RESUMEN

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Asunto(s)

RESUMEN

Accurate and objective estimation of the postmortem interval (PMI) is crucial in forensic practice. This study aimed to infer PMI through equations based on the relationship between PMI and metabolomics biomarkers.Rats were subjected to models representing various temperatures and causes of death, with blood collected at different intervals. Untargeted gas chromatographymass spectrometry metabolomics detection methods were developed, and candidate biomarkers were chosen as co-differentially expressed metabolites in four models. A targeted method was then developed for quantitatively determining candidate biomarkers. Animal tests and human cadaver samples with clearly documented causes of death and time were used to verify the reliability of the regression equation.Results: Unique differential metabolites for CO poisoning deaths included 2,3-butanediol, hypoxanthine, and dehydrated hexanol, while those for mechanical asphyxia deaths comprised propylamine, 1,3-propylene glycol, phosphoric acid, and sorbitol. Pyruvate, glycerol and isoleucine were identified as candidate biomarkers. Human case results demonstrated the method's potential (error rate < 20 %). The findings of this study may offer reference points for estimating PMI and causes of death in forensic practice.

Asunto(s)

RESUMEN

Dental caries is associated with microbial dysbiosis caused by the excessive proliferation of Streptococcus mutans in dental biofilms, where oxidative stress serves as the major stressor to microbial communities. The adaptability of S. mutans to oxidative stress is a prerequisite for its proliferation and even for exerting its virulence. Protein acetylation is a reversible and conserved regulatory mechanism enabling bacteria to rapidly respond to external environmental stressors. However, the functions of protein acetylation in regulating oxidative stress adaptability of S. mutans are still unknown. Here, we unveil the impact of acetyltransferase ActA-mediated acetylation on regulating the oxidative stress response of S. mutans. actA overexpression increased the sensitivity of S. mutans to hydrogen peroxide and diminished its competitive ability against Streptococcus sanguinis. In contrast, actA deletion enhanced oxidative stress tolerance and competitiveness of S. mutans. The mass spectrometric analysis identified pyruvate kinase (PykF) as a substrate of ActA, with its acetylation impairing its enzymatic activity and reducing pyruvate production. Supplementation with exogenous pyruvate mitigated oxidative stress sensitivity and restored competitiveness in multi-species biofilms. In vitro acetylation analysis further confirmed that ActA directly acetylates PykF, negatively affecting its enzymatic activity. Moreover, 18 potential lysine-acetylated sites on PykF were identified in vitro, which account for 75% of lysine-acetylated sites detected in vivo. Taken together, our study elucidates a novel regulatory mechanism of ActA-mediated acetylation of PykF in modulating oxidative stress adaptability of S. mutans by influencing pyruvate production, providing insights into the importance of protein acetylation in microbial environmental adaptability and interspecies interactions within dental biofilms. IMPORTANCE: Dental caries poses a significant challenge to global oral health, driven by microbial dysbiosis within dental biofilms. The pathogenicity of Streptococcus mutans, a major cariogenic bacterium, is closely linked to its ability to adapt to changing environments and cellular stresses. Our investigation into the protein acetylation mechanisms, particularly through the acetyltransferase ActA, reveals a critical pathway by which S. mutans modulates its adaptability to oxidative stress, the dominant stressor within dental biofilms. By elucidating how ActA affects the oxidative stress adaptability and competitiveness of S. mutans through the regulatory axis of ActA-PykF-pyruvate, our findings provide insights into the dynamic interplay between cariogenic and commensal bacteria within dental biofilms. This work emphasizes the significance of protein acetylation in bacterial stress response and competitiveness, opening avenues for the development of novel strategies to maintain oral microbial balance within dental biofilms.

RESUMEN

Dental caries, as a biofilm-related disease, is closely linked to dysbiosis in microbial ecology within dental biofilms. Beyond its impact on oral health, bacteria within the oral cavity pose systemic health risks by potentially entering the bloodstream, thereby increasing susceptibility to bacterial endocarditis, among other related diseases. Streptococcus mutans, a principal cariogenic bacterium, possesses virulence factors crucial to the pathogenesis of dental caries. Its ability to adhere to tooth surfaces, produce glucans for biofilm formation, and metabolize sugars into lactic acid contributes to enamel demineralization and the initiation of carious lesions. Its aciduricity and ability to produce bacteriocins enable a competitive advantage, allowing it to thrive in acidic environments and dominate in changing oral microenvironments. In contrast, commensal streptococci, such as Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, act as primary colonizers and compete with S. mutans for adherence sites and nutrients during biofilm formation. This competition involves the production of alkali, peroxides, and antibacterial substances, thereby inhibiting S. mutans growth and maintaining microbial balance. This dynamic interaction influences the balance of oral microbiota, with disruptions leading to shifts in microbial composition that are marked by rapid increases in S. mutans abundance, contributing to the onset of dental caries. Thus, understanding the dynamic interactions between commensal and pathogenic bacteria in oral microecology is important for developing effective strategies to promote oral health and prevent dental caries. This review highlights the roles and competitive interactions of commensal bacteria and S. mutans in oral microecology, emphasizing the importance of maintaining oral microbial balance for health, and discusses the pathological implications of perturbations in this balance.

RESUMEN

The continuous pursuit of novel two-dimensional (2D) materials with intriguing properties has been a driving force in advancing various scientific and technological frontiers. Here, based on a wide range of first-principles calculations, we predicted the existence of a novel family of 2D transition-metal oxides, the Ti3O MOenes (MXene-like 2D transition oxides), and determined its distinctive electronic and topological properties. A pair of 2D antiferromagnetic (AFM) Dirac points precisely located at the Fermi level in the absence of spin-orbit coupling (SOC) is observed in the 1T-Ti3O monolayer. Moreover, upon halogenation on a bare monolayer, 1T-Ti3OCl3 and 1T-Ti3OBr3 monolayers display the quantum spin Hall (QSH) effect with nontrivial helical edge states within the gapless bulk states. Specifically, single layer 1T-Ti3OF3 behaves as an indirect semiconductor with a gap of 0.81 eV, exhibiting a strong light-harvesting capability. The indirect-gap feature can be switched to a direct one by only exerting a small tensile strain of 1.5%. These findings broaden emerging phenomena in a rich family of MOenes, suggesting a novel platform for the development of next-generation nanodevices.

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: XBJ injection is approved by the China Food and Drug Administration for the adjunctive treatment of sepsis, and it is derived from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It consists of five Chinese herbal extracts: Carthamus tinctorius, Paeonia lactiflora, Salvia miltiorrhiza, Conioselinum anthriscoides 'Chuanxiong' and Angelica sinensis. AIM OF THE STUDY: The purpose of this study was to explore the relationship between ferroptosis and acute septic lung injury, and to evaluate the improvement effect of XBJ injection on acute lung injury in sepsis. MATERIALS AND METHODS: Acute lung injury was induced in rats by cecum ligation and puncture, and these rats were treated with XBJ injection. Oxidative stress and inflammation levels were assessed in serum and lung tissue, and tissue samples were collected for histological and protein analyses. To illustrate the mechanism of the improvement effect of XBJ on acute lung injury in sepsis, serum lipidomics was carried out to investigate whether XBJ prevents oxidative stress-induced lipid metabolism disorders. Furthermore, protein expression of ferroptosis-related genes was also examined. RESULTS: XBJ was shown to be effective in alleviating sepsis-induced ALI. XBJ also improves sepsis-induced acute lung injury by reducing lipid peroxidation and inflammation and modulating ferroptosis pathways. Specifically, compared with the sham group, XBJ downregulated the levels of Fe2+, MDA and GSSG, and reversed the decrease in the levels of GSH and GSH/GSSH in lung tissue. Metabolic pathways such as glycerophospholipid metabolism, phospholipid metabolism, and lipid metabolism associated with ferroptosis were obtained by lipidomic analysis of differential lipid metabolite enrichment, suggesting that ferroptosis occurs in septic rats, and that XBJ inhibits ferroptosis and thereby improves sepsis-induced ALI. Furthermore, XBJ optimises iron metabolism and lipid oxide metabolism by regulating the expression of a series of proteins that are closely related to ferroptosis, such as GPX4, ACSL4, x-CT, and FTH1. CONCLUSIONS: Our findings, initially, indicated that XBJ ameliorates sepsis-induced ALI by reducing oxidative stress and ferroptosis, revealing a previously unrecognised mechanism by which XBJ ameliorates sepsis-induced ALI.

RESUMEN

AIMS: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-ß test. METHODS: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-ß test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory. RESULTS: The median (25 %, 75 % quartile) of TIRCGM and TIRSMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIRCGM, the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIRSMBG, the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIRCGM and TIRSBMG) and LnDI30 and LnDI120 levels (p = 0.000). CONCLUSIONS: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-ß. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-ß. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control.

Asunto(s)

RESUMEN

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial. METHODS: Patients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation. RESULTS: A total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results. CONCLUSIONS: TBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions.

RESUMEN

Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness. We report a 55-year-old hypertensive patient with unknown renal function who got AKI following multiple wasp stings. His renal function had not improved after continuous hemodialysis and plasma exchange; therefore, a kidney biopsy was performed. The pathology revealed that in addition to ATN, his kidney's distinguishing feature was a mix of chronic interstitial renal disease and chronic glomerulosclerosis. We think that his current renal pathological results were caused by hypertension in addition to wasp venom.

RESUMEN

Background: Outside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit. Methods: Data from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight. Results: The cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p < 0.05). In longitudinal analyses, the EPR eating behavior in the first visit for GDM predicted lower levels of anxiety and depression in the second GDM visit, whereas the RHSC eating behavior in the first visit for GDM was associated with lower FPG in the second GDM visit (all p < 0.01). Conclusion: These results suggest that practicing intuitive eating may be beneficial and that higher intuitive eating adherence can lead to lower levels of anxiety and depression and more ideal gestational weight and blood glucose values.

RESUMEN

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

RESUMEN

Meibomian gland dysfunction (MGD) is increasingly recognized as a critical contributor to evaporative dry eye, significantly impacting visual quality. With a global prevalence estimated at 35.8 %, it presents substantial challenges for clinicians. Conventional manual evaluation techniques for MGD face limitations characterized by inefficiencies, high subjectivity, limited big data processing capabilities, and a dearth of quantitative analytical tools. With rapidly advancing artificial intelligence (AI) techniques revolutionizing ophthalmology, studies are now leveraging sophisticated AI methodologies--including computer vision, unsupervised learning, and supervised learning--to facilitate comprehensive analyses of meibomian gland (MG) evaluations. These evaluations employ various techniques, including slit lamp examination, infrared imaging, confocal microscopy, and optical coherence tomography. This paradigm shift promises enhanced accuracy and consistency in disease evaluation and severity classification. While AI has achieved preliminary strides in meibomian gland evaluation, ongoing advancements in system development and clinical validation are imperative. We review the evolution of MG evaluation, juxtapose AI-driven methods with traditional approaches, elucidate the specific roles of diverse AI technologies, and explore their practical applications using various evaluation techniques. Moreover, we delve into critical considerations for the clinical deployment of AI technologies and envisages future prospects, providing novel insights into MG evaluation and fostering technological and clinical progress in this arena.

Asunto(s)

RESUMEN

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly-2-acrylamide-2-methylpropanesulfonic acid sodium salt-grafted aminofullerene, is developed to restore the cartilage lubrication system using an "In-Out" strategy. The "Out" aspect involves reducing friction through a combination of hydration lubrication and ball-bearing lubrication. Simultaneously, the "In" aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions.

RESUMEN

BACKGROUND: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB. OBJECTIVE: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB. METHODS: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice. RESULTS: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice. CONCLUSION: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.

Asunto(s)

RESUMEN

Importance: Few studies have directly and objectively measured the individual and combined effects of multifaceted hand hygiene education programs. Objective: To evaluate the individual and combined immediate effects of an instructional video and hand scan images on handwashing quality, decontamination, and knowledge improvement. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in June to July 2023 among first-year nursing students at a university in Hong Kong. The study used an intention-to-treat analysis. Intervention: Hand hygiene education sessions featuring an instructional video, hand scan images, or both. Main Outcomes and Measures: The primary outcome was the change in residue from fluorescent lotion remaining on participants' hands after handwashing before and after the intervention. The secondary outcomes included handwashing quality and knowledge of hand hygiene. Results: A total of 270 of 280 students (mean [SD] age, 19 [1] years; 182 [67.4%] female) participated in the trial (96.4% participation rate). Participants were randomized to a control group (66 participants), hand scan image group (68 participants), instructional video group (67 participants), and hand scan image with instructional video group (69 participants). All intervention groups had greater reductions in residue after the intervention compared with the control group, although none reached statistical significance (hand scan image group: 3.9 [95% CI, 2.0-5.8] percentage points; instructional video group: 4.8 [95% CI, 2.9-6.7] percentage points; hand scan image with instructional video: 3.5 [95% CI, 1.6-5.4] percentage points; control group: 3.2 [95% CI, 1.3-5.2] percentage points). The instructional video group showed a significant improvement in their handwashing performance, with a higher percentage of participants correctly performing all 7 steps compared with the control group (22.4% [95% CI, 13.1% to 31.6%] vs 1.5% [-7.9% to 10.9%]; P < .001). Hand scan images revealed that wrists, fingertips, and finger webs were the most commonly ignored areas in handwashing. Conclusions and Relevance: In this cluster randomized clinical trial of an education program for hand hygiene, a handwashing instructional video and hand scan images did not enhance the level of decontamination. The intervention group had improved handwashing techniques compared with the control group, a secondary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT05872581.

Asunto(s)

RESUMEN

Introduction: Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures. Methods: The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran's Q test, and weighted median were employed. Results: At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable. Discussion: The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

RESUMEN

Background: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer. Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia. Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China's middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women. Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China's middle-aged and elderly male population without cancer.

RESUMEN

The practical application of the Fe-catalyzed peracetic acid (PAA) processes is seriously restricted due to the need for narrow pH working range and poor anti-interference capacity. This study demonstrates that protocatechuic acid (PCA), a natural and eco-environmental phenolic acid, significantly enhanced the removal of sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions (6.0-8.0) by complexing Fe(III). With sulfamethoxazole (SMX) as the model contaminant, the pseudo-first-order rate constant of SMX elimination in PCA/Fe(III)/PAA process was 63.5 times higher than that in Fe(III)/PAA process at pH 7.0, surpassing most of the previously reported strategies-enhanced Fe-catalyzed PAA processes (i.e., picolinic acid and hydroxylamine etc.). Excluding the primary contribution of reactive species commonly found in Fe-catalyzed PAA processes (e.g., •OH, R-O•, Fe(IV)/Fe(V) and 1O2) to SMX removal, the Fe(III)-peroxy complex intermediate (CH3C(O)OO-Fe(III)-PCA) was proposed as the primary reactive species in PCA/Fe(III)/PAA process. DFT theoretical calculations indicate that CH3C(O)OO-Fe(III)-PCA exhibited stronger oxidation potential than CH3C(O)OO-Fe(III), thereby enhancing SMX removal. Four potential removal pathways of SMX were proposed and the toxicity of reaction solution decreased with the removal of SMX. Furthermore, PCA/Fe(III)/PAA process exhibited strong anti-interference capacity to common natural anions (HCO3-, Cl-and NO3-) and humic acid. More importantly, the PCA/Fe(III)/PAA process demonstrated high efficiency for SMX elimination in actual samples, even at a trace Fe(III) dosage (i.e., 5 µM). Overall, this study provided a highly-efficient and eco-environmental strategy to remove sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions and to strengthen its anti-interference capacity, underscoring its potential application in water treatment.

Asunto(s)

RESUMEN

Indirect pulp therapy (IPT) is a common conservative treatment for deep dental caries. However, the potential risk factors for the prognosis of IPT have not been well studied. This study retrospectively investigated the success rate of IPT in treating primary molars with deep caries and the factors potentially affecting the two-year success rate. A total of 303 primary molars in 202 children (106 boys and 96 girls) were included in this study. These primary molars were identified as having deep caries by clinical and radiographic examinations and were treated with IPT. The factors potentially affecting the IPT success rate were analyzed after two years of follow-up. The results indicated that the two-year IPT success rate was 86% (262/303). The success rate of primary molars with and without stainless steel crowns was 96% (120/125) and 80% (142/178), respectively. Primary molars treated with stainless steel crowns showed a significantly lower risk of failure (hazard ratio (HR) = 0.18, 95% confidence interval (CI): (0.10, 0.34), p = 0.01). There were no significant differences in other factors, including gender (male vs. female), age (preschool vs. school age), cooperation level (Frankl 2 vs. 3 or 4 scales), arch type (maxillary vs. mandibular), tooth type (first vs. second primary molar), or pulp capping material (calcium hydroxide vs. glass ionomer cement). IPT is an effective, conservative treatment modality for primary molars with deep caries. Stainless steel crowns could significantly improve the IPT success rate.

Asunto(s)

RESUMEN

BACKGROUND: Microcystin-leucine-arginine (MC-LR) produced by various cyanobacteria during harmful algal bloom poses serious threats to drinking water safety and human health. Conventional chromatography-based detection methods require expensive instruments and complicated sample pretreatment, limiting their application for on-site detection. Colorimetric aptasensors are simple and rapid, and are amenable to fast detection. However, they provide only one output signal, resulting in poor sensitivity and accuracy. Dual-channel ratiometric colorimetric method based on the peroxidase-like activity of nanozyme can achieve self-calibration by recording two reverse signals, providing significantly enhanced sensitivity and accuracy. RESULTS: CeO2 nanocages (CeO2 NCs) with tetra-enzyme mimetic activities (oxidase-, peroxidase-, catalase- and superoxide dismutase-like activities) were facilely synthesized using zeolitic imidazolate framework-67 (ZIF-67) as sacrificial template. The peroxidase-like activity of CeO2 NCs can be regulated by DNA, and it showed opposite response to two chromogenic substrates (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB)), which was mainly attributed to the changed affinity. On the basis of MC-LR aptamer-tunable peroxidase-like activity of CeO2 NCs in TMB and ABTS channel, a dual-channel ratiometric colorimetric aptasensor was constructed for detection of MC-LR. Compared with conventional single-signal colorimetric assays, the proposed method showed lower limit of detection (0.66 pg mL-1) and significantly enhanced sensitivity. Moreover, the practicability of the ratiometric colorimetric assay was demonstrated by detecting MC-LR in real water samples, and satisfactory recoveries (94.9-101.9 %) and low relative standard deviations (1.6-6.3 %) were obtained. SIGNIFICANCE: This work presents a nanozyme-based ratiometric colorimetric aptasensor for MC-LR detection by recording the reverse responses of two chromogenic reactions. Benefiting from the self-calibration function, the method can achieve higher sensitivity and accuracy. The short detection time and practical application in real water samples show great potential for environmental monitoring.

Asunto(s)