 immigrants who smoke were included. Construct validity was analyzed by completing a Pearson correlation coefficient matrix. Structural validity was analyzed using an Exploratory Factor Analysis (EFA). Cronbach alpha analysis was used to estimate the internal consistency of the items constituting a factor. RESULTS: The results included an abbreviated version of the HSI2 including 52 items. From the Pearson correlation coefficient matrix with a cutoff point of 0.4, 22 of the 52 items were excluded. From the Pearson correlation coefficient matrix with a cutoff point of 0.4, 22 items were excluded. Exploratory Factor Analysis (EFA) results in six factors extracted, explaining 69.1% of the variance. According to the EFA, two items were relocated in different factors from the original scale. The HSI2 30 items scale reflected excellent reliability with a Cronbach's alpha coefficient of 0.93. The six factors reflect acceptable to excellent reliability, ranging from 0.77-0.93 across factors. The median for the HSI2 total score was 34.00 (25-45) out of a possible total score of 150. CONCLUSION: Results confirmed acceptable psychometric properties of the HSI2 simplified 30-item version and provided a reliable and shorter measure of acculturation stress for Latinos groups. Having a valid and reduced measure of acculturation stress is the first step in understanding diverse ethnic groups of Latinos that are at higher risk of presenting health risk behaviors such as smoking. The present results provided the possibility of assessing the impact of acculturation stress among adults who smoke.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta­analysis of eight short­term, randomized, double­blind, placebo­controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Solitary bone plasmacytoma: Long-term clinical outcomes in a single center.

BACKGROUND: A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of the lesion. Despite the high local control rate with radiotherapy, approximately half of patients' conditions progress to multiple myeloma (MM) within 3-5 years after diagnosis, with SBP having a worse prognosis. PATIENTS AND METHODS: We retrospectively assessed the treatment and outcomes of patients with SBP in a hospital in China from 2008 to 2021. Twenty-four patients treated over 13 years with SBP were enrolled in this retrospective study. RESULTS: The most common sites for SBP were the axial skeleton and femur. The M protein was detected in 11 patients (46 %), of which 8 (33 %) had light chains, 2 (8 %) had immunoglobulin G kappa and 1 (4 %) had immunoglobulin D kappa. Flow cytometry revealed that 5 patients (21 %) had minimal bone marrow involvement. The treatment included chemotherapy, surgery, and radiotherapy in 18 (75 %), 12 (50 %), and 9 (38 %) patients, respectively, of whom 13 (54 %) received combined treatment. Over a median follow-up period of 67.2 months, 9 patients (38 %) developed MM in a median time of 101.5 months. The 5- and 10-year progression-free survival rates were 67.3 % and 37.4 %, respectively. One patient died due to pneumonia without progression and the other died due to relapse. CONCLUSION: This study confirmed the high rate of progression of SBP to MM, indicating a need for adjunct chemotherapy for the management of SBP.