Transcriptomics Coupled with Proteomics Reveals Osimertinib-induced Myocardial Mitochondrial Dysfunction.

Osimertinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for cancer treatment, can cause significant cardiac toxicity. However, the specific mechanism of osimertinib-induced cardiotoxicity is not fully understood. In this study, we administered osimertinib to mice and neonatal rat ventricular myocytes (NRVMs). We observed significant structural and functional damage to the hearts of these mice, along with a marked increase in cardiac injury biomarkers and accompanying ultrastructural damage to mitochondria. We integrated 4D label-free protein quantification and RNA-Seq methods to analyze the sequencing data of NRVMs under osimertinib treatment (0 and 2.5µM). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis evidenced that differentially expressed genes (DEGs)and differentially expressed proteins (DEPs) were distinctly enriched for oxidative phosphorylation (OXPHOs). Simultaneously, osimertinib primarily affected the contents of adenosine triphosphate (ATP). Further investigations revealed that osimertinib disrupts the functions of the ATP synthase (complex V), leading to a reduction in ATP production. Taken together, our data demonstrated that osimertinib causes mitochondrial dysfunction, which in turn leads to the onset of cardiac toxicity.

Postoperative Lenvatinib plus PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with MVI (BCLC 0-A): A Propensity Score Matching Analysis.

PURPOSE: This research seeks to determine the effectiveness of post-operative adjuvant lenvatinib plus PD-1 blockade for early-stage HCC patients with microvascular invasion (MVI). METHODS: 393 HCC patients (Barcelona Clinic Liver Cancer stage 0-A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to inclusion and exclusion criteria and assigned to two groups: surgery alone (Surgery-alone) and surgery with lenvatinib and PD-1 blockade (Surgery+Len+PD-1) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate following the application of propensity score matching (PSM). The Cox proportional hazards model was utilized for univariate and multivariate analysis. RESULTS: 99 matched pairs were selected using PSM. Patients in the Surgery+Len+PD-1 group had significantly higher three-year RFS (76.8%, 65.7%, and 53.5%) compared to patients in the Surgery-alone group (60.6%, 45.5%, and 37.4%) (P=0.012). The two groups showed no significant differences in recurrence types and OS. Surgery-alone, MVI-M2, and AFP≥200ng/mL were independent risk factors for RFS (P<0.05), and history of alcoholism was an independent risk factor for OS (P=0.022). CONCLUSIONS: Postoperative lenvatinib plus PD-1 blockade improved the RFS in HCC patients with MVI and was particularly beneficial for specific individuals.

Behavioural and neuropsychological outcomes in children exposed in utero to maternal labour epidural analgesia.

BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.

Casein hydrolysate in naturally-fermented buckwheat sourdough: Effects on fermented and physicochemical characteristics, texture, and bacterial microbial composition.

The effect of a casein hydrolysate (CH) on the fermentation and quality of a naturally-fermented buckwheat sourdough (NFBS) were investigated, through assessing the fermentation characteristics, carbohydrate and protein degradation, texture, and bacterial composition of NFBS. According to the assaying data, CH might both increase the amount of lactic acid bacteria by 2.62 % and shorten the fermentation period by at least 3 h, subsequently leading to enhanced degradation of carbohydrate and protein, accompanied by a softer texture. More importantly, CH increased the relative abundance of lactobacillus in NFBS, making it the dominant bacterial genus and inhibited the growth of spoilage bacteria. In addition, Spearman correlation analysis indicated that the pH value, lactic and acetic acid contents, carbohydrates, protease activity, and these textural indices like hardness, elasticity, and adhesion had a positive/negative correlation with the bacterial composition of NFBS (Spearman correlation coefficient: -0.93-0.95). CH was thus regarded to be helpful to NFBS processing and production mainly by shortening its fermentation time, improving its fermentation performance, causing a finer texture and microstructure, and changing bacterial composition.

Graphene oxide/ε-poly-L-lysine self-assembled functionalized coatings improve the biocompatibility and antibacterial properties of titanium implants.

The construction of an antibacterial biological coating on titanium surface plays an important role in the long-term stability of oral implant restoration. Graphene oxide (GO) has been widely studied because of its excellent antibacterial properties and osteogenic activity. However, striking a balance between its biological toxicity and antibacterial properties remains a significant challenge with GO. ε-poly-L-lysine (PLL) has broad-spectrum antibacterial activity and ultra-high safety performance. Using Layer-by-layer self-assembly technology (LBL), different layers of PLL/GO coatings and GO self-assembly coatings were assembled on the surface of titanium sheet. The materials were characterized using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle test. The antibacterial properties of Porphyromonas gingivalis (P.g.) were analyzed through SEM, coated plate experiment, and inhibition zone experiment. CCK-8 was used to determine the cytotoxicity of the material to MC3T3 cells, and zebrafish larvae and embryos were used to determine the developmental toxicity and inflammatory effects of the material. The results show that the combined assembly of 20 layers of GO and PLL exhibits good antibacterial properties and no biological toxicity, suggesting a potential application for a titanium-based implant modification scheme.

Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy. METHODS: We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993. FINDINGS: A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces). INTERPRETATION: Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions. FUNDING: Nanjing Medical University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

PD-1/PD-L1 axis induced host immunosuppression via PI3K/Akt/mTOR signalling pathway in piglets infected by Glaesserella Parasuis.

Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer's disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 108 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+ cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA.

Repetitive transcranial magnetic stimulation ameliorates cognitive deficits in mice with radiation-induced brain injury by attenuating microglial pyroptosis and promoting neurogenesis via BDNF pathway.

BACKGROUND: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood. METHODS: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus. RESULTS: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1ß were upregulated. CONCLUSION: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.

Discrimination and quantification of volatile compounds in beer by FTIR combined with machine learning approaches.

The composition of volatile compounds in beer is crucial to the quality of beer. Herein, we identified 23 volatile compounds, namely, 12 esters, 4 alcohols, 5 acids, and 2 phenols, in nine different beer types using GC-MS. By performing PCA of the data of the flavor compounds, the different beer types were well discriminated. Ethyl caproate, ethyl caprylate, and phenylethyl alcohol were identified as the crucial volatile compounds to discriminate different beers. PLS regression analysis was performed to model and predict the contents of six crucial volatile compounds in the beer samples based on the characteristic wavelength of the FTIR spectrum. The R2 value of each sample in the prediction model was 0.9398-0.9994, and RMSEP was 0.0122-0.7011. The method proposed in this paper has been applied to determine flavor compounds in beer samples with good consistency compared with GC-MS.

Thoracic spine infection caused by Pseudomonas fluorescens: A case report and review of literature.

BACKGROUND: The clinical incidence of spinal infection is gradually increasing, and its onset is insidious, easily leading to missed diagnosis and misdiagnosis, which may lead to serious complications such as nervous system dysfunction, spinal instability and/or deformity, and cause a huge burden on society and families. Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients. At present, the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus, Streptococcus, Pneumococcus, Escherichia coli, and Klebsiella. There are no reports of spinal infection caused by Pseudomonas fluorescens. CASE SUMMARY: We report a 32-year-old female patient with spinal infection. She presented with flank pain, initially thought to be bone metastases or bone tuberculosis, and had a family background of tumors. Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection. Histopathology of the lesion showed inflammation, tissue culture of the lesion was negative several times, and the possible pathogen - Pseudomonas fluorescens was found after gene sequencing of the lesion. The patient recovered completely after a full course of antibiotic treatment. CONCLUSION: This report increases the range of pathogens involved in spinal infections, highlights the unique advantages of gene sequencing technology in difficult-to-diagnose diseases, and validates conservative treatment with a full course of antibiotics for spinal infections without complications.

GNAI3 mediated by Lin28A regulates lipopolysaccharide-induced inflammation and osteogenic differentiation in periodontal stem cells by mediating the NF-κB/NLRP3 inflammasome pathway.

OBJECTIVES: The aim of this study was to investigate the regulatory role of G protein subunit alpha i3 (GNAI3) in periodontitis. DESIGN: Following the induction of human periodontal ligament stem cells (hPDLSCs) with lipopolysaccharide (LPS), the mRNA and protein expressions of GNAI3 and Lin28A were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. The transfection efficiency of Oe-GNAI3 and sh-Lin28A was examined by virtue of RT-qPCR and western blot. With the application of ELISA and flow cytometry, the releases of inflammatory cytokines and cell apoptosis were appraised. Alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining were conducted to evaluate osteogenic differentiation. Next, the binding ability of Lin28A with GNAI3 mRNA was estimated by radioimmunoprecipitation (RIP) assay while the stability of GNAI3 mRNA was assessed utilizing RT-qPCR. Western blot was employed for the measurement of inflammation-, apoptosis- and nuclear factor-kappaB (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway-related proteins and osteogenic markers. RESULTS: The expression of GNAI3 was down-regulated in LPS-induced hPDLSCs. After the transfection with Oe-GNAI3, the inflammation and apoptosis in LPS-induced hPDLSCs were inhibited while osteogenic differentiation was promoted. Moreover, Lin28A could stabilize GNAI3 mRNA and Lin28A knockdown significantly reduced GNAI3 expression. Further experiments verified that the inhibitory effects of GNAI3 overexpression on LPS-induced cellular inflammation and cell apoptosis as well as the promotive effects on osteogenic differentiation in hPDLSCs were all partially counteracted by Lin28A depletion, which may possibly be mediated via the regulation of the NF-κB/NLRP3 inflammasome pathway. CONCLUSION: GNAI3 that mediated by Lin28A regulates the inflammation and osteogenic differentiation in LPS-induced hPDLSCs by mediating the NF-κB/NLRP3 inflammasome pathway.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Variants in CLCN1 and PDE4C Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs.

(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical signs in four young French bulldogs via muscle histopathology coupled with whole genome and Sanger sequencing. (2) Methods: Dogs were evaluated by veterinary clinical internists and neurologists, and biopsies were obtained for histopathological diagnosis. DNA was submitted for whole genome sequencing, followed by bioinformatics evaluation and confirmation of variants via Sanger sequencing in two cases. (3) Results: Two novel variants were identified. The first, found in two related French bulldogs, was a homozygous variant in the chloride channel gene CLCN1 known to cause non-dystrophic congenital myotonia, and the second, found in an unrelated French bulldog, was a heterozygous variant in the cAMP phosphodiesterase gene PDE4C, which is the major phosphodiesterase expressed in skeletal muscle and may play a role in decreasing muscle atrophy. An underlying molecular basis in one other case has not yet been identified. (4) Conclusions: Here, we identified two novel variants, one in the CLCN1 and one in the PDE4C gene, associated with clinical signs of muscle hypertrophy, dysphagia, and gait abnormalities, and we suggested other bases of these phenotypes in French bulldogs that are yet to be discovered. Identification of genes and deleterious variants associated with these clinical signs may assist breeders in improving the overall health of this very popular breed and may lead to the identification of new therapies to reverse muscle atrophy in people and animals with neuromuscular diseases.

Novel biomarkers related to oxidative stress and immunity in chronic kidney disease.

Introduction: The incidence of chronic kidney disease (CKD) has been increasing in recent years, gradually becoming a global health crisis. Due to limited treatment options, novel molecular pathways are urgently required to advance the treatment and diagnosis of CKD. Materials and methods: The characteristics of differentially expressed genes (DEGs) in CKD patients were analyzed using Gene Expression Omnibus (GEO) database, and genes related to oxidative stress were retrieved from the Genecard database. Subsequently, a comprehensive approach was applied, including immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis, to identify hub genes among differentially expressed immune-related oxidative stress genes (DEIOSGs). Validation of hub genes was performed using an external data set, and diagnostic potential capability was evaluated through receiver operating curve (ROC) analysis. In animal experiments, the expression of hub genes in CKD was confirmed by inducing a CKD model through a 5/6 nephrectomy procedure. Finally, the relationship between these hub genes and clinical characteristics were assessed using the Nephroseq v5 database. Results: 29 DEIOSGs were identified by comprehensive bioinformatics analysis. PPI analysis screened the hub genes NCF2, S100A9, and SELL. ROC analysis demonstrated excellent diagnostic efficacy. Further validation from other databases and animal experiments confirmed a substantial upregulation in the expression of hub genes in CKD. Additionally, clinical correlation analysis established a clear link between hub gene expression and renal function deterioration. Conclusions: Our study confirms NCF2, S100A9, and SELL as diagnostic biomarkers associated with immune response and oxidative stress in CKD, suggesting their potential as novel targets for CKD diagnosis and treatment.

Gender differences in geriatric depressive symptoms in urban China: the role of ADL and sensory and communication abilities.

Objectives: ADL and Sensory and Communication Abilities are important indicators of the quality of life of the elderly which are significant determinants of health, particularly in developing countries. The present cross-sectional study investigated effect of ADL and Sensory and Communication Abilities on depressive symptoms, as well as the the role of gender in these effects. Design: This is a cross-sectional study. Setting: A nationally representative cross-sectional survey among the Chinese population aged 60 years and over. Participants: A total of 163296 females and 148724 males aged 65 and over in 2019 in urban China. Outcome measures: Prevalence, risk factors and gender differences in geriatric depressive symptoms among urban elderly. Results: Approximately 95.69% of the participants had depressive symptoms according to the CESD-10, with no statistically significant gender difference of 52.15% in females and 47.85% in males. Logistic regression findings suggest that geriatric depressive symptoms are significantly associated with the lack of eldercare (OR=2.427, female; OR=1.426, male), living alone(OR= 1.430, female; OR= 1.179, male), ADL dysfunction (OR=1.528, female; OR=1.246, male), and impaired sensory and communication ability (OR=1.338, female; OR=1.185, male) among both female and male participants. Remarkably, geriatric depressive symptoms are only significantly associated with age (≥75, OR = 1.327), marital status (unmarried, OR=1.598), the number of children (no children, OR=2.271), and the living arrangement (living alone, OR= 1.430) among female participants. Conclusion: Significant gender differences in these associations were found for living alone, ADL dysfunction and impaired sensory and communication ability. Moreover, the study emphasized that the gender difference exists in terms of geriatric depression in urban China. Females are more likely to experience depressive than males with the same circumstances.

Mapping Spatiotemporal Heterogeneity in Multifocal Breast Tumor Progression by Noninvasive Ultrasound Elastography-Guided Mass Spectrometry Imaging Strategy.

Spatiotemporal heterogeneity of tumors provides an escape mechanism for breast cancer cells, which can obstruct the investigation of tumor progression. While molecular profiling obtained from mass spectrometry imaging (MSI) is rich in biochemical information, it lacks the capacity for in vivo analysis. Ultrasound diagnosis has a high diagnostic accuracy but low chemical specificity. Here, we describe a noninvasive ultrasound elastography (UE)-guided MSI strategy (UEg-MSI) that integrates physical and biochemical characteristics of tumors acquired from both in vivo and in vitro imaging. Using UEg-MSI, both elasticity histopathology metabolism "fingerprints" and reciprocal crosstalk are revealed, indicating the intact, multifocal spatiotemporal heterogeneity of spontaneous tumorigenesis of the breast from early, middle, and late stages. Our results demonstrate a gradual increase in malignant degree of primary focus in cervical and thoracic mammary glands. This progression is characterized by increased stiffness according to elasticity scores, histopathological changes from hyperplasia to increased nests of neoplastic cells and necrotic areas, and regional metabolic heterogeneity and reprogramming at the spatiotemporal level. De novo fatty acid (FA) synthesis focused on independent (such as ω-9 FAs) and dependent (such as ω-6 FAs) dietary FA intake in the core cancerous nest areas in the middle and late stages of tumor or in the peripheral microareas in the early stage of the tumor. SM-Cer signaling pathway and GPs biosynthesis and degradation, as well as glycerophosphoinositol intensity, changed in multiple characteristic microareas. The UEg-MSI strategy holds the potential to expand MSI applications and enhance ultrasound-mediated cancer diagnosis. It offers new insight into early cancer discovery and the occurrence of metastasis.

The impact of first-trimester subchorionic hematomas on pregnancy outcomes after euploid embryo transfer: a retrospective cohort study.

BACKGROUND: The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer. METHODS: We retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors. RESULTS: A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25-3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39-0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups. CONCLUSIONS: The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Dissolution and regeneration of starch in hydroxyl-functionalized ionic liquid aqueous solution.

There have been continuous quests for suitable solvents for starch, given the importance of effective starch dissolution in its modification and subsequent materials production. In light of this, the potential of hydroxyl-functionalized ionic liquid (IL) as a promising solvent for starch was investigated. Within this study, a hydroxyl-functionalized IL 1-(2,3-dihydroxypropyl)-3-methylimidazole chloride ([Dhpmim][Cl]) was synthesized, and the dissolution of starch in this IL and its aqueous solutions was examined. Starch (5.35 wt%) was completely dissolved in [Dhpmim][Cl] within 2 h at 100 °C. The solubility of starch in [Dhpmim][Cl]-water mixtures initially increased and then decreased with rising water content. The optimal ratio was found to be 1:9 (wt/wt) water:[Dhpmim][Cl], achieving the highest solubility at 9.28 wt%. Density functional theory (DFT) simulations elucidated the possible interactions between starch and solvents. After dissolution and regeneration in the 1:9 water:[Dhpmim][Cl] mixture, starch showed no discernible change in the molecular structure, with no derivatization reaction observed. Regenerated starch exhibited a transformation in crystalline structure from A-type to V-type, and its relative crystallinity (12.4 %) was lower than that of native starch (25.2 %), resulting in decreased thermal stability. This study suggests that the hydroxyl-functionalized IL, [Dhpmim][Cl], and its aqueous solutions serve as effective solvents for starch dissolution.

Validating the Use of Percent Grammatical Utterances for Assessing Mandarin-Speaking Children's Grammatical Skill: Evidence From 3-Year-Olds.

PURPOSE: The study examined the use of percent grammatical utterances (PGUs) for assessing grammatical skills in Mandarin-speaking 3-year-old children. METHOD: Participants were 30 Mandarin-speaking 3-year-olds with typical development. Language samples were collected in two visits for each child using a picture description task. Children were asked to talk about 16 pictures in response to questions and prompts at each visit. Pictures for the language sample collection were identical across the visits. PGUs were computed, and the grammatical errors that children produced in the task were coded and tallied for error types at each visit. Test-retest reliability, split-half reliability, and concurrent criterion validity of PGUs were evaluated. RESULTS: The mean PGU level was approximately 78% at Visit 1 and 81% at Visit 2, both of which were significantly below the mastery level (i.e., 90%). The correlation coefficient for test-retest reliability of PGU was large (r = .70, p < .01); the correlation coefficient for split-half reliability was medium at Visit 1 (r = .47, p < .01) and large (r = .65, p < .01) at Visit 2. In addition, the correlation coefficient for concurrent criterion validity of PGU was medium for both visits (rs ≥ .35, ps ≤ .03). The ranking and proportion of each error type were similar between the visits. CONCLUSION: The initial evidence from psychometric properties suggests that PGU computed from the picture description task is a reliable and valid measure for evaluating grammatical skills in Mandarin-speaking 3-year-old children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25395499.

An integrated approach to assess human health risk of neonicotinoid insecticides in surface water of the Yangtze River Basin, China.

Neonicotinoids are widely used insecticides that have raised considerable concerns for both environmental and human health. However, there lack of comprehensive evaluation of their accumulation in surface water ecosystems and exposure to various human groups. Additionally, there's a distinct lack of scientific evidence describing the carcinogenic and non-carcinogenic impacts of neonicotinoids from surface water. Using an integrated approach employing the Relative Potency Factor (RPF), Hazard Index (HI), and Monte Carlo Simulation (MCS), the study assessed neonicotinoid exposure and risk to four demographic groups via dermal contact and mistaken oral intake pathways in the Yangtze River Basin (YRB), China. Neonicotinoid concentrations range from 0.1 to 408.12 ng/L, indicating potential risk (10-3 to 10-1) across the studied demographic groups. The Incremental Lifetime Cancer Risk (ILCR) for dermal contact was within a moderate range of 2.00 × 10-3 to 1.67 × 10-2, while the mistaken oral intake was also within a moderate range of 3.07 × 10-3 to 7.05 × 10-3. The Hazard Index (HI) for dermal exposure ranged from 1.49 × 10-2 to 0.125, while for mistaken oral intake, it varied between 2.69 × 10-2 and 0.14. The findings highlight the importance of implementing specific interventions to address neonicotinoid exposure, especially among demographic groups that are more susceptible. This research underscores the urgent need for targeted strategies to address neonicotinoid risks to vulnerable populations within the YRB while contributing to insights for effective policies to mitigate neonicotinoid exposure in surface water ecosystems globally.