Browse Articles

Sensors pinpoint the exact time of a Yellowstone explosion

From fat to facts: Anthropometric references and centile curves for sum of skinfolds and waist-to-hip ratio in 2,507 adults

Background and aims Direct assessment of skinfold thickness and waist and hip girths provides information about body fat and its distribution, avoiding estimation errors due to predictive equations. The present study aimed to provide new centile curves for the sum of eight skinfold thicknesses (Σ8SKF) and waist-to-hip ratio (WHR) in adult population, and to identify breakpoints during adulthood. Methods The present investigation was conceived as a multicenter, cross-sectional study. Stature, body mass, eight skinfold thicknesses (i.e., triceps, biceps, subscapular, iliac crest, supraspinal, abdominal, thigh, and calf) and waist and hip girths were measured according to the International Society for the Advancement of Kinanthropometry protocol in 1,313 men and 1,194 women aged 18–65 years. Smoothed age- and sex-specific percentile curves were generated using the Lambda Mu and Sigma method. For both sexes, simple linear regressions of the dependent variable (Σ8SKF and WHR) versus the explanatory variable (age) were performed to investigate changes in the response variable’s slope and to test for potential breakpoints. Results Reference percentile curves (3rd, 10th, 25th, 50th, 75th, 90th, and 97th) for Σ8SKF and WHR were provided. In men, Σ8SKF increased by 1.0 mm/year between the ages of 21 and 59, while in women, it increased by 3.8 mm/year between the ages of 38.5 and 47. In men, WHR showed a progressive increase of 0.004/year until the age of 28.4, followed by a slower increase of 0.003/year throughout the lifespan. In women, WHR increased by 0.003/year from the age of 20–65. Conclusions Σ8SKF and WHR appear sex- and age-specific. Scientists and practitioners are provided with reference values for the adult population.

SHR-A1811, a novel anti-HER2 antibody–drug conjugate with optimal drug-to-antibody ratio, efficient tumor killing potency, and favorable safety profiles

HER2-targeting antibody–drug conjugates (ADCs), especially trastuzumab deruxtecan (T-DXd), have revolutionized the treatment landscape of HER2-expressing or mutant cancers. However, undesired adverse events are still inevitable and it is necessary to discover a HER2-directed ADC with better safety profiles. SHR-A1811 is composed of trastuzumab, a cleavable linker and a novel topoisomerase I inhibitor, SHR169265. The results indicated that SHR169265 shows better permeability, strong cytotoxicity and faster systemic clearance than DXd analog (SHR197971). The drug-to-antibody ratio (DAR) of SHR-A1811 was optimized as 6 via balancing efficacy and toxicity. SHR-A1811 showed HER2-dependent growth inhibition against various cell lines and desirable bystander killing capability. SHR-A1811 led to tumor growth inhibition or even regression in a dose-dependent manner, at least comparable as HRA18-C015 (a synthesized T-DXd) and anti-HER2-SHR169265 (DAR 8) in multiple mouse xenograft models with a range of HER2 expression levels. SHR-A1811 exhibited a good pharmacokinetics profile, outstanding stability in plasma across different species and a favorable preclinical safety profile. The highest non-severely toxic dose (HNSTD) in cynomolgus monkeys was 40 mg/kg with thymus as the main target organ. The above results suggested that SHR-A1811 is a potential best-in-class anti-HER2 ADC with a highly permeable payload, optimized DAR, great potency and better safety profiles. Currently SHR-A1811 has entered phase II and phase III clinical studies for breast cancer, gastric cancer, colorectal cancer, and NSCLC.

The complex interplay of personal and external factors in medical students’ specialty decision-making: A qualitative study

Background Medical students’ specialty decisions are shaped by a complex interaction of personal characteristics, academic experiences, social influences, and broader contextual factors. In lower-middle-income countries, where Western medical curricula are adapted to local educational and cultural contexts, little is known about how students make sense of these influences in shaping their future professional roles. This study aimed to explore how students interpret and construct their specialty choices in a newly established hybrid medical curriculum in Vietnam. Methods This qualitative study used an interpretive phenomenological approach. Semi-structured interviews were conducted with 27 medical students across all four academic years at a Vietnamese medical school. Participants were selected through purposive sampling to ensure diverse academic backgrounds and training levels. Interviews were thematically analyzed using an inductive framework to identify how students experienced and interpreted influences on their specialty decisions. Results Four interrelated themes emerged from the analysis. First, students described how personality traits shaped their emerging identity and influenced specialty preferences. Second, academic and extracurricular experiences, including clinical rotations, research, and volunteer work, were viewed as transformative encounters that clarified career direction. Third, students navigated financial hardship, family expectations, and academic pressure, often interpreting these constraints as factors in negotiating or compromising their career choices. Finally, the COVID-19 pandemic prompted moral reflection, with some students reaffirming frontline aspirations and others shifting toward specialties offering personal safety or opportunities for systemic impact. Conclusion Medical specialty choice is a reflective and identity-driven process shaped by personal dispositions, experiential learning, social pressures, and contextual disruptions. Rather than being solely determined by traits or external incentives, students engage in an evolving interpretation of who they are and what kind of doctor they wish to become. Medical education should incorporate reflective support systems to guide students through this complex process.

How do I choose a principal investigator for my next postdoc?

Diversity in knowledge search paths and breakthrough technological innovation: Evidence from new energy vehicle firms

Breakthrough technological innovations have heralded a transformative era within the automotive industry. Knowledge search diversity, as the key to acquiring the raw materials for knowledge recombination, enables firms to overcome resource constraints and accelerate the realization of breakthrough technological innovations. This paper integrates the theories of organizational search and knowledge recombination theory and draws upon the relationship between knowledge and industry to distinguish between basic knowledge search diversity and applied knowledge search diversity. It further investigates the distinct relationships between these two forms of knowledge search diversity and their respective contributions to breakthrough technological innovations. We develop research hypotheses and employ a negative binomial fixed-effects regression model to empirically test data from 280 Chinese new energy vehicle (NEV) manufacturers. The results demonstrate that: (1) knowledge search diversity exhibits an inverted U-shaped relationship with breakthrough technological innovation; (2) the inverted U-shaped relationship is steeper for basic knowledge search diversity compared to applied knowledge search diversity; (3) organizational proximity positively moderates the inverted U-shaped relationship between knowledge search diversity and breakthrough technological innovation. The findings provide practical insights into optimizing knowledge search strategies for technological convergence and accelerating the internalization of external resources to foster innovative transformation and upgrading.

Iron uptake by Escherichia coli in urinary tract infections and urosepsis

The pathogenesis of urosepsis in uncomplicated and community-acquired urinary tract infections (UTIs) caused by Escherichia coli was studied. We hypothesized that siderophores involved in iron uptake may determine bacterial adaptation to the urine and blood environment in patients with UTI, leading to urosepsis. E. coli isolates were compared from urosepsis patients (cases) and UTI (control group). The patterns of bacterial DNA fingerprints isolated from the blood and urine of patients with urosepsis were compared by PCR melting profile method to detect urosepsis and exclude nosocomial infection. Chromium Azurol S (CAS) assay and RT-qPCR were used to investigate the expression levels of siderophore genes in artificial urine and M9 supplemented with whole blood. E. coli isolates from artificial urine were proteomically analysed. The pro-inflammatory factors IL-2,4,6,8,10, IFN-gamma, TNF-alpha and CRP were quantified in the patients’ serum. PCR detected and co-occurrence of enterobactin, aerobactin and yersiniabactin was significantly more frequent in the urosepsis (P = 0.0039) and with the iha gene may represent markers of urosepsis risk. Aerobactin was dominant in urosepsis (P = 0.03), but its expression in artificial urine was twice higher than in blood (P = 0.03). When cultured in artificial urine, the expression of entC was significantly higher (P = 0.029), while the expression of iro-2, iucA and iroB were lower in strains obtained from urosepsis (P = 0.007; P = 0.030; P = 0.012; respectively) as compared to the UTI group. Ferritin-1, iron uptake system component EfeO, ferrous iron transport protein B, nitrate/nitrite response regulator protein NarL, protein HemY, ferrienterobactin receptor FepA, lipopolysaccharide export system protein LptA and 2Fe-2S ferredoxin were found by proteomic analyses in urosepsis only. A positive association of IL-6,8,10, TNF and CRP proteins with urosepsis was observed. In conclusion, risk factors for UTI-related sepsis may be related to the iron uptake system, and genetic and proteomic profiles may help identify them.

How to nudge students toward healthier snacks? Consumer neuroscience insights on multisensory nudge interventions in university vending machines

Nudge has proven effective in promoting healthier eating, especially in academic environments. However, its application in vending machines has not been extensively studied yet, with existing studies focusing on choice and overlooking the emotional and cognitive responses to these interventions. Our research explored how visual and olfactory nudges (and a combination of both) can encourage healthier choices in university vending machines, and examined the related emotional and cognitive reactions, adopting a consumer neuroscience approach. It encompassed three distinct analysis levels: behavioral (snack choice), neurophysiological (emotional and cognitive reactions assessed through skin conductance and electroencephalography), and attentional (visual attention on snacks evaluated via eye-tracking). The findings revealed that while visual and olfactory nudges, when considered individually, were associated with an increased likelihood of making healthier choices, their combined effect was not significant. Skin conductance indicated that olfactory and combined nudge interventions induced relaxation, potentially promoting healthier choices. Electroencephalography results suggested a reduced motivational approach toward snacks when both nudges were combined. Eye-tracking indicated that individuals pay heightened attention to healthy snacks when positioned at eye level, however, this can also be affected by the nudge condition. Our findings suggest that implementing visual or olfactory nudges alone may promote healthier choices in vending machines, whereas combining them may lessen their impact, and corroborate the importance of positioning target products in locations where they are readily visible to consumers. These insights enhance our understanding of the emotional, cognitive, and attentional components behind nudge interventions and offer practical strategies for promoting healthier eating habits.

Tooth discoloration caused by nanographene oxide as an irrigant and intracanal medicament in the endodontic treatment of extracted single-rooted teeth: An ex-vivo study

Tooth discoloration caused by intracanal medicaments and irrigants presents a significant aesthetic challenge in dentistry. This study aimed to investigate the discoloration effects on tooth of nanographene oxide and positively charged silver nanoparticles and compares them with other commonly used materials in endodontic treatment. A total of 108 single-rooted, single-canal anterior mandibular and maxillary premolar teeth, extracted for orthodontic or periodontal reasons, were selected and prepared. The specimens were randomly divided into seven experimental groups and two control groups, each containing 12 samples. The experimental groups included three irrigants: nanographene oxide, sodium hypochlorite, and positively charged silver nanoparticles. The four medicament groups were nanographene oxide-carboxymethyl cellulose, positively charged silver nanoparticles-carboxymethyl cellulose, calcium hydroxide, and carboxymethyl cellulose. The control groups consisted of normal saline and blood. Discoloration was assessed at five time points: before material placement (T0), immediately after placement (T1), one week later (T2), one month later (T3), and three months later (T4). Spectrophotometric analysis was used to measure discoloration, and the ∆E values were statistically analyzed using repeated measures ANOVA and Tukey’s post-hoc tests. After three months, no statistically significant difference in discoloration was observed among the irrigants (P > 0.05). However, the highest degree of discoloration was found in the silver nanoparticles group. Significant differences in ∆E values were noted between the normal saline group and both the silver nanoparticles (P = 0.001) and blood (P = 0.007) groups. Among the intracanal medicaments, a significant difference in ∆E values was observed between the carboxymethyl cellulose and calcium hydroxide groups (P = 0.005) at the final three-month examination. No significant differences were found among the other groups (P > 0.05). Nanographene oxide, used as both an irrigant and medicament, does not cause more discoloration than other commonly used materials in endodontic treatment. Therefore, it can be considered a viable alternative to traditional endodontic materials.

This tiny robot moves mini-droplets with ease

Comprehensive multi-omics analysis reveals the prognostic and immune regulatory characteristics of the PTPN family in osteosarcoma

Osteosarcoma is a highly aggressive bone tumor that primarily affects adolescents and young adults, posing significant challenges in therapeutic efficacy, prognostic assessment, and treatment strategies. This study investigates the oncogenic and immune regulatory roles of the PTPN family in osteosarcoma using a comprehensive multi-omics approach. We utilized transcriptomic data, single-cell RNA sequencing (scRNA-seq), and clinical information obtained from publicly available databases. Dimensionality reduction and clustering techniques were employed to subclassify immune cells and analyze the tumor microenvironment characteristics. We identified prognostic genes associated with the PTPN family and stratified osteosarcoma cases into distinct molecular subtypes using consensus clustering. A random forest model revealed that the PTPN family has a significant impact on prognosis and modulates key oncogenic pathways. Furthermore, we analyzed the role of the PTPN family in regulating immune cells and selected PTPN23 for experimental validation. This research not only enhances prognostic assessments in osteosarcoma but also establishes a foundation for personalized therapeutic interventions.

Stories that are out of this world: Books in brief

Effects of urbanization and land expropriation on the livelihoods of peri-urban farmers in North Wollo Zone, Ethiopia

The aim of this study was to examine the effects of urbanization and land expropriation on the livelihoods of Peri-urban farmers in North Wollo Zone, Ethiopia. Data were collected from 378 peri-urban farmers using a structured questionnaire and multistage sampling. Qualitative data were obtained through focus group discussions and key informant interviews. A binary logistic regression model was used to identify factors influencing livelihood diversification among expropriated farm households. The results revealed a significant trend of expropriation without fair compensation, stemming from the disregard of legal procedures of expropriation and compensation in the study area. On average, 33.06% of respondents were fully expropriated and evicted, while the majority (66.94%) lost only part of their agricultural land. Expropriated farmers faced numerous challenges during their livelihood diversification, including high inflation, lack of urban living skills, informal land sales at low prices, misuse of compensation, displacement, family conflicts, social disruption, and skill gaps. They also blamed that they did not get any government support in properly utilizing compensation money for livelihood diversification. The Logit model results showed that livelihood diversification is positively influenced by factors such as the household head’s education, marital status, access to alternative land, fair compensation, off-farm employment, training, social networks, and livestock assets. It is negatively affected by farming as the primary occupation, household size, and expropriated land size. The study recommends that the government should help families of expropriated household’s secure sustainable livelihoods through fair compensation and proper support.

Effect of the exposure to brominated flame retardants on hyperuricemia using interpretable machine learning algorithms based on the SHAP methodology

Background Brominated flame retardants (BFRs) are classified as important endocrine disruptors and persistent organic pollutants; nevertheless, there is no comprehensive investigation to evaluate the association between BFRs and hyperuricemia, and the available studies related to this field are exceptionally scarce. Methods For this study, we enrolled 3,812 individuals from NHANES 2005–2016, with nine different types of BFRs serving as the exposure. We conducted advanced machine learning techniques, along with regression analysis to validate our findings from diverse perspectives. Weighted logistic regression were employed to evaluate the association of BFRs for both continuous variables after logarithmic transformation and their quartile subgroups with hyperuricemia. Restricted cubic spline (RCS) analysis was conducted to identify whether a non-linear relationship exists. Subgroup analysis enabled us to explore potential interactions of research findings across different groups. Weighted quantile sum (WQS) regression was performed to assess collective mixture sum impact, along with contributions of each component. Nine machine-learning models were developed for hyperuricemia prediction, and six discrimination characteristics were applied to select the optimal model. SHapley Additive exPlanations (SHAP) was utilized to interpret the contributions of selected variables for model decision-making capacity. Results Several BFRs exhibited noticeable positive correlation with the prevalence of hyperuricemia, including PBDE28 (OR: 1.27, 95% CI: 1.05–1.54, P-value = 0.014), PBDE47 (OR: 1.19, 95% CI: 1.02–1.40, P-value = 0.032), PBDE85 (OR: 1.16, 95% CI: 1.01–1.34, P-value = 0.036), PBDE99 (OR: 1.17, 95% CI: 1.02–1.34, P-value = 0.025), and PBDE154 (OR: 1.16, 95% CI: 1.00–1.34, P-value = 0.050) after fully adjustment. The WQS analysis found that the sum effect of BFRs was positively associated with hyperuricemia, of which PBDE28 (28.70%), PBDE85 (22.10%) and PBDE47 (14.90%) were the top 3 components. XGboost exhibited superior performance across several important metrics. The SHAP analysis revealed that the PBDE85, PBDE28 and PBDE154 exhibited considerable influence, ranking after “BMI≥30”, “Race-Non-Hispanic Black” and “Hypertension-Yes”. Conclusions Combining the outcomes, our study identified PBDE28 and PBDE85 as the two major significant contributors to elevated prevalence of hyperuricemia. Other components, such as PBDE154, PBDE47, PBDE99, and PBDE100, emerged as potential pollutants. These pioneering efforts highlighted the previously underrecognized impact on this environmental and public health concern.

Rare and novel variant load threshold for KIF7, GJA1 and PDE1C genes elevates the risk of severity of congenital heart defects in Down syndrome

Individuals with Down syndrome (DS) exhibit a higher incidence of congenital heart defects (CHD). The objective of the present study was to investigate ethnicity-specific genetic variants that increase the risk of CHD in children with DS from the Indian Bengali population. We conducted whole exome sequencing of the genomes of Down syndrome children with and without CHD and subsequently tested the identified variants in a larger cohort (N = 1798). Our findings revealed two rare variants, KIF7 rs138354681 and GJA1 rs778110855, as well as one novel variant, PDE1C PP785745, present in children with DS and CHD but absent in those without CHD. In-silico analyses indicated that these variants are pathogenic. The frequencies of the heterozygous genotypes for KIF7 rs138354681, GJA1 rs778110855, and PDE1C PP785745 were recorded as 0.027, 0.016, and 0.032, respectively. Among the 31 carriers identified, 18 individuals exhibited two variants, while four were found to have three co-occurring variants. The majority of these individuals required surgical intervention for correction, in contrast to single variant carriers, of whom only three out of nine needed surgeries. A polygenic risk score analysis revealed higher score to be significantly associated with both the presence of multiple variants and the subsequent need for surgical correction. We hypothesise that the synergistic effects of multiple variants heighten the severity of CHD, particularly in cases of ventricular septal defects, thereby necessitating surgical correction. These findings significantly enhance our understanding of the unique population-specific aetiology of CHD and the basis for the severity of its clinical presentation in individuals with Down syndrome.

Alpha-1 Antitrypsin Deficiency-Associated panniculitis: A survey of lived experience

Introduction Alpha-1 Antitrypsin Deficiency (AATD)-associated panniculitis is a rare inflammatory condition characterized by painful subcutaneous plaques or nodules, often accompanied by ulceration or oily discharge. Despite its clinical and emotional burden, limited data exist on the lived experiences of individuals with this condition. Method An international online survey was conducted between April and July 2024, targeting individuals with AATD-associated panniculitis. The survey, co-designed with an affected individual and multi-disciplinary specialists, included 32 questions on demographics, diagnostic journey, life impact, and treatments. Responses were analysed using descriptive statistics and thematic analysis. Results 41 responses were included in the analysis (68% female; mean age 52.3 years). Participants reported lesions at diverse sites, affecting the lower and upper limbs, followed by the trunk, buttocks, and genitalia. 41.5% experienced both ulceration and oily discharge. 61% of participants reported being misdiagnosed which negatively affected their mental health. More than half of respondents ‘strongly agreed’ or ‘agreed’ that living with alpha-1 panniculitis had made them anxious. Access to specialist care was a major concern, with 69% finding it difficult to obtain specialist advice. Treatments varied, and augmentation therapy was identified as the subjectively the most effective. Open-ended responses revealed gaps in healthcare professionals’ awareness and highlighted the need for better mental health support and specialist access. Conclusion AATD-associated panniculitis significantly impacts physical, emotional, and social well-being. Addressing gaps in diagnosis and treatment, increasing healthcare providers awareness, and adopting multidisciplinary approaches are essential to improve individuals’ outcomes and quality of life.

Approaches and results of intersectoral actions for tuberculosis control in the world: A scoping review

Background Tuberculosis is a neglected disease with a wide global scope that overcomes public health challenges, also constituting an obstacle to social development. In the effort to control the disease, Tuberculosis Control Programs around the world have aligned their actions with the World Health Organization End TB Strategy, which emphasizes intersectorality as a fundamental component for effective disease control. Objective To map the approaches and results of intersectoral tuberculosis control actions at the global scenario. Methodology This scoping review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Joanna Briggs Institute manual, ensuring methodological rigor and transparency. The review protocol was registered in the Open Science Framework. Searches were carried out in indexed databases and in the gray literature. Data collection took place by two independent reviewers, with results stored and organized in spreadsheets. Results Three hundred and ninety-six (396) studies were identified, of which 60 were analyzed in full, resulting in the inclusion of 11 studies for the final review. It was evidenced that intersectoral articulation is fundamental in tuberculosis control, involving sectors such as health, education, social assistance and justice, to ensure adequate health care and social support, particularly for vulnerable populations. Community education and awareness played a central role in treatment adherence and reducing stigma, while resource mobilization was needed to maintain health services, especially in contexts of scarcity. Conclusion The integration of intersectoral services, involvement of non-governmental organizations and active community participation are essential elements for effective tuberculosis control. The findings reinforce the importance of addressing the social determinants of health to achieve the objectives of the End TB strategy, promoting an environment conducive to the prevention, early detection and effective treatment of the disease.

Impact of out-of-pocket expenses on children with cancer in Tanzania: A mixed-methods economic study

Background For children with cancer in low- and middle-income countries, medical and non-medical expenses are often paid through out-of-pocket (OOP) expenditures, which pose significant barriers to timely care. Our study aims to estimate the impact of OOP expenditures for cancer care for children in Tanzania through a mixed-methods approach. Methods We used an explanatory mixed-method design to evaluate the impact of OOP expenditures for children receiving cancer care at the Kilimanjaro Christian Medical Center in Tanzania based on the Three Delays Framework. Quantitative data were collected to measure OOP expenditures and to assess the risk of catastrophic health expenditure or depth of impoverishment associated. Qualitative interviews were conducted to evaluate financial barriers and facilitators to care and were analyzed using thematic content analysis. Qualitative and quantitative data were triangulated to compare themes, identify areas of agreement or dissonance, and assess for complementarity. Results Thirteen caregivers of children with cancer at KCMC formed the study cohort. Most lived in a rural setting (92%) and were farmers or livestock keepers (68%). Quantitative analysis showed that total median OOP health expenditures were $53.01 (IQR: 26.50–106.01). All families were pushed further into poverty from the OOP expenses as shown by widening poverty gaps. Qualitative interviews revealed several themes related to financial challenges for families with cancer, particularly during the time period prior to definitive care including worry about job losses and having to sell assets to reach care. Data triangulation confirmed strong agreement between qualitative and quantitative data on the impact of financial barriers on care. However, families stated higher OOP costs in qualitative interviews compared to quantitative data. Conclusions Protecting families from impoverishment by reducing OOP costs during time periods prior to receiving definitive care may be a strategic way to improve timely diagnosis and early treatment for children with cancer.

Fatty liver index and risk of type 2 diabetes of adults with normoglycemia: Insights into insulin sensitivity and beta-cell function

The fatty liver index (FLI) is a simple tool used to assess metabolic dysfunction-associated fatty liver disease (MAFLD). Previous studies have shown the utility of the FLI as an early predictor of diabetes for patients with prediabetes. We evaluated whether the FLI could predict the development of type 2 diabetes mellitus (T2DM) with normal glucose tolerance (NGT) by performing a retrospective assessment of a community-based cohort over the course of 18 years. We analyzed data of 6,083 adults with NGT available from the Korean Genome and Epidemiology Study database. Participants were stratified into the following three groups based on the FLI: low, FLI < 30; intermediate, FLI 30–59; and high, FLI ≥ 60. Cox proportional hazards regression models evaluated the T2DM risk differences. Insulin sensitivity and secretion markers were compared using multivariate linear regression and an analysis of covariance. The predictability of the FLI for T2DM was analyzed by comparing the area under the receiver-operator characteristic (ROC) curve (AUC) values from the ROC analysis. The cumulative incidence of T2DM was 31.9% for the high FLI group; however, it was 11.3% for the low FLI group (log-rank test, P < 0.0001). For individuals with NGT, a high FLI was associated with an increased T2DM risk (hazard ratio [HR], 3.42; 95% confidence interval [CI], 2.91–4.00). After adjusting for insulin sensitivity and secretion markers, FLI remained an independent predictor of T2DM (HR, 1.96, 95% CI, 1.54–2.50). The homeostasis model assessment of insulin resistance results and composite insulin sensitivity index of the high FLI group were higher than those of the other groups (P < 0.0001). However, the disposition index and insulin secretion-sensitivity index-2 of the high FLI group were lower than those of the intermediate FLI group (P = 0.027 and P = 0.011, respectively). The ROC analysis confirmed that the FLI had the highest predictive ability for T2DM (AUC, 0.654; P < 0.05) development in individuals with NGT compared to other insulin sensitivity and secretion markers. The FLI is an early predictor of T2DM that reflects underlying insulin sensitivity and β-cell function. These findings underscore the role of liver steatosis in the early T2DM pathogenesis and highlight the need for early preventive lifestyle interventions among individuals with normoglycemia and high FLI values.

Influence of capping agents on physicochemical properties and leukemic cytotoxicity of copper oxide nanoparticles biosynthesized using Caesalpinia sappan extract

The aim of this study was to investigate the effects of capping agents on the physicochemical and biological properties, particularly their leukemic cytotoxicity, of copper oxide nanoparticles (CuONPs) using a Caesalpinia sappan extract as a reducing agent. Gelatin, polyethylene glycol 400 (PEG), polysorbate 80 (P80), octyl phenol ethoxylate, sodium lauryl ether sulfate and mannitol were added as capping agents to ensure colloidal stability of the formed CuONPs. As a control, CuONPs were also synthesized using gelatin and sodium borohydride as the capping and reducing agent, respectively. The physicochemical properties of the obtained CuONPs were determined using dynamic light scattering, zeta-potential measurements, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. Their cytotoxic effects were investigated using normal human peripheral blood mononuclear cells (PBMC) and three strains of leukemic cell lines (KG1a, K562, and Molt4). The obtained CuONPs had a size range from 175–280 nm, with a reasonable size distribution between 0.2 and 0.4 and a negative zeta potential (range −30 to −35 mV) except the particles prepared using gelatin as a stabilizer which had a zeta potential of −3 mV. The CuONPs were incubated with both healthy PBMC and three types of leukemic cells to determine their IC50 values. The IC50 values of PEG-CuONPs and P80-CuONPs against healthy PBMC were 72.5 ± 5.8 and 85.0 ± 3.1 µg/mL, respectively, while that against the three strains of leukemic cells were in the range of 26–29 and 28–41 µg/mL, respectively. The results clearly demonstrate that the biosynthesized CuONPs using PEG and P80 as a capping agent exhibited the highest selectivity index defined as IC50 of the particles for PBMC/IC50 for leukemic cells. Therefore, these CuONPs are promising candidates for preclinical in vivo for leukemic treatments.