Genome-wide association study identifies genetic risk loci for adiposity in a Taiwanese population.

Overweight and obese are risk factors for various diseases. In Taiwan, the combined prevalence of overweight and obesity has increased dramatically. Here, we conducted a genome-wide association study (GWAS) on four adiposity traits, including body-mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-hip ratio (WHR), using the data for more than 21,000 subjects in Taiwan Biobank. Associations were evaluated between 6,546,460 single-nucleotide polymorphisms (SNPs) and adiposity traits, yielding 13 genome-wide significant (GWS) adiposity-associated trait-loci pairs. A known gene, FTO, as well as two BF%-associated loci (GNPDA2-GABRG1 [4p12] and RNU6-2-PIAS1 [15q23]) were identified as pleiotropic effects. Moreover, RALGAPA1 was found as a specific genetic predisposing factor to high BMI in a Taiwanese population. Compared to other populations, a slightly lower heritability of the four adiposity traits was found in our cohort. Surprisingly, we uncovered the importance of neural pathways that might influence BF%, WC and WHR in the Taiwanese (East Asian) population. Additionally, a moderate genetic correlation between the WHR and BMI (γg = 0.52; p = 2.37×10-9) was detected, suggesting different genetic determinants exist for abdominal adiposity and overall adiposity. In conclusion, the obesity-related genetic loci identified here provide new insights into the genetic underpinnings of adiposity in the Taiwanese population.

Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status.

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (ß: -0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (ß: -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (ß: -0.81, 95%CI: -1.43, -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (ß: -1.70, 95% CI: -3.06, -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Identification and prediction model of placenta-brain axis genes associated with neurodevelopmental delay in moderate and late preterm children.

BACKGROUND: Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. METHODS: The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. RESULTS: The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. CONCLUSIONS: These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age.

BACKGROUND: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. METHODS: This study is a population-based case-control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package "mediation". RESULTS: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01-0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. CONCLUSION: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Relationships of prenatal organophosphate ester exposure with pregnancy and birth outcomes: A systematic scoping review of epidemiological studies.

Exposure to organophosphate esters (OPEs) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes. However, relevant investigations are scarce, and the findings are inconsistent. We aimed to conduct a scoping review to provide an overview of these associations. Electronic databases, including MEDLINE (through PubMed), Web of Science, and CNKI (China National Knowledge Infrastructure), were searched from inception to March 2022 and updated in July 2022. A total of 8 studies (1860 participants) were included. Limited evidence indicates that OPE exposure during pregnancy may be negatively associated with both maternal and neonatal triiodothyronine and tetraiodothyronine concentrations but positively associated with thyroid-stimulating hormone concentrations. OPE exposure during pregnancy may be associated with lower insulin concentrations. OPE exposure during pregnancy was associated with gestational age in a sex-specific manner. Intrauterine OPE exposure might increase the risk of preterm birth in female infants but decrease the risk of preterm birth in male infants. Prenatal OPE exposure might be associated with an increased risk of low birth weight. The current scoping review suggests that OPE exposure during pregnancy may disturb pregnancy and birth health, including adverse thyroid function and birth size. Because of the limited evidence obtained for most associations, additional studies followed by a traditional systematic review are needed to confirm these findings.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.

Preconception exposure to environmental antibiotics among childbearing couples in Anhui and health risk assessment: A multicenter population-based representative study.

Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.

Lifestyle behaviors and mental health during the coronavirus disease 2019 pandemic among college students: a web-based study.

BACKGROUND: After emerging in China, the novel coronavirus disease 2019 (COVID-19) quickly spread to all parts of the country and became a global public health emergency. The Chinese government immediately took a series of protective and quarantine measures to prevent the spread of the virus, and these measures may have negative effects on behavior and psychological health. This study aimed to examine the associations between factors related to COVID-19 measures and mental health symptoms among Chinese college students in different pandemic areas. METHODS: An online survey was administered to 14,789 college students from February 4 to 12, 2020. After excluding the participants who did not complete the questionnaire, the quality of the questionnaire was checked. Finally, the sample included 11,787 college students from 16 cities and 21 universities in China. The areas included the city of Wuhan (Area 1), the neighboring province of Hubei (Area 2), first-tier cities (Beijing, Shanghai, and Guangzhou [Area 3]), and other provinces (Area 4). RESULTS: The average age of the participants was 20.51 ± 1.88 years. One-third of the participants were men. In total, 25.9 and 17.8% reported depression and anxiety, respectively. We also explored COVID-19-related factors, such as infection risk, perceived resistance to COVID-19 (or susceptibility to COVID-19 infection), perceived physical symptoms, family or friends, direct or indirect contact with confirmed cases, and having sought psychological counseling, which were significantly associated with anxiety and depression symptoms. Higher screen time, lower physical activity, higher soda and tea beverages (also called sugar sweetened beverages intake), use of alternative medicines or food supplements (including Chinese herbal medicines and vitamins), and decreased meal frequency were all correlated with higher depression and anxiety symptoms (depression: χ2 = 25.57 and anxiety: χ2 = 39.42). Coping with COVID-19 partially mediated the associations between some related lifestyle behaviors, anxiety, and depression. The conditional process model analysis results supported our hypotheses that lifestyle health behaviors and coping style were both predictors of anxiety and depression symptoms, and their direct and indirect effects were moderated by sex. CONCLUSIONS: Compared with the city of Wuhan, other epidemic areas had a lower risk of mental health problems. Lifestyle health behaviors and coping styles alleviated mental health symptoms. COVID-19-related social stressors were positively associated with mental health symptoms.

Prenatal single and combined exposure to phthalates associated with girls' BMI trajectory in the first six years.

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma'anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls' body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls' body mass index (BMI) trajectory. Compared to the "lowest trajectory" class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014-4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022-5.338) during pregnancy were associated with an increased probability of being in the "highest trajectory" class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002-3.522) was associated with an increased probability of being in the "moderate trajectory" class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094-2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367-6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335-4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334-5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239-4.792) was associated with an increased probability of being in the "highest trajectory" class. However, the mixture of phthalates was not significantly related to the girl's BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls' high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls' high BMI trajectory.

Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy.

The recent outbreak of coronavirus disease 2019 (COVID-19) by SARS-CoV-2 has led to uptodate 24.3 M cases and 0.8 M deaths. It is thus in urgent need to rationalize potential therapeutic targets against the progression of diseases. An effective, feasible way is to use the pre-existing ΔORF6 mutant of SARS-CoV as a surrogate for SARS-CoV-2, since both lack the moiety responsible for interferon antagonistic effects. By analyzing temporal profiles of upregulated genes in ΔORF6-infected Calu-3 cells, we prioritized 55 genes and 238 ligands to reposition currently available medications for COVID-19 therapy. Eight of them are already in clinical trials, including dexamethasone, ritonavir, baricitinib, tofacitinib, naproxen, budesonide, ciclesonide and formoterol. We also pinpointed 16 drug groups from the Anatomical Therapeutic Chemical classification system, with the potential to mitigate symptoms of SARS-CoV-2 infection and thus to be repositioned for COVID-19 therapy.

Early childhood screen time as a predictor of emotional and behavioral problems in children at 4 years: a birth cohort study in China.

BACKGROUND: Previous studies have suggested that screen time (ST) has a negative effect on children's emotional and behavioral health, but there are few longitudinal studies that have been conducted with infants and toddlers. This study sought to examine the effect of ST in early childhood on emotional and behavioral problems in children aged 4 years, based on a birth cohort study in China. METHODS: A total of 2492 children aged 4 years were enrolled in this study. The parents and guardians of each child completed a questionnaire that included items eliciting information on children's birth information, socio-demographic information at baseline, and ST at each follow-up. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) at 4 years of age. Multivariate logistic analysis was used to explore the effects of ST on emotional and behavioral problems. RESULTS: The percentages of children with ST > 0 h/day at age 0.5 years, ST > 2 h/day at age 2.5 years, and ST > 2 h/day at age 4 years were 45.7, 55.5, and 34.5% respectively. The prevalence of emotional and behavioral problems was 10.8%. ST at 6 months was a risk factor for emotional symptoms and hyperactivity at the age of 4 years. ST at age 2.5 years was a risk factor for hyperactivity at the age of 4 years. However, ST at age 4 years was a risk factor for total difficulties, conduct problems, peer problems, hyperactivity, and prosocial behavior. CONCLUSIONS: Higher ST exposure at early childhood is associated with later emotional and behavioral problems. In particular, sustained high ST exposure is a risk factor for behavioral problems. These findings suggested the importance of controlling ST to prevent the occurrence of emotional and behavioral problems in the early years.

Stress Distributions and Micromovement of Fragment Bone of Pilon Fracture Treated With External Fixator: A Finite Element Analysis.

Osteoporosis and osteoarthritis are common pathological problems of the human bone tissue. There are some cases of pilon fractures associated with these 2 pathological conditions. In terms of treatment, for a normal and healthy bone with pilon fracture, the use of the Delta external fixator is a favorable option because it can allow early mobilization for patients and provide stability for the healing process. However, the stability of the external fixator differs when there is low bone stiffness, which has not been previously investigated. Therefore, this study was conducted to determine the stability of the external fixator to treat pilon fracture associated with osteoporosis and osteoarthritis, particularly to differentiate the stress distribution and micromovement of fracture fragment. Three-dimensional finite element models of the ankle and foot bones were reconstructed based on the computed tomography datasets. The bones consisted of 5 metatarsal, 3 cuneiform, and 1 each of cuboid, navicular, calcaneus, talus, fibula, and tibia bones. They were assigned with linear isotropic behavior. The ankle joint consisted of ligament and cartilage, and they were assigned with the use of linear links and the Mooney-Rivlin model, respectively. During simulation of the gait cycle, 70 N and 350 N were applied axially to the tibia bone to represent the swing and stance phases, respectively. The metatarsal and calcaneus bones were fixed to prevent any movement of the rigid body. The study found that the greatest von Mises stress value was observed at the pin-bone interface for the osteoporosis (108 MPa) model, followed by the osteoarthritis (87 MPa) and normal (44 MPa) models, during the stance phase. For micromovement, the osteoporosis model had the largest value at 0.26 mm, followed by the osteoarthritis (0.09 mm) and normal (0.03 mm) models. In conclusion, the greatest magnitudes of stress and micromovement were observed for the osteoporosis bone and extra care should be taken to treat pilon fracture associated with this pathological condition.

Polyoxometalates-Based Metal-Organic Frameworks Made by Electrodeposition and Carbonization Methods as Cathodes and Anodes for Asymmetric Supercapacitors.

Hybrid materials have obtained well-deserved attention for energy storage devices, because they show high capacitances and high energy densities induced by the synergistic effect between complementary components. Polyoxometalate-based metal-organic frameworks (POMOFs) possess the abundant redox-active sites and ordered structures of polyoxometalates (POMs) and metal-organic frameworks (MOFs), respectively. Here, an asymmetric supercapacitor (ASC) NENU-5/PPy/60//FeMo/C was fabricated in which both its electrodes are prepared from POMOF precursors. A typical POMOF material, NENU-5, was first connected with polypyrrole (PPy) through electrodeposition to form the cathode material NENU-5/PPy. Another representative POMOFs material, PMo12 @MIL-100, was carbonized to obtain the anode material FeMo/C. Cathode NENU-5/PPy exhibited an extraordinary capacitance of 508.62 F g-1 (areal capacitance: 2034.51 mF cm-2 ). In addition, anode FeMo/C shows excellent cyclic stability attributed to its unique structure. Finally, benefiting from the outstanding capacitances and structural merits of the anode and cathode, assembled asymmetric supercapacitor NENU-5/PPy/60//FeMo/C achieves an energy density of 1.12 mWh cm-3 at a power density output of 27.78 mW cm-3 , as well as a notable life of 10 000 cycles with an capacity retention of 80.62 %. Thus, the unique ASC is strongly competitive in high capacitance, long cycle life, and high energy-required energy storage devices.

Kinetically-Driven Phase Transformation during Lithiation in Copper Sulfide Nanoflakes.

Two-dimensional (2D) transition metal chalcogenides have been widely studied and utilized as electrode materials for lithium ion batteries due to their unique layered structures to accommodate reversible lithium insertion. Real-time observation and mechanistic understanding of the phase transformations during lithiation of these materials are critically important for improving battery performance by controlling structures and reaction pathways. Here, we use in situ transmission electron microscopy methods to study the structural, morphological, and chemical evolutions in individual copper sulfide (CuS) nanoflakes during lithiation. We report a highly kinetically driven phase transformation in which lithium ions rapidly intercalate into the 2D van der Waals-stacked interlayers in the initial stage, and further lithiation induces the Cu extrusion via a displacement reaction mechanism that is different from the typical conversion reactions. Density functional theory calculations have confirmed both the thermodynamically favored and the kinetically driven reaction pathways. Our findings elucidate the reaction pathways of the Li/CuS system under nonequilibrium conditions and provide valuable insight into the atomistic lithiation mechanisms of transition metal sulfides in general.

Perineural dexamethasone does not enhance the analgesic efficacy of ultrasound-guided subcostal transversus abdominis plane block during laparoscopic cholecystectomy.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efficacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the analgesic efficiency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who underwent laparoscopic cholecystectomy. METHODS: Sixty patients who underwent laparoscopic cholecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the first-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at specific intervals. RESULTS: Compared to group I, the first-time requirement of rescue-analgesia in groups II and III was significantly delayed (403.0+/-230.9, 436.0+/-225.3 vs 152.3+/-124.7, P<0.01). Compared with those in group I, patients in groups II and III were associated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no significant difference in the variables mentioned above between groups II and III (P>0.05). CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efficacy for the patients undergoing laparoscopic cholecystectomy.

Medical image visual appearance improvement using bihistogram Bezier curve contrast enhancement: data from the Osteoarthritis Initiative.

Well-defined image can assist user to identify region of interest during segmentation. However, complex medical image is usually characterized by poor tissue contrast and low background luminance. The contrast improvement can lift image visual quality, but the fundamental contrast enhancement methods often overlook the sudden jump problem. In this work, the proposed bihistogram Bezier curve contrast enhancement introduces the concept of "adequate contrast enhancement" to overcome sudden jump problem in knee magnetic resonance image. Since every image produces its own intensity distribution, the adequate contrast enhancement checks on the image's maximum intensity distortion and uses intensity discrepancy reduction to generate Bezier transform curve. The proposed method improves tissue contrast and preserves pertinent knee features without compromising natural image appearance. Besides, statistical results from Fisher's Least Significant Difference test and the Duncan test have consistently indicated that the proposed method outperforms fundamental contrast enhancement methods to exalt image visual quality. As the study is limited to relatively small image database, future works will include a larger dataset with osteoarthritic images to assess the clinical effectiveness of the proposed method to facilitate the image inspection.

Single-cell RNA sequencing reveals S100a9hi macrophages promote the transition from acute inflammation to fibrotic remodeling after myocardial ischemia‒reperfusion.

Rationale: The transition from acute inflammation to fibrosis following myocardial ischemia‒reperfusion (MIR) significantly affects prognosis. Macrophages play a pivotal role in inflammatory damage and repair after MIR. However, the heterogeneity and transformation mechanisms of macrophages during this transition are not well understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine monocyte-derived macrophages after MIR to investigate macrophage subtypes and their roles in the MIR process. S100a9-/- mice were used to establish MIR model to clarify the mechanism of alleviating inflammation and fibrosis after MIR. Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion (MD) in mice subjected to MIR were performed to further examine the role of S100a9hi macrophages in MIR. Results: We identified a unique subtype of S100a9hi macrophages that originate from monocytes and are involved in acute inflammation and fibrosis. These S100a9hi macrophages infiltrate the heart as early as 2 h post-reperfusion and activate the Myd88/NFκB/NLRP3 signaling pathway, amplifying inflammatory responses. As the tissue environment shifts from proinflammatory to reparative, S100a9 activates transforming growth factor-ß (Tgf-ß)/p-smad3 signaling. This activation not only induces the transformation of myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific inhibitor could effectively mitigate acute inflammatory damage and halt the progression of fibrosis, including MMT. Conclusion: S100a9hi macrophages are a promising therapeutic target for managing the transition from inflammation to fibrosis after MIR.

Unilateral external fixator and its biomechanical effects in treating different types of femoral fracture: A finite element study with experimental validated model.

Previous works had successfully demonstrated the clinical effectiveness of unilateral external fixator in treating various types of fracture, ranging from the simple type, such as oblique and transverse fractures, to complex fractures. However, literature that investigated its biomechanical analyses to further justify its efficacy is limited. Therefore, this paper aimed to analyse the stability of unilateral external fixator for treating different types of fracture, including the simple oblique, AO32C3 comminuted, and 20 mm gap transverse fracture. These fractures were reconstructed at the distal diaphysis of the femoral bone and computationally analysed through the finite element method under the stance phase condition. Findings showed a decrease in the fixation stiffness in large gap fracture (645.2 Nmm-1 for oblique and comminuted, while 23.4 Nmm-1 for the gap fracture), which resulted in higher displacement, IFM and stress distribution at the pin bone interface. These unfavourable conditions could consequently increase the risk of delayed union, pin loosening and infection, as well as implant failure. Nevertheless, the stress observed on the fracture surfaces was relatively low and in controlled amount, indicating that bone unity is still allowable in all models. Briefly, the unilateral fixation may provide desirable results in smaller fracture gap, but its usage in larger gap fracture might be alarming. These findings could serve as a guide and insight for surgeons and researchers, especially on the biomechanical stability of fixation in different fracture types and how will it affect bone unity.