Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children.

BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

Dietary risk assessment of benzophenone derivatives using bread consumption estimates in a Taiwanese population.

Listed as endocrine-disrupting chemicals, benzophenone (BP) and its nine analogues (BPs) are an emerging group of contaminants. The migration of BPs from ultraviolet inks to food has been investigated in many studies; however, few studies have investigated BPs in foods and the risks of human exposure to BPs. We validated a trace and multi-residue method for simultaneously determining 10 BPs, including BP, BP-1, BP-2, BP-3, BP-8, 4-MBP, 2-OHBP, 4-OHBP, M2BB, and PBZ. Eighty-one bread samples were analyzed using stable isotope labeling and ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with solid-liquid extraction. We determined the estimated daily intake of BPs, non-cancer risks, and lifetime cancer risks (LTCRs) from daily bread consumption for seven age groups using a Monte Carlo simulation. The method demonstrated robust linearity (R2 ≥ 0.991), low limits of detection (0.04-2 ng/g), and satisfactory precision. The intra- and interday relative standard deviation ranges were 0.6%-9% and 3%-20%, respectively. BP, 4-MBP, 2-OHBP, BP-1, and BP-3 were detected in 97%, 67%, 59%, 24%, and 23% of the samples, respectively. 2-OHBP had the highest mean (range) value of 18.3 (

The downregulation of miR-509-3p expression by collagen type XI alpha 1-regulated hypermethylation facilitates cancer progression and chemoresistance via the DNA methyltransferase 1/Small ubiquitin-like modifier-3 axis in ovarian cancer cells.

BACKGROUND: MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC. METHODS: The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study. RESULTS: Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity. CONCLUSION: The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.

Assessment of various conditions for the simultaneous determination of US EPA and EU priority PAHs in coffee samples and their PAHs consumption risk.

The optimal conditions for simultaneous determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) in coffee beans and coffee brews were developed. The QuEChERS (quick, easy, cheap, effective, rugged and safe) technology combined with high performance liquid chromatography - temperature-controlled fluorescence detection and gas chromatography - tandem mass spectrometry were used in the investigation. PAHs could be determined in commercially available green coffee beans (possibly caused by environmental contamination), and their PAHs content increased with the degree of roasting. Coffee beans brewed with the coffee machine released more PAHs into their brews than those brewed with the drip bag. The PAHs consumption risk of the brewed coffee samples was not high due to their low PAH level. Nevertheless, the methods of roasting and brewing and the amount of drinking could still be considered to reduce the intake of PAHs.

The Downregulation of miR-509-3p Expression by Collagen Type XI Alpha 1-Regulated Hypermethylation Facilitates Cancer Progression and Chemoresistance via the DNA Methyltransferase 1/Small Ubiquitin-like Modifier-3 Axis in Ovarian Cancer Cells.

Background MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC. Methods The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study. Results Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) phosphorylation and stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity. Conclusion The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.

Effect of icariin on the H2O2-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis.

Icariin exerts antioxidative and anti-inflammatory effects and is used in the treatment of bronchial asthma. However, the specific modes of action are uncertain. In this study, we investigated whether icariin could modulate the silencing information regulator 2-related enzyme 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) axis by regulating miR-138-5p during H2O2-induced proliferation of mouse airway smooth muscle cells (ASMCs). Primary BALB/c mouse ASMCs were cultured using the tissue block adherence method and were induced with hydrogen peroxide (H2O2; 200 µmol/L) to establish a bronchial asthma ASMC proliferation model. With the aid of Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) in H2O2-induced ASMCs, the expression of miR-138-5p, SIRT1, AMPK, PGC-1α, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), collagen I, and collagen III protein and mRNA were investigated. The proliferation rate and activities of superoxide dismutase1 (SOD1), reduced glutathione (GSH), malonaldehyde (MDA), and reactive oxygen species (ROS) in ASMCs were determined. The results suggest Compared with the H2O2-induced group, icariin inhibited the miR-138-5p expression; enhanced SIRT1, p-AMPK, and PGC-1α expression; attenuated MDA activity and ROS level; lowered TGF-ß1, collagen I, and collagen III expression levels; and decreased the proliferation of ASMCs induced by H2O2. The dual-luciferase reporter gene assay results showed that SIRT1 is a regulatory target of miR-138-5p.The results suggest that Icariin could improve the H2O2-induced proliferation of ASMCs. The mechanism may be related to the increase of activation of SIRT1/AMPK/PGC-1α axis by suppressing the expression of miR-138-5p. Thus, SIRT1 is the regulatory target of miR-138-5p.

Desmoid-type fibromatosis mimicking uterine fibroid invade the urinary bladder: A case report and literature review.

OBJECTIVE: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) play a critical role in the diagnosis of DF and in developing treatment plans. Currently, observation is the primary therapeutic option for a biopsy-confirmed DF. Here, we present a case of a DF that was misdiagnosed as uterine fibroid before surgery. CASE REPORT: A 36-year-old woman presented with urinary frequency and a palpable lower abdominal mass, which was suspected as uterine fibroid based on sonography and CT. During surgery, an abdominal wall mass was found to be densely adherent to the bladder. Permanent pathology revealed that the tumor was desmoid-type fibromatosis. CONCLUSION: Desmoid tumors often occur in the abdomen, abdominal wall, extremities, head, and neck. Abdominal wall DF involving the rectus abdominis muscles is most commonly observed. Conversely, desmoid tumors involving the bladder are less described. The review of similar cases reported since 1985 showed that partial cystectomy was primarily performed for complete resection.

Study of urinary mercapturic acids as biomarkers of human acrylonitrile exposure.

Exposure to the vinyl monomer acrylonitrile (AN) is primarily occupational. AN is also found in cigarette smoke. AN can be detoxified to form N-acetyl-S-(2-cyanoethyl)-cysteine (CEMA) or activated to 2-cyanoethylene oxide (CEO) and detoxified to form N-acetyl-S-(1-cyano-2-hydroxyethyl)-cysteine (CHEMA) and N-acetyl-S-(2-hydroxyethyl)-cysteine (HEMA). These urinary mercapturic acids (MAs) are considered to be potential biomarkers of AN exposure. This study assessed personal AN exposure, urinary MAs (CEMA, CHEMA, and HEMA), and cotinine (a biomarker of cigarette smoke) in 80 AN-exposed and 23 non-exposed factory workers from urine samples provided before and after work shifts. Unambiguous linear correlations were observed between levels of urinary CEMA and CHEMA with personal AN exposures, indicating their potential as chemically-specific biomarkers for AN exposures. AN exposure was the dominant factor in MA formation for AN-exposed workers, whereas urinary cotinine used as a biomarker showed that cigarette smoke exposure was the primary factor for non-exposed workers. The CHEMA/CEMA and (CHEMA+HEMA)/CEMA ratios in this human study differ from those in similar studies of AN-treated rats and mice in literature, suggesting a possible dose- and species-dependent effect in AN metabolic activation and detoxification.

Arbuscular mycorrhizal fungal communities in soils where astragalus had grown for 2 years were similar to those in the abandoned farmland.

Purpose: Astragalus-cultivated soils are enriched in arbuscular mycorrhizal fungi (AMF); however, the community changes of AMF between years in stragalus-cultivated soils are still unclear. Methods: To illustrate this, using high-throughput amplicon sequencing and quantitative real-time PCR, we analyzed the AMF communities of the abandoned farmlands and interannual astragalus-cultivated soils for 1-, 2-, 3-, and 4-years, including community composition, dominant, core, specific and significantly fluctuating AMF, co-occurrence network, alpha diversity, and beta diversity. Results: A total of 74 OTUs were classified into one phylum, Glomeromycota; one class, Glomeromycetes; four orders; four families; and six genera. The 2-year soil had the highest number of reads among the interannual soils. Only one OTU was shared among all interannual soils. The treatments significantly affected the Ace, Shannoneven, and Shannon estimators of the communities. The 2-year soil had the highest richness, evenness, and diversity among all interannual soils and was the closest to the abandoned farmland in terms of alpha diversity. Glomus of the family Glomeraceae was the dominant genus present in all treatments, and the composition of the dominant genus in interannual soils was different. Both Glomus and Diversispora were the core AMF in interannual soils, and specific AMF existed in different interannual soils. Glomus is a genus that exhibits significant interannual variation. The interannual time significantly affected the network connectivity. The results of the principal coordinate analysis showed that the community composition of the interannual soils was close to each other and separated from the abandoned farmland, and that the interannual time significantly affected the community composition. Conclusion: Among the interannual soils, the 2-year soil may be more suitable for A. sinensis seedling rotation.

An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy.

Background: This study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC). Methods: A cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in different EGFR mutant subtype by using TCGA data. Results: HLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. EGFR L858R (22.61%) was the most prevalent gene variant. The binding affinity (IC50 MT = 22.9 nM) and shared frequency (2.93%) of EGFR L858R in combination with HLA-A*33:03 were optimal. In a subsequent further analysis on immunological features of EGFR mutant subtypes, 63.1% HLA loss of heterozygosity LOH (HLA LOH) and 0.37% (7 of 1862) B2M aberrations were found in our population, both had no significant association with EGFR mutant subtypes suggesting that the process of antigen presentation involved HLA LOH and B2M mechanisms in EGFR L858R is working. Tumor mutation burden (TMB) was investigated by utilizing our panel and showed that EGFR L858R had the lowest TMB compared with other EGFR mutant subtypes. In addition, analysis of 22 immune cell types from The Cancer Genome Atlas (TCGA) data showed EGFR L858R was correlated with low level of CD8 T cells, activated CD4 memory T cells and elevated level of macrophage M2 suggesting an inhibited tumor microenvironment (TME). Conclusion: Our study identified that EGFR L858R neoantigen had the potential to generate cancer vaccines in NSCLC patients with HLA A*33:03. The neoantigen-based vaccines may become an effective salvage regimen for EGFR L858R subgroup after targeted therapy or immune checkpoint inhibitors (ICIs) failure.

Design of a Multi-Sensor System for Exploring the Relation between Finger Spasticity and Voluntary Movement in Patients with Stroke.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.

Expression of miR-92a is associated with the prognosis in non-small cell lung cancer: An observation study.

With the development of molecular biology technology, the discovery of microRNAs (miRNAs) has provided new ideas for the diagnosis, treatment, and prognosis of lung cancer and laid a foundation for the study of this malignancy. To assess the potential prognostic value of miR-92a as a new biomarker in non-small cell lung cancer (NSCLC) via clinical evaluation, a total of 100 patients with NSCLC admitted to the Respiratory and Intensive Care Department of Suining Central Hospital in Sichuan Province between August 2007 and April 2020 were retrospectively analyzed. The correlation between miR-92a expression and prognosis of patients with NSCLC was also evaluated in the present study. The expression level of miR-92a was measured by PT-PCR and in situ hybridization. Chi-square test was adopted to explore the relationship of miR-92a expression and clinical features. Kaplan-Meier survival curves were plotted to delineate the overall survival rate of patients with NSCLC. Cox regression analysis was performed to evaluate the prognostic significance of miR-92a expression in NSCLC. The miR-92a expression in NSCLC tissue samples was significantly higher than that in normal lung tissues (P < .001) and significantly correlated with the Eastern Cooperative Oncology Group score, histological type, and distant metastasis (P < .05). Survival curve revealed that patients with NSCLC and high miR-92a expression had relatively higher mortality than those with low PAK4 expression (P = .001). Cox regression analysis explained that miR-92a expression was associated with the prognosis of patients with NSCLC (HR = 1.8, 95% CI: 1.0-3.2, P = .036). In summary, miR-92a was highly expressed in NSCLC tissues and could act as a prognostic factor for patients with NSCLC. These results illustrate that miR-92a expression plays an important role in the invasion and metastasis of NSCLC, and miR-92a can be used as a new biomarker to determine the prognosis of this cancer.

Effect of Muller's muscle-conjunctival resection on the upper eyelid crease position in Asian eyelids: a retrospective cohort study.

PURPOSE: Investigating the effect of Muller's muscle-conjunctival resection (MMCR) on the eyelid crease position. METHODS: This retrospective study included patients with unilateral acquired blepharoptosis who underwent MMCR during October 2018-December 2021. The following factors were recorded: preoperative, after phenylephrine, postoperative marginal reflex distance1 (MRD1) and tarsal platform show (TPS) of bilateral eyelids. The primary outcome was to measure the change in TPS and evaluate the factors associated with post-operative TPS. The secondary outcomes included exploring the rate of MRD1 and TPS symmetry after the operation. RESULTS: Forty patients were included in the final analysis. The mean MRD1 of the ptotic eye was 1.28 ± 0.78 mm, 2.79 ± 0.66 mm and 3.20 ± 0.67 mm before, after phenylephrine and after the operation, respectively. The mean TPS of the ptotic eye was 5.90 ± 1.86 mm, 3.96 ± 1.49 mm and 2.79 ± 1.63 mm before, after phenylephrine and after the operation, respectively. Changes in mean TPS after the phenylephrine test and post-operation were statistically significant (p < 0.001). The linear regression model revealed that the absolute change in TPS after phenylephrine drop and absolute change in MRD1 post-operation were significantly correlated with the absolute change in TPS post-operation. Besides, the ratio of symmetry in MRD1 and TPS was greatly improved post-operation (82.5% and 70.0% respectively). CONCLUSION: MMCR is an effective surgical method for ptosis correction as it can not only correct the eyelid crease position but also narrow the wide TPS. This method is particularly beneficial to patients with both mild to moderate ptosis and an asymmetric crease height.

Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer.

ABSRACT: Neoantigens are ideal targets for dendritic cell (DC) vaccines. So far, only a few neoantigen-based DC vaccines have been investigated in clinical trials. Here, we reported a case of a patient with metastatic gastric cancer who received personalized neoantigen-loaded monocyte-derived dendritic cell (Neo-MoDC) vaccines followed by combination therapy of the Neo-MoDC and immune checkpoint inhibitor (ICI). The patient developed T cell responses against neoantigens after receiving the Neo-MoDC vaccine alone. The following combination therapy triggered a stronger immune response and mediated complete regression of all tumors for over 25 months till October, 2021. Peripheral blood mononuclear cells recognized seven of the eight vaccine neoantigens. And the frequency of neoantigen-specific T cell clones increased obviously after vaccination. Overall, this report describing a complete tumor regression in a gastric cancer patient mediated by Neo-MoDC vaccine in combination with ICI, and suggesting a promising treatment for patients with metastatic gastric cancer.

Development and Validation of Benzophenone Derivatives in Packaged Cereal-Based Foods by Solid-Liquid Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

We established and validated a sensitive multi-residue analytical method for identifying benzophenone (BP) and nine BP derivatives (2,4-dihydroxybenzophenone [BP-1], 2,2',4,4'-tetrahydroxydroxybenzophenone, 2-hydroxy-4-methoxy benzophenone, 2,2'-dihydroxy 4-methoxy benzophenone, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl). Solid−liquid extraction pretreatment and ultra-high-performance liquid chromatography−tandem mass spectrometry (UHPLC−MS/MS) were employed in an analysis of 85 packaged cereal-based food samples (25 pastry, 50 rice, and 10 noodle samples). The method had satisfactory linearity (R2 ≥ 0.995), low limits of detection (pastry: 0.02−4.2 ng/g; rice and noodle: 0.02−2 ng/g), and favorable precision, with within-run and between-run coefficient of variation ranges of 1−29% and 1−28%, respectively. BP and 4-MBP were detected in 100% of the pastry samples, and BP-1 and 2-OHBP were found in 76% and 56% of the pastry samples, respectively. BP and 2-OHBP were found in 92% and 38% of the rice samples, respectively. BP was found in 50% of the noodle samples. BP contributed the most to the total level of BPs in pastries, with significantly higher mean ± standard deviation (range) levels for pastries (26.8 ± 32.6 [1.8−115.4] ng/g) than rice (1.2 ± 2.0 [0.4−13.4] ng/g) and noodles (0.7 ± 0.7 [0.4−1.9] ng/g); p < 0.0001). The trace levels of 4-MBP identified in the samples demonstrate the need for the development of analytical methods with high sensitivity and specificity; the proposed method satisfies this need.

Determining the trace-level photoinitiators in juices and milk from various types of packages in Taiwan by a micro-QuEChERS-based UPLC-MS/MS.

The distribution of 16 photoinitiators (PIs)-benzophenone (BP) and its five derivatives, 4-methylbenzophenone (4-MBP), methyl-2-benzoylbenzoate (M2BB), 2-ethylhexyl-4-dimethylaminobenzoate (EHDAB), and the other 7 PIs-in packaged juice and milk was assessed using an UPLC-MS/MS with micro-QuEChERS. The validated method demonstrated robust linearity (≥0.9908), LOQs (juice: 0.006-7.26 ng/mL; milk: 0.004-7.14 ng/mL), intra- and inter-day accuracy (93.1%-110.1% for juice and 66.8%-114.6% for milk with relative standard deviations (RSDs) of ≤16.8%), and matrix effect with RSDs of ≤14.8%. BP exceeded the LOQ in 100% of 136 packaged juice (14.22 ± 7.60 ng/mL) and 51 milk (8.45 ± 3.25 ng/mL) samples, and the quantitation rates for M2BB and EHDAB in packaged juice were 100%. Notably, the 4-MBP in both juice and milk was significantly related to the packaging material. The method has been successfully applied to evaluate the occurrence and distribution of PIs in packaged juice and milk.

Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study.

This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995−2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemo-response independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. A PFI of <7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.

Identification of Benzophenone Analogs in Rice Cereal through Fast Pesticide Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

A fast, robust, and sensitive analytical method was developed and validated for the simultaneous identification of benzophenone (BP) and nine BP analogs (BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl) in 25 samples of rice cereal. Fast pesticide extraction (FaPEx) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry was applied. The developed method exhibited satisfactory linearity (r > 0.997), favorable recoveries between 71% and 119%, and a limit of detection ranging from 0.001 to 0.5 ng/g. The detection frequencies of BP, 4-MBP, and BP-3 were 100%, 88%, and 52%, respectively. BP had higher geometric levels, with a mean of 39.8 (19.1-108.9) ng/g, and 4-MBP had low levels, with a mean of 1.9 (1.3-3.3) ng/g. The method can be applied to routine rice cereal analysis at the nanogram-per-gram level. For infants aged 0-3 years, the hazard quotients of BP and 4-MBP were lower than one, and the margin of exposure for BP was higher than 10,000, suggesting that rice cereal consumption poses no health concern for Taiwanese infants.