Bioaccessibility and health risk assessment of hydrophobic organic pollutants in soils from four typical industrial contaminated sites in China.

There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27‒14.3 ng/g) and OPFRs (6.30‒310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.

Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021.

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels. Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations. Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate. Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East. Funding: None.

Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Global, regional, and national burden and trends of migraine among youths and young adults aged 15-39 years from 1990 to 2021: findings from the global burden of disease study 2021.

BACKGROUND: Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15-39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. METHODS: Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. RESULTS: Between 1990 and 2021, the worldwide prevalence of migraine among 15-39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35-39 age group. Notably, female rates consistently exceeded male rates across all age categories. CONCLUSION: The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.

Correlation between cancer-related cognitive impairment and resting cerebral glucose metabolism in patients with ovarian cancer.

Background: An increasing number of research have applied neuroimaging techniques to explore the potential neurobiological mechanism of Cancer-related cognitive impairment (CRCI). Purpose: To explore the correlation between resting brain glucose metabolism and CRCI using 18F-FDG PET/CT in ovarian cancer (OC) patients. Methods: From December 2021 to March 2022, 38 patients with OC were selected as the study group, and 38 healthy women of the same age (±1 year) who underwent routine physical examination using PET/CT were selected as the control group. Patients received further assessment with the Montreal Cognitive Assessment Scale (MoCA) and Perceived Deficit Questionnaire (PDQ). Independent sample t-test and Spearman correlation were conducted for data analysis. Results: The resting brain glucose metabolism in the OC group was significantly lower than in the healthy controls. 60.52 % patients had neuropsychological impairment and retrospective memory were the most serious perceived cognitive impairments. The resting brain glucose metabolism in OC patients did not significantly correlate with neuropsychological performance but had significant positive correlation with subjective cognitive evaluation. Discussion: Resting glucose metabolism was low in OC patients and associated with subjective cognitive impairment but not objective neuropsychological test results. 18F-FDG PET/CT can be used to evaluate brain function in OC patients and provide reliable imaging indicators for early recognition of and intervention for changes in cognitive function.

Incorporating body mass index into esophageal manometry metrics and mean nocturnal baseline impedance for the evaluation of gastro-esophageal reflux disease.

This study aims to enhance the effectiveness of high resolution manometry (HRM) and pH-impedance monitoring metrics in distinguishing between gastro-esophageal reflux disease (GERD) and non-GERD. A retrospective propensity score matching (PSM) study was conducted on 643 patients with GERD symptoms. PSM matched 134 GERD patients with 134 non-GERD controls. Body mass index (BMI), intra-esophageal pressure (IEP) and intra-gastric pressure (IGP) were significantly higher in the GERD group compared to the non-GERD group. BMI was correlated with IEP and IGP positively. IGP was positively correlated with esophagogastric (EGJ) pressure (EGJ-P) in participants with EGJ type 1 and 2, but not in participants with EGJ type 3. BMI was correlated with distal MNBI negatively. Logistic regression showed BMI as an independent risk factor for GERD. Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) showed that BMI adjusted EGJ contractile integral (EGJ-CI) and BMI adjusted MNBI were superior to the corresponding original ones in predicting GERD susceptibility. According to the findings, BMI and IGP are the main factors contributing to the development of GERD. BMI affects IEP through the adaptive response of EGJ-P to IGP. Incorporating BMI into the calculations of EGJ-CI and MNBI can improve their ability in predicting GERD susceptibility.

Vertically Fluorinated Graphene Encapsulated SiOx Anode for Enhanced Li+ Transport and Interfacial Stability in High-Energy-Density Lithium Batteries.

Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

New Sweet-Tasting Gypenosides from "Jiaogulan" (Gynostemma pentaphyllum) and Their Interactions with the Homology Model of Sweet Taste Receptors.

Gynostemma pentaphyllum has been used as an herbal tea, vegetable, and dietary supplement for hundreds of years in East Asia. The sweet variety, grown in large areas in Fujian Province, China, is an essential source of "Jiaogulan" herbal tea. However, its sweet components are unknown. To investigate the sweet constituents of Fujian "Jiaogulan" and discover new natural high-potency sweeteners, phytochemical and sensory evaluations were combined to obtain 15 saponins, of which 11 (1-11) were sweet-tasting, including 2 new ones with sweetness intensities 20-200 times higher than that of sucrose, and four (12-15) were bitter-tasting. Their structures were elucidated using spectroscopic methods (NMR, MS, IR, UV), hydrolysis, and comparison with literature data. The contents of the 15 saponins were quantitatively analyzed using UPLC-MS/MS in multiple reaction monitoring mode. The contents of 1 and 2 sweet-tasting gypenosides were 9.913 ± 1.735 and 35.852 ± 1.739 mg/kg, respectively. The content of the sweetest compound (6) was 124.969 ± 0.961 mg/kg. Additionally, compound 4 was the most abundant sweet component (422.530 ± 3.702 mg/kg). Furthermore, molecular docking results suggested interactions of sweet saponins with sweet taste receptors. In general, this study revealed the material basis of the Fujian "Jiaogulan" taste.

Measurement error in hydrostatic leveling system due to temperature effect and their reduction method.

Temperature is a crucial factor influencing the accuracy of the hydrostatic leveling system (HLS), necessitating a temperature compensation test for HLS. This paper investigates HLS temperature compensation through theoretical correction and experimental verification. The influence of temperature on the accuracy of hydrostatic level products is determined through temperature tests on 34 hydrostatic level products. The optimal temperature compensation formula is derived using the non-linear curve fitting method. The HLS is enhanced with a temperature compensation algorithm and temperature sensor, resulting in a new, high-precision, and high-stability hydrostatic leveling product with temperature compensation. Experimental findings reveal that the stability of the improved hydrostatic leveling product exceeds 30% compared to products on the market and surpasses 70% compared to the original products.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

Density of tertiary lymphoid structures predicts clinical outcome in breast cancer brain metastasis.

BACKGROUND: Patients with breast cancer brain metastases (BCBM) experience a rapid decline in their quality of life. Recently, tertiary lymphoid structures (TLSs), analogs of secondary lymphoid organs, have attracted extensive attention. However, the potential clinical implications of TLSs in BCBMs are poorly understood. In this study, we evaluated the density and composition of TLSs in BCBMs and described their prognostic value. METHODS: Clinicopathological data were collected from 98 patients (2015-2021). TLSs were evaluated, and a TLS scoring system was constructed. Differences in progression-free survival (PFS) and overall survival (OS) between groups were calculated using the Kaplan-Meier method. Immunohistochemistry and multiplex immunofluorescence (mIF) were used to assess TLSs heterogeneity. RESULTS: TLSs were identified in 47 patients with BCBM. High TLSs density indicated favorable survival (OS, p=0.003; PFS, p<0.001). TLS was positively associated with OS (p=0.0172) and PFS (p=0.0161) in the human epidermal growth factor receptor type 2-positive subtype, and with prolonged OS (p=0.0482) in the triple-negative breast cancer subtype. The mIF results showed significant differences in the percentages of T follicular helper (Tfh) cells, M2 macrophages, cytotoxic T lymphocytes, and CD8+TIM-3+ T lymphocytes between the groups of TLS scores 0-3 (cytotoxic T lymphocytes, p=0.044; Tfh, p=0.021; M2 macrophages, p=0.033; CD8+TIM-3+ T lymphocytes, p=0.018). Furthermore, novel nomograms incorporating the TLS scores and other clinicopathological predictors demonstrated prominent predictability of the 1-year, 3-year, and 5-year outcomes of BCBMs (area under the curve >0.800). CONCLUSION: Our results highlight the impact of TLSs abundance on the OS and PFS of patients with BCBM. Additionally, we described the immune composition of TLSs and proposed novel nomograms to predict the prognosis of patients with BCBM.

Electroacupuncture activates the peroxisome proliferators-activated receptor pathway to improve the phenotype of cerebral palsy.

AIM: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague-Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. METHODS: Gait analysis and Y-maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. RESULTS: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. CONCLUSION: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP.

Three-Dimensional Computed Tomography Scanning Study of the Superior Labial Artery in Chinese Individuals for Assessing Filler Injection Safety.

BACKGROUND: Lip filler injection is one of the most common minimally invasive cosmetic procedures involving the face; however, vascular complications are not uncommon. The aim of this study was to investigate the anatomy of the superior labial artery (SLA) and provide precise topographic information for dermal filler injection into the lips. METHODS: Computed tomography (CT) scans of 52 cadaveric heads injected with lead oxide were obtained. We then used Mimics software to construct 3D images of the SLA described by a coordinate system based on the bilateral external auditory canal and the left orbit. This study aimed to classify the SLA in the Han Chinese population, measure its diameter at specific points, and determine the thickness of the lip at those points. Ultimately, we utilized a thermal imaging technique to illustrate the course and depth of the SLA within the lip. The objective of this study was to provide safe guidance for clinical injections. RESULTS: In this study, the SLA was successfully identified in all cadavers. The mean overall diameter of the superior labial arteries was 1.36 ± 0.28 mm. The superior labial artery showed a general course from deep to shallow with an average depth of 5.68 ± 1.68 mm from the oral commissure to the midline. CONCLUSIONS: There are anatomical differences in the superior labial arteries among Chinese people. Furthermore, 3D CT images can digitally elucidate the exact positions of the superior labial artery via a coordinate system, improving the safety of upper lip filler injections in clinical settings. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways.

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.

Correction: MiR-181b-5p Downregulates NOVA1 to Suppress Proliferation, Migration and Invasion and Promote Apoptosis in Astrocytoma.

[This corrects the article DOI: 10.1371/journal.pone.0109124.].

Cross-linked Sodium Hyaluronate Gel with PLLA-b-PEG Microsphere for Facial Contouring in Chinese: A Retrospective Study.

BACKGROUND: In Asia, the demand for cosmetic facial treatments has surged due to technological advancements, increased social acceptability, and affordability. Poly-L-lactic acid (PLLA) fillers, known for their biocompatibility and biodegradability, have emerged as a popular choice for facial contouring, yet studies specifically addressing their use in Asian populations are scarce. METHODS: This retrospective study examined 30 Chinese patients who underwent facial contouring with PLLA fillers, focusing on product composition, injection techniques, and safety measures. A comprehensive clinical evaluation was performed, including the Global Aesthetic Improvement Scale (GAIS) and Global Impression of Change Scale (GICS) for effectiveness and patient satisfaction, respectively. RESULTS: No significant difference in GAIS scores was observed between injectors and blinded evaluators over a 12-month period, indicating consistent effectiveness. Patient satisfaction remained high, with GICS scores reflecting positive outcomes. The safety profile was favorable, with no serious adverse events reported. The study highlighted the importance of anatomical knowledge to avoid complications, particularly in areas prone to blindness. CONCLUSIONS: PLLA fillers offer a safe, effective option for facial contour correction in the Asian population, achieving high patient satisfaction and maintaining results over time. The study underscores the need for tailored approaches in cosmetic procedures for Asians, considering their unique facial structures and aesthetic goals. Further research with larger, multicenter cohorts is recommended to validate these findings and explore long-term effects. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Icariin protects against acute graft-versus-host disease while preserving graft-versus-leukemia activity after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGVHD), which is mainly mediated by allogeneic T cells, is a decisive factor in the success of allogeneic hematopoietic stem cell transplantation (allo-HCT). Prophylaxis for aGVHD in clinical patients is unsatisfactory, and there is still a huge unmet need for novel approaches. Icariin (ICA) shows potent anti-inflammatory activity and suppresses T cell-mediated immune responses. Thus, ICA is a potential drug for the prevention of aGVHD. However, there is no data assessing the impact of ICA on aGVHD after allo-HCT. PURPOSE: This study aimed to investigate the protective effect of ICA against aGVHD and its mechanisms. Moreover, the impact of ICA on the graft-versus-leukemia (GVL) effect and engraftment of donor hematopoietic and immune cells were assessed. METHODS: Different murine models of allo-HCT were developed to study the influence of the ICA on GVHD and GVL effect. Flow cytometry was used to analyze the growth of leukemia cells, alterations in different immune cells, and apoptosis. Cell proliferation was determined using a CCK-8 assay. RNA sequencing and quantitative proteomic analysis were performed to elucidate the underlying mechanisms, which were further verified by polymerase chain reaction or functional experiments. RESULTS: Different concentrations of ICA exhibited opposite effects: low-concentration ICA promoted, while high concentrations suppressed the proliferation and function of T cells. A high dose of ICA administration during days +3 to +5 post-allo-HCT can alleviate murine aGVHD but does not affect the course of chronic GVHD (cGVHD), the GVL effect against both acute myeloid and lymphoblastic leukemia, or the recovery of donor hematological and immune cells. ICA extensively represses the expansion, function, and infiltration of donor alloreactive T cells, while preserving regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Quantitative proteomic analysis showed that downregulation of integrin-linked kinase (ILK) and lymphocyte cytosolic protein 2 (LCP2) expression was possibly associated with ICA-mediated aGVHD protective effects. Furthermore, an inhibitor of ILK, which can alleviate murine aGVHD administered early after allo-HCT. CONCLUSION: These findings suggest that the bioactivities of ICA are associated with its concentration and that ICA can effectively mitigate aGVHD without losing GVL activity or engraftment of donor hematopoietic and immune cells. Thus, ICA may be a promising drug for preventing aGVHD in clinical settings.

From 2e- to 4e- pathway in the alkaline oxygen reduction reaction on Au(100): Kinetic circumvention of the volcano curve.

We report the free energy barriers for the elementary reactions in the 2e- and 4e- oxygen reduction reaction (ORR) steps on Au(100) in an alkaline solution. Due to the weak adsorption energy of O2 on Au(100), the barrier for the association channel is very low, and the 2e- pathway is clearly favored, while the barrier for the O-O dissociation channel is significantly higher at 0.5 eV. Above 0.7 V reversible hydrogen electrode (RHE), the association channel becomes thermodynamically unfavorable, which opens up the O-O dissociation channel, leading to the 4e- pathway. The low adsorption energy of oxygenated species on Au is now an advantage, and residue ORR current can be observed up to the 1.0-1.2 V region (RHE). In contrast, the O-O dissociation barrier on Au(111) is significantly higher, at close to 0.9 eV, due to coupling with surface reorganization, which explains the lower ORR activity on Au(111) than that on Au(100). In combination with the previously suggested outer sphere electron transfer to O2 for its initial adsorption, these results provide a consistent explanation for the features in the experimentally measured polarization curve for the alkaline ORR on Au(100) and demonstrate an ORR mechanism distinct from that on Pt(111). It also highlights the importance to consider the spin state of O2 in ORR and to understand the activation barriers, in addition to the adsorption energies, to account for the features observed in electrochemical measurements.