Signal detection of immune thrombocytopenia associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13-131) and 9 days (range: 7-27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events.

Evaluating Safety and Durability of Adolescent Metabolic and Bariatric Surgery.

INTRODUCTION: Metabolic bariatric surgery (MBS) has demonstrated safety in its usage in the adolescent population and can aid in curbing the rising obesity epidemic. However, long-term data surrounding durability of MBS in this population is limited. This study aims to examine both short and long-term outcomes of MBS in adolescents, as well as identify patient characteristics and demographics that may impact operative safety and durability. METHODS: The New York Statewide Planning and Research Cooperative System was utilized to identify patients 12-19 y old who underwent a bariatric procedure from 2007 to 2018. Patients were followed for the need for revisional or conversion (RC) procedures. Safety was defined by 30-d readmission, length of stay (LOS), and in-hospital complications. Durability was characterized by the incidence of RC after the initial procedure. Variables that were significantly associated with each outcome on univariable analysis were selected for in multivariable regression models. RESULTS: 2241 adolescents underwent MBS in the study time frame; 58.46% of them underwent sleeve gastrectomy (SG). The median LOS was 1.66 ± 1.04 d. The overall in-hospital complication rate was 3.44%; 30-d readmission rate was 3.17%. Roux-en-Y Gastric Bypass (RYGB) patients were more likely to have a 30-d readmission than SG (OR = 1.75 95% CI 1.03-2.96). Factors associated with in hospital complications were preexisting hypertension (OR = 2.008 95% CI 1.141-3.535) and hypothyroidism (OR = 2.459 95% CI 1.132-5.341). Overall, the RC rate was 6.65%. RC rate following laparoscopic adjustable gastric banding (LAGB), RYGB, and SG was 27.33%, 2.08%, and 1.22%, respectively. The incidence of RC was significantly different between patients undergoing different types of bariatric surgery (P-value<0.0001), and it was significantly higher after LAGB comparing to RYGB (HR = 16.16, 95% CI: 7.56-34.51) as well as comparing to SG (HR = 9.22, 95% CI: 5.07-16.78). Insurance status, race or ethnicity, and socioeconomic disadvantage were not significantly associated with 30-d readmissions, in-hospital complications, LOS, or RC. CONCLUSIONS: Adolescent patients experience a low rate of postoperative adverse events following MBS. These procedures remain durable over time for this patient cohort. These positive results are regardless of race, ethnicity, and insurance status. This study identifies that female patients and LAGB patients are at highest risk for need for eventual RC, suggesting the need for closer postoperative follow-up for these specific patient cohorts.

Toxicity and Metabolomic Dysfunction Invoked by Febrifugin, a Harmful Component of Edible Nut of Swietenia macrophylla.

Swietenia macrophylla fruit is a valuable and historically significant medicinal plant with anti-hypertension and anti-diabetes. We identified a toxic component, Febrifugin, from the edible part of the nut following zebrafish toxicity-guided isolation. Febrifugin is a mexicanolide-type limonoid compound. The toxic factor induced acute toxicity in zebrafish, including yolk sac edema and pericardial edema, reduced body length, decreased melanin deposition, and presented acute skeletal developmental issues. Further exploration of the acute toxicity mechanism through metabolomics revealed that Febrifugin caused significant changes in 13 metabolites in zebrafish larvae, which are involved in the pentose phosphate, tricarboxylic acid (TCA) cycle, and amino acid biosynthesis. The bioassay of oxidative stress capacity and qRT-PCR measurement showed that the compound significantly affected the h6pd gene in the pentose phosphate pathway and the mRNA expression of cs, idh3a, fh, and shda genes in the TCA cycle, leading to reactive oxygen species (ROS) accumulation and a notable decrease in glutathione (GSH) activity in zebrafish. These findings provide a basis for the rational use of S. macrophylla as a medicinal plant and raise awareness of the safety of medicinal plants.

Quantitative CT analysis of idiopathic pulmonary fibrosis and correlation with lung function study.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. METHODS: We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. RESULTS: ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85-0.96). Additionally, with F% = 4.05% as the threshold, the Youden's J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P < 0.001), with a mean reduction of 2.45% per month. Quantitative CT indices correlated with all pulmonary function parameters except FEV1/FVC, with the highest correlation coefficients observed for F% and TLC%, FEV1%, FVC%, MVV% (r = - 0.571, - 0.520, - 0.521, - 0.555, respectively, all P-values < 0.001), and GGO% was significantly correlated with DLCO% (r = - 0.600, P < 0.001). Multiple stepwise linear regression analysis showed that F% was the best predictor of TLC%, FEV1%, FVC%, and MVV% (R2 = 0.301, 0.301, 0.300, and 0.302, respectively, all P-values < 0.001), and GGO% was the best predictor of DLCO% (R2 = 0.360, P < 0.001). CONCLUSIONS: Quantitative CT analysis can be used to diagnose IPF and assess lung function impairment. A decrease in the ASD may indicate disease progression.

Spatial Confinement of Lithium Borohydride in Bimetallic CoNi-Doped Hollow Carbon Frameworks for Stable Hydrogen Storage.

While lithium borohydride is one of the most promising hydrogen storage materials due to its ultrahigh hydrogen storage density, high thermodynamic stability, kinetic barriers, and poor reversibility, it is far from being used in practical applications. Herein, we prepare a cubic hollow carbon dodecahedron uniformly modified with a bimetallic CoNi alloy (CoNi/NC) for preserving the stable catalytic effect of CoNi alloys toward reversible hydrogen storage. It is theoretically confirmed that bimetallic CoNi alloys effectively weaken the B-H bonds of LiBH4 by extending their average length to 1.33, 0.09 and 0.04 Å longer than that of LiBH4 and LiBH4 under metallic Co, respectively. More importantly, the alloying of Co with Ni avoids the reattachment of H from LiBH4 to the Co surface, which prevents LiBH4 from dehydrogenation for the formation of H2 on the Co surface, thus resulting in an ultralow hydrogen desorption energy of 0.1, 1.85 and 0.52 eV lower than that of LiBH4 and LiBH4 under metallic Co. Therefore, the onset and peak hydrogen desorption temperatures decrease to 130 and 355 °C, respectively, 170 and 97 °C lower than that of bulk LiBH4. More importantly, a reversible H2 capacity of 9.4 wt % is achieved even after 10 cycles.

Hydrogen sulfide antagonizes cytokinin to change root system architecture through persulfidation of CKX2 in Arabidopsis.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which has been shown to play an important role in plant growth and development by coupling with various phytohormones. However, the relationship between H2S and cytokinin (CTK) and the mechanisms by which H2S and CTK affect root growth remain poorly understood. Endogenous CTK was analyzed by UHPLC-ESI-MS/MS. Persulfidation of cytokinin oxidase/dehydrogenases (CKXs) was analyzed by mass spectrometry (MS). ckx2/CKX2wild-type (WT), OE CKX2 and ckx2/CKX2Cys(C)62alanine(A) transgenic lines were isolated with the ckx2 background. H2S is linked to CTK content by CKX2, which regulates root system architecture (RSA). Persulfidation at cysteine (Cys)62 residue of CKX2 enhances CKX2 activity, resulting in reduced CTK content. We utilized 35S-LCD/oasa1 transgenic lines to investigate the effect of endogenous H2S on RSA, indicating that H2S reduces the gravitropic set-point angle (GSA), shortens root hairs, and increases the number of lateral roots (LRs). The persulfidation of CKX2Cys62 changes the elongation of cells on the upper and lower flanks of LR elongation zone, confirming that Cys62 of CKX2 is the specificity target of H2S to regulate RSA in vivo. In conclusion, this study demonstrated that H2S negatively regulates CTK content and affects RSA by persulfidation of CKX2Cys62 in Arabidopsis thaliana.

Protective effect of ferulic acid-hyaluronic acid copolymer against UVB irradiation in a human HaCaT cell line.

Excessive UVB exposure increased the production of reactive oxygen species (ROS), leading to oxidative damage and epidermal inflammation. To enhance UVB protection effect, a strong phenolic antioxidant, ferulic acid (FA) was designed onto HA via a free radical mediated method. Our previous work has confirmed its structural characterization and in vitro antioxidant. The aim of this study was to evaluate its protective effects against UVB-induced damage in human HaCaT cells. We observed a significant reduction in cell viability to 57.43 % following UVB exposure at a dose of 80 mJ/cm2. However, pretreatment with FA-HA (250 to 2000 µg·mL-1) significantly attenuated cytotoxicity in a dose-dependent manner. Furthermore, FA-HA was found to suppress the intracellular generation of ROS and up-regulated the expression of the antioxidant enzyme superoxide dismutase (SOD). The elevated levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as well as the mRNA expression of matrix metalloproteinase-1/9 (MMP-1/9) induced by UVB irradiation, were also effectively reduced by FA-HA. Additionally, FA-HA treatment decreases the phosphorylation of mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1), ultimately preventing apoptosis. These findings suggest that FA-HA is a promising candidate for UVB protection in skincare formulations.

Screening and preparation of highly active antioxidant peptides of apricot and their inhibitory effect on ultraviolet radiation.

In today's social environment, the objective reality of people's increasing life pressure, environmental deterioration, and enhanced ultraviolet rays caused by the destruction of the ozone layer has led to the aggravation of people's oxidative stress. Therefore, exogenous antioxidant peptides have become a hot topic in research. In the context of insufficient protein supply and resource recycling, almond meal was used as raw material in this study. As a by-product of oil processing, it has a protein content of 68 % and antioxidant-related amino acids accounted for 84.62 %, which can be used as a high-quality natural source of antioxidant peptides. Taking antioxidant activity as the only indicator, papain was screened as a hydrolase, and 7 antioxidant peptides such as YLSF, LPSYVN and SPHWNVN were separated and purified. The affinity energy of docking with Keap1-Nrf2-ARE protein molecules was -7.5--8.9 kal/mol, and hydrophobic stacking, hydrogen bonding and intermolecular forces were maintained. Seven antioxidant peptides were synthesized in solid phase, and the IC50 values of in vitro ABTS+ scavenging rates were 3.59 µg/mL-6.73 µg/mL, and the antioxidant capacity was stronger than that of glutathione and ascorbic acid. In the in vitro cellular ROS scavenging capacity, all seven peptides had the effect of scavenging intracellular ROS, among which YLSF and ESWNPRDPQF had stronger scavenging capacity than glutathione. Finally, the mouse skin staining method determined that apricot antioxidant peptides had a significant inhibitory effect on UV damage to mouse skin, and targeted proteomics was used to clarify that apricot antioxidant peptides inhibited UV damage by mainly affecting three pathways, including the base excision repair pathway. This study not only improved the economic value of processing by-products, but also obtained 7 highly active almond antioxidant peptides, tapping the potential ability of apricot antioxidant peptides to be incorporated into functional food or cosmetic formulations.

The impact of online interaction and information technology accessibility on academic engagement among international undergraduate students in Chinese universities: The mediating effect of learning interest.

Academic engagement was recognized as a crucial predictor to measure the effectiveness of online teaching of international students. Therefore, this study established a mediating model to explore the mechanism underlying of interaction and information technology accessibility on academic engagement of international students, as well as the impact of learning interest on these mechanisms with the context of online teaching. Using a stratified random sampling method, 1895 international students from 32 Chinese universities were selected. These international students had completed the academic engagement scale, interaction scale, information technology accessibility scale, and learning interest scale. The study variables were analyzed in sequence for reliability and validity, common method biases test, correlation analysis, structural equation model testing, and bias-corrected percentile Bootstrap testing. The results revealed that online interaction positively affected the academic engagement of international students in Chinese universities (ß= 0.35, p < 0.001), and learning interest played a partial mediating role between online interaction and academic engagement (indirect effect = 0.10, 95 % Boot CI = [0.06, 0.13], p < 0.001). Information technology accessibility did not have a direct impact on academic engagement (ß= 0.06, p > 0.05); but learning interest played a complete mediating role between information technology accessibility and academic engagement (indirect effect = 0.09, 95 % Boot CI = [0.05, 0.11], p < 0.001). The results of Bootstrap showed that the mediating effects within the model were significant. The findings of this study explored the potential mechanism underlying the online academic engagement of international students in Chinese universities, and provided empirical evidence for universities and educators to implement differentiated learning support, assist international students in adapting to online learning styles, and stimulate the endogenous motivation of students' learning.

The JA-to-ABA signaling relay promotes lignin deposition for wound healing in Arabidopsis.

Plants are frequently exposed to herbivory and mechanical damage that result in wounding. Two fundamental strategies, regeneration and healing, are employed by plants upon wounding. How plants make different decisions and how wound healing is sustained until the damaged tissues recover are not fully understood. In this study, we found that local auxin accumulation patterns, determined by wounding modes, may activate different recovery programs in wounded tissues. Wounding triggers transient jasmonic acid (JA) signaling that promotes lignin deposition in the first few hours after wounding occurs. This early response is subsequently relayed to ABA signaling via MYC2. The induced JA signaling promotes ABA biosynthesis to maintain the expression of RAP2.6, a key factor for sustained lignin biosynthesis and the later wound-healing process. Our findings provide mechanistic insights into how plants heal from wounding and clarify the molecular mechanisms that underlie the prolonged healing process following wounding.

E-cigarette use and associated factors among adults aged 18-44 years in China: Findings from an online survey.

INTRODUCTION: There needs to be more up-to-date evidence on the prevalence of e-cigarette use among Chinese adults. This study aims to investigate the prevalence and associated factors of e-cigarette use among adults aged 18-44 years in China. METHODS: Cross-sectional design and convenience sampling were used. The data for this study were obtained from an online survey conducted in mainland China from April to May 2023. The target population was adults aged 18-44 years. Descriptive analysis was employed to report the prevalence of e-cigarette use, while adjusted multivariable logistic regression was performed to examine the association between e-cigarette use and related factors. RESULTS: A total of 4256 participants were included in this study; 12.9% were current e-cigarette users, 5.9% were frequent users, and 7.0% were occasional users. The descriptive analysis results indicated that males and cigarette users had a higher prevalence of e-cigarette use. Multivariable analysis showed that e-cigarette use was significantly associated with female gender (AOR=0.76, 95% CI: 0.60-0.96), those aged 25-34 years with monthly income 6000-8999 CNY (AOR=2.01; 95% CI: 1.18-3.41), those aged 25-34 years with monthly income ≥9000 CNY (AOR=2.20; 95% CI: 1.26-3.82), college or undergraduate degree (AOR=1.91; 95% CI: 1.22-3.00), urban residence (AOR=1.72; 95% CI: 1.34-2.20), being a current smoker (AOR=3.32; 95% CI: 2.64-4.16), perception of harm (AOR=0.66; 95% CI: 0.60-0.73), and perception of benefit (AOR=2.31; 95% CI: 2.04-2.61). CONCLUSIONS: The prevalence of current e-cigarette use among adults in China was 12.9% within our sample. In addition to sociodemographic factors, individuals with a higher perception of the harm associated with e-cigarettes were less likely to engage in e-cigarette consumption. Conversely, individuals who perceive the 'benefits' of e-cigarettes more favorably use them. Targeted interventions, such as health education, are recommended to help adults develop a correct understanding of e-cigarettes and lower the prevalence of e-cigarette use.

Analysis of okadaic acid using electrochemiluminescence imaging on microfluidic biosensing chip.

The sensitivity and specificity of electrochemiluminescence (ECL)-based biosensor directly rely on the property of luminophor, the type of sensing carriers and the effectiveness of signal amplification used in the sensor design, which poses a major challenge to manage these elements simultaneously. In this work, an aggregation-induced electrochemiluminescence (AIECL) microfluidic sensing chip using 4',4″,4‴,4‴'-(ethene-1,1,2,2-tetrayl)tetrabiphenyl-4-carboxylic acid (TPE)-derived hafnium-based metal-organic framework (Hf-MOF) as emitter was developed. An easily overlooked marine pollutant, okadaic acid (OA) with different concentrations ranging from 5.00 ng/mL to 1.50 × 104 ng/mL at the electrode is visualized imaging benefit from high luminescence efficiency of Hf-MOF coupled the rolling circle amplification strategy assisted by trans-cleavage activity of CRISPR/Cas12a. These highlights will solve the long-lasting task in the accurate analysis of small molecule pollutants, which can be able to provide more worthy reference solution about construction of novel ECL luminophor and signal extraction of low-abundance disease-related biomarkers.

The relationship between MRI-detected hip abnormalities and hip pain in hip osteoarthritis: a systematic review.

Magnetic resonance imaging (MRI) is increasingly used in the classification and evaluation of osteoarthritis (OA). Many studies have focused on knee OA, investigating the association between MRI-detected knee structural abnormalities and knee pain. Hip OA differs from knee OA in many aspects, but little is known about the role of hip structural abnormalities in hip pain. This study aimed to systematically evaluate the association of hip abnormalities on MRI, such as cartilage defects, bone marrow lesions (BMLs), osteophytes, paralabral cysts, effusion-synovitis, and subchondral cysts, with hip pain. We searched electronic databases from inception to February 2024, to identify publications that reported data on the association between MRI features in the hip joint and hip pain. The quality of the included studies was scored using the Newcastle-Ottawa Scale (NOS). The levels of evidence were evaluated according to the Cochrane Back Review Group Method Guidelines and classified into five levels: strong, moderate, limited, conflicting, and no evidence. A total of nine studies were included, comprising five cohort studies, three cross-sectional studies, and one case-control study. Moderate level of evidence suggested a positive association of the presence and change of BMLs with the severity and progress of hip pain, and evidence for the associations between other MRI features and hip pain were limited or even conflicting. Only a few studies with small to modest sample sizes evaluated the association between hip structural changes on MRI and hip pain. BMLs may contribute to the severity and progression of hip pain. Further studies are warranted to uncover the role of hip MRI abnormalities in hip pain. The protocol for the systematic review was registered with PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ , CRD42023401233).

Study on the adsorption performance of fly ash loaded on nano-FeS for chromium-containing wastewater treatment.

In view of the problems caused by chromium-containing wastewater, such as environmental pollution, biological toxicity, and human health risks. Based on fly ash adsorption and nano-FeS reduction characteristics, fly ash loaded nano-FeS composite (nFeS-FA) was synthesized using mineral supported modification technology and ultrasonic precipitation method. The effect of adsorbent dosage, initial pH, contact time, and initial concentration of the solution on the adsorption of Cr(VI) and total Cr by nFeS-FA was investigated. The characteristics of Cr(VI) and total Cr adsorption by nFeS-FA were studied using adsorption isotherms, adsorption kinetics principles, as well as XRD, TEM, SEM-EDS, and BET analysis. The results demonstrated that under the conditions of nFeS-FA of 8 g/L, initial pH of 4, contact time of 150 min, and initial concentration of the solution at 100 mg/L, nFeS-FA achieved removal efficiency of 87.85 % for Cr(VI) and 71.77 % for total Cr. The adsorption of Cr(VI) and total Cr by nFeS-FA followed the Langmuir model and pseudo-second-order kinetic model, indicating monolayer adsorption with chemical adsorption as the dominant mechanism. XRD, TEM, SEM-EDS, and BET revealed that the flaky nano-FeS was uniformly distributed on the surface of fly ash, exhibiting good dispersion and thereby increasing the specific surface area. During the adsorption experiments, nFeS-FA reacted with Cr(VI), and the generated Fe3+ mainly existed as FeOOH precipitation, while S2- reacted with Cr(III) to produce Cr2S3 precipitation. Therefore, nFeS-FA exhibited excellent adsorption performance towards Cr(VI) and total Cr. It can serve as a technological reference for the remediation of heavy metal chromium pollution in the field of water treatment.

rTMS for Poststroke Pusher Syndrome: A Randomized, Patient-Blinded Controlled Clinical Trial.

BACKGROUND: Patients with poststroke pusher syndrome (PS) require longer duration of rehabilitation and more supplemental care after discharge. Effective treatment of PS remains a challenge. The role of repetitive transcranial magnetic stimulation (rTMS) for PS has not been examined. OBJECTIVE: Assess the efficacy of rTMS for patients with poststroke PS in reducing pushing behavior, enhancing motor recovery and improving mobility. METHODS: A randomized, patient- and assessor-blinded sham-controlled trial with intention-to-treat analysis was conducted. Thirty-four eligible patients with poststroke PS were randomly allocated to receive either rTMS or sham rTMS for 2 weeks. Pushing behavior on the Burke lateropulsion scale and scale for contraversive pushing, motor function on Fugl-Meyer assessment scale-motor domain (FMA-m) and mobility on modified Rivermead mobility index were measured at baseline, 1 and 2 weeks after intervention. Repeated-measures analysis of covariance was used for data analysis. RESULTS: There was no significant interaction between intervention and time on Burke lateropulsion scale (F = 2.747, P = .076), scale for contraversive pushing (F = 1.583, P = .214), or change of modified Rivermead mobility index (F = 1.183, P = .297). However, a significant interaction between intervention and time was observed for FMA-m (F = 5.464, P = .019). Post hoc comparisons of FMA-m show better improvement in rTMS group with mean differences of 12.7 (95% CI -7.3 to 32.7) and 15.7 (95% CI -4.6 to 36.0) at post-treatment week 1 and week 2 respectively. CONCLUSIONS: rTMS did not demonstrate significant efficacy in improving pushing behavior and mobility in patients with PS. However, rTMS might have potential effect in enhancing motor function for patients with PS. REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200058015 at http://www.chictr.org.cn/searchprojen.aspx) on March 26, 2022.

FOXM1 mediates methotrexate resistance in osteosarcoma cells by promoting autophagy.

Osteosarcoma (OS) is a primary bone cancer mostly found in adolescents and elderly individuals. The treatment of OS is still largely dependent on traditional chemotherapy. However, the high incidence of drug resistance remains one of the greatest impediments to limiting improvements in OS treatment. Recent findings have indicated that the transcription factor FOXM1 plays an important role in various cancer-related events, especially drug resistance. However, the possible role of FOXM1 in the resistance of OS to methotrexate (MTX) remains to be explored. Here, we find that FOXM1, which confers resistance to MTX, is highly expressed in OS tissues and MTX-resistant cells. FOXM1 overexpression promotes MTX resistance by enhancing autophagy in an HMMR/ATG7-dependent manner. Importantly, silencing of FOXM1 or inhibiting autophagy reverses drug resistance. These findings demonstrate a new mechanism for FOXM1-induced MTX resistance and provide a promising target for improving OS chemotherapy outcomes.

Mortality and disease burden of oral cancer in China: a time-trend analysis on the China Death Surveillance Database from 2006 to 2021.

BACKGROUND: Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control. METHODS: Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden. RESULTS: From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: - 0.97%; 95% CI: - 1.89%, - 0.04%), and the similar trend was observed among females (AAPC: - 1.22%; 95% CI: - 1.89%, - 0.55%). The ASMR of males was 2.31-3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: - 1.31%, 95% CI: - 2.24% ~ - 0.37%) and for female (AAPC: - 1.63%, 95% CI: - 2.30% ~ - 0.95%). ASMR in urban areas was 1.02-1.28 times higher than that in rural areas from 2006 to2011, but 0.85-0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021. CONCLUSIONS: There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.

Automated classification of angle-closure mechanisms based on anterior segment optical coherence tomography images via deep learning.

Purpose: To develop and validate deep learning algorithms that can identify and classify angle-closure (AC) mechanisms using anterior segment optical coherence tomography (AS-OCT) images. Methods: This cross-sectional study included participants of the Handan Eye Study aged ≥35 years with AC detected via gonioscopy or on the AS-OCT images. These images were classified by human experts into the following to indicate the predominant AC mechanism (ground truth): pupillary block, plateau iris configuration, or thick peripheral iris roll. A deep learning architecture, known as comprehensive mechanism decision net (CMD-Net), was developed to simulate the identification of image-level AC mechanisms by human experts. Cross-validation was performed to optimize and evaluate the model. Human-machine comparisons were conducted using a held-out and separate test sets to establish generalizability. Results: In total, 11,035 AS-OCT images of 1455 participants (2833 eyes) were included. Among these, 8828 and 2.207 images were included in the cross-validation and held-out test sets, respectively. A separate test was formed comprising 228 images of 35 consecutive patients with AC detected via gonioscopy at our eye center. In the classification of AC mechanisms, CMD-Net achieved a mean area under the receiver operating characteristic curve (AUC) of 0.980, 0.977, and 0.988 in the cross-validation, held-out, and separate test sets, respectively. The best-performing ophthalmologist achieved an AUC of 0.903 and 0.891 in the held-out and separate test sets, respectively. And CMD-Net outperformed glaucoma specialists, achieving an accuracy of 89.9 % and 93.0 % compared to 87.0 % and 86.8 % for the best-performing ophthalmologist in the held-out and separate test sets, respectively. Conclusions: Our study suggests that CMD-Net has the potential to classify AC mechanisms using AS-OCT images, though further validation is needed.

Study on the adsorption performance of modified high silica fly ash for methylene blue.

Presently, there are several issues associated with solid waste fly ash, such as its accumulation and storage, low comprehensive utilization rate, lack of high-value utilization technology, environmental risk and ecological impact. Thus, based on the high silica content and adsorption characteristics of fly ash, two novel adsorbents, namely mesoporous silica-based material (MSM) and sodium dodecyl sulfate-modified fly ash (SDS-FA), were prepared using an ultrasound-assisted alkali fusion-hydrothermal method and surface modification method. Furthermore, effects of adsorbent dosage, initial pH, contact time, and initial concentration of the solution on the adsorption of the organic pollutant methylene blue (MB) by fly ash, MSM, and SDS-FA were investigated to select the optimal modified high silica fly ash adsorbent. Based on the adsorption isotherms and adsorption kinetics, together with SEM, XRD, FTIR and BET analyses, the adsorption mechanism of MSM for MB was revealed. The results showed that under the conditions of an adsorbent dosage of 2 g L-1, initial pH of 9, contact time of 150 min, and initial concentration of 100 mg L-1, MSM and SDS-FA exhibited removal efficiencies of 92.69% and 84.64% for MB, respectively, which were significantly higher than that of fly ash alone. The adsorption of MB by MSM and SDS-FA followed the Langmuir model and pseudo-second-order kinetics, indicating monolayer adsorption with chemical adsorption as the dominant mechanism. The mechanism of the adsorption of MB by MSM is mainly the result of the synergistic effect among its increased specific surface area, hydrogen bonding, ion exchange, and electrostatic interactions. After five cycles of adsorption-desorption process, the removal efficiency of MSM for MB consistently remained above 80%. Therefore, MSM can serve as a valuable reference for the resource utilization of fly ash and remediation of dye-polluted wastewater.

1,1,2,2-Tetra(4-carboxylphenyl)ethylene-Based Metal-Organic Gel as Aggregation-Induced Electrochemiluminescence Emitter for the Detection of Aflatoxin B1 Based on Nanosurface Energy Transfer.

In this Letter, a sensitive DNA sensing platform was developed using an indium-ion-coordinated 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) metal-organic gel (In-MOG) as an aggregation-induced electrochemiluminescence (AIECL) emitter and nanosurface energy transfer (NSET) as an efficient quenching strategy for detecting aflatoxin B1 (AFB1), the most dangerous food toxin. The coordination occurred in indium ions, and carboxyl groups restricted the internal rotation and vibration of TPE molecules, forcing them to release photons via radiative transitions. The quenchers of microfluidic-produced gold nanoparticles were embedded in a long-tailed triangular DNA structure, where the quenching phenomenon aligned with the theory of ECL-NSET under the overlap of spectra and appropriate donor-acceptor spacing. The proposed analytical method showed a sensitive ECL response to AFB1 in the wide concentration range of 0.50-200.00 ng/mL with a limit of detection of 0.17 ng/mL. Experimental results confirmed that constraining luminescent molecules using coordination and bonding to trigger the AIECL phenomenon was a promising method to prepare signal labels for the trace detection of food toxins.