Adversarial training collaborating hybrid convolution-transformer network for automatic identification of reactive lymphocytes in peripheral blood.

Reactive lymphocytes may indicate diseases such as viral infections. Identifying these abnormal lymphocytes is crucial for disease diagnosis. Currently, reactive lymphocytes are mainly manually identified by pathological experts with microscopes and morphological knowledge, which is time-consuming and laborious. Some studies have used convolutional neural networks (CNNs) to identify peripheral blood leukocytes, but there are limitations in the small receptive field of the model. Our model introduces a transformer based on CNN, expands the receptive field of the model, and enables it to extract global features more efficiently. We also enhance the generalization ability of the model through virtual adversarial training (VAT) without changing the parameters of the model. Finally, our model achieves an overall accuracy of 93.66% on the test set, and the accuracy of reactive lymphocytes also reaches 88.03%. This work takes another step toward the efficient identification of reactive lymphocytes.

The impact of kaolin mining activities on bacterial diversity and community structure in the rhizosphere soil of three local plants.

Introduction: Thus far, the impact of kaolin mining activities on the surrounding native plants and rhizosphere microecology has not been fully understood. Methods: In this study, we used 16S rRNA high-throughput sequencing to examine the impact of kaolin mining on the rhizosphere bacterial communities and functions of three local plant species: Conyza bonariensis, Artemisia annua, and Dodonaea viscosa. Results: The results showed that kaolin mining significantly reduced the diversity of rhizosphere bacteria in these plants, as indicated by the Shannon, Simpson, Chao1, and observed species indices (p < 0.05). Kaolin mining had an impact on the recruitment of three rhizosphere bacteria native to the area: Actinoplanes, RB41, and Mycobacterium. These bacteria were found to be more abundant in the rhizosphere soil of three local plants than in bulk soil, yet the mining of kaolin caused a decrease in their abundance (p < 0.05). Interestingly, Ralstonia was enriched in the rhizosphere of these plants found in kaolin mining areas, suggesting its resilience to environmental stress. Furthermore, the three plants had different dominant rhizosphere bacterial populations in kaolin mining areas, such as Nocardioides, Pseudarthrobacter, and Sphingomonas, likely due to the unique microecology of the plant rhizosphere. Kaolin mining activities also caused a shift in the functional diversity of rhizosphere bacteria in the three local plants, with each plant displaying different functions to cope with kaolin mining-induced stress, such as increased abundance of the GlpM family and glucan-binding domain. Discussion: This study is the first to investigate the effects of kaolin mining on the rhizosphere microecology of local plants, thus contributing to the establishment of soil microecological health monitoring indicators to better control soil pollution in kaolin mining areas.

Influence of spatial and temporal diversity and succession of microbial communities on physicochemical properties and flavor substances of soy sauce.

In this study, the influence and relationship between the microbial structure composition at different spatial locations during soy sauce fermentation and the quality of soy sauce were investigated. Within 3-7 days of fermentation, the abundance of Chromohalobacter in the surface and upper layers of moromi was initially high but subsequently decreased. In contrast, Tetragenococcus exhibited low abundance on the surface of moromi at the beginning of fermentation but emerged as the absolute dominant bacteria by the end of the fermentation process. Throughout the fermentation period of 3-42 days, Staphylococcus and Bacillus were the predominant bacterial genera observed at the bottom of the moromi. In addition, Halanaerobium was the dominant bacterial genus in the crude soy sauce layer throughout the fermentation process. Tetragenococcus and Zygosaccharomyces were strongly positively correlated with total acid and ammonia nitrogen. Bacillus and Staphylococcus were significantly negatively correlated with the salt content.

The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients.

This study aimed to investigate the expression and clinical significance of syncytin-1 in the serum exosomes of hepatocellular carcinoma (HCC) patients. Serum samples were collected from 61 patients with newly diagnosed HCC and 61 healthy individuals. Exosomes were extracted from serum samples and identified using transmission electron microscopy and Western blot. The relative expression levels of syncytin-1 in exosomes were determined by real-time quantitative PCR. The protein expression levels of alpha-fetoprotein and syncytin-1 in HCC patients were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to evaluate the sensitivity and specificity of serum exosomal syncytin-1 in diagnosing HCC. The relationships between syncytin-1 expression and clinical pathological features were analyzed using receiver operating characteristic curve analysis. The results showed that the expression level of syncytin-1 in the serum of patients with newly diagnosed HCC was significantly higher than that in the normal control group (P < 0.0001). Using pathological diagnosis as the gold standard, the sensitivity and specificity of syncytin-1 for the auxiliary diagnosis of HCC were 91.3% and 75.5%, respectively, which were significantly higher than those of alpha-fetoprotein (P < 0.0001). The relative expression level of serum exosomal syncytin-1 was significantly associated with lymph node metastasis, degree of differentiation, and CNLC staging of HCC patients (P < 0.05). In conclusion, syncytin-1 in serum exosomes has high sensitivity and specificity for diagnosing HCC and can serve as a novel tumor marker for early screening, detection, and staging of HCC.

Disease burden and attributable risk factors of lip and oral cavity cancer in China from 1990 to 2021 and its prediction to 2031.

Aims: This study addresses the essential need for updated information on the burden of lip and oral cavity cancer (LOC) in China for informed healthcare planning. We aim to estimate the temporal trends and the attributable burdens of selected risk factors of LOC in China (1990-2021), and to predict the possible trends (2022-2031). Subject and methods: Analysis was conducted using data from the Global Burden of Disease study (GBD) 2021, encompassing six key metrics: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute number and age-standardized rates, alongside 95% uncertainty intervals, were computed. Forecasting of disease burden from 2022 to 2031 was performed using an autoregressive integrated moving average (ARIMA) model. Results: Over the observed period (1990-2021), there were notable increases in the number of deaths (142.2%), incidence (283.7%), prevalence (438.0%), DALYs (109.2%), YLDs (341.2%), and YLLs (105.1%). Age-standardized rates demonstrated notable changes, showing decreases and increases of -5.8, 57.3, 143.7, -8.9%, 85.8%, and - 10.7% in the respective metrics. The substantial majority of LOC burden was observed among individuals aged 40-79 years, and LOC may exhibit a higher burden among males in China. From 2022 to 2031, the age-standardized rate of incidence, prevalence, and YLDs of LOC showed upward trends; while mortality, DALYs, and YLLs showed downward trends, and their estimated values were predicted to change to 2.72, 10.47, 1.11, 1.10, 28.52, and 27.43 per 100,000 in 2031, respectively. Notably, tobacco and high alcohol use emerged as predominant risk factors contributing to the burden of LOC. Conclusion: Between 1990 and 2021, the disability burden from LOC in China increased, while the death burden decreased, and projections suggest these trends will persist over the next decade. A significant portion of this disease burden to modifiable risk factors, specifically tobacco use and excessive alcohol consumption, predominantly affecting males and individuals aged 40-79 years. Attention to these areas is essential for implementing targeted interventions and reducing the impact of LOC in China.

The role of RRS1 in breast cancer cells metastasis and AEG-1/AKT/c-Myc signaling pathway.

Breast cancer is the most common malignant tumor in women. Recurrence, metastasis, and chemotherapy resistance are the main causes of death in breast cancer patients. The inhibition of breast cancer metastasis is of great significance for prolonging its survival. Ribosome biogenesis regulatory protein homolog (RRS1) is overexpressed in breast cancer tissues and is involved in regulating the carcinogenic process of breast cancer cells. However, the exact signaling pathway and molecular mechanism of RRS1 promoting breast cancer metastasis are not fully understood. Hence, the primary objective of our study is to investigate the correlation between RRS1 and breast cancer metastasis. Bioinformatic analysis was used to identify the expression levels and prognostic significance of RRS1 in breast cancer. Lenti-sh RRS1 lentivirus was constructed and employed to downregulate the RRS1 expression in MDA-MB-231 and BT549 cells, which had a high-level expression of RRS1. Subsequently, we assessed the impact of RRS1 downregulation on the proliferation, migration, and invasion of breast cancer cells using CCK-8, apoptosis, and cell cycle by flow cytometry, wound healing test, Transwell migration, and invasion experiments. Moreover, we utilized an in vivo imaging system to examine the metastatic potential of breast cancer cells after RRS1 knockdown. Picrate staining and hematoxylin-eosin staining were employed to evaluate the presence of metastatic lesions. To gain a deeper understanding of the molecular mechanism, we conducted co-immunoprecipitation and western blot. The significant overexpression of RRS1 in breast cancer indicates a worse prognosis, as determined through TCGA databases (p<0.01). Additionally, RRS1 exhibits upregulation in breast cancer (p<0.001), which is tightly linked to the occurrence of lymph node metastasis (p<0.001). Clinical breast cancer tissues and breast cancer cell lines also demonstrated a noteworthy upregulation of RRS1 (p<0.05). Loss-of-function experiment illustrated that the inhibiting of RRS1 expression reduced the rapid proliferation capacity of MDA-MB-231 and BT549 cells and hindered their migration and invasion capabilities (p<0.05). Importantly, the suppression of RRS1 significantly diminished lung metastasis in Balb/c nude mice that were injected with MDA-MB-231 cells (p<0.01). Mechanistically, RRS1 may interact with the AEG-1 to modulate the phosphorylation of AKT at T308 and S473, consequently impeding the activity of c-Myc (p<0.05). To conclude, RRS1 functions as a potential oncogene in breast cancer by leveraging the AEG-1/AKT/c-Myc signaling.

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015-2020).

AIMS: To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US. MATERIALS AND METHODS: This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates. RESULTS: A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1-Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676-$24,597]) in 1 L, $30,027 ($20,868 [$13,416-$31,016]) in 2 L, and $47,064 ($25,689 [$15,555-$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1-Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534-$253,630]) and $28,466 ($23,696 [$15,466-$39,107]), respectively. CONCLUSIONS: No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

Instrumented timed up and go test and machine learning-based levodopa response evaluation: a pilot study.

BACKGROUND: The acute levodopa challenge test (ALCT) is a universal method for evaluating levodopa response (LR). Assessment of Movement Disorder Society's Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) is a key step in ALCT, which is some extent subjective and inconvenience. METHODS: This study developed a machine learning method based on instrumented Timed Up and Go (iTUG) test to evaluate the patients' response to levodopa and compared it with classic ALCT. Forty-two patients with parkinsonism were recruited and administered with levodopa. MDS-UPDRS III and the iTUG were conducted in both OFF-and ON-medication state. Kinematic parameters, signal time and frequency domain features were extracted from sensor data. Two XGBoost models, levodopa response regression (LRR) model and motor symptom evaluation (MSE) model, were trained to predict the levodopa response (LR) of the patients using leave-one-subject-out cross-validation. RESULTS: The LR predicted by the LRR model agreed with that calculated by the classic ALCT (ICC = 0.95). When the LRR model was used to detect patients with a positive LR, the positive predictive value was 0.94. CONCLUSIONS: Machine learning based on wearable sensor data and the iTUG test may be effective and comprehensive for evaluating LR and predicting the benefit of dopaminergic therapy.

Iodophor-catalyzed sulfenylation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles.

An iodophor-catalyzed sulfenylation of indoles using sulfonyl hydrazides as sulfur source to synthesize 3-sulfenylindoles in aqueous phase has been achieved. Notably, iodophor as catalyst and solvent is inexpensive, commercially available and no innocuous to the environment. The method is also easy to operate. Moreover, the synthetic strategy features a wide range of substrates with excellent tolerance to diverse functional groups. A plausible mechanism for the iodophor-mediated 3-sulfenylation of indoles with sulfonyl hydrazides has been proposed. In addition, 3-(phenylthio)-1H-indole was obtained on a multi-gram scale.

Characterization and phylogenetic analysis of the Talaromyces liani (kamyschko) Yilmaz, Frisvad & Samson, 2014 (Eurotiales: trichocomaceae) mitochondrial genome.

The filamentous fungus Talaromyces liani (Kamyschko) Yilmaz, Frisvad & Samson, 2014, has attracted considerable interest in biotechnology due to its diverse industrial applications and physiological characteristics. However, the mitochondrial genome of T. liani remains uncharacterized. Here, we present the complete mitochondrial genome of T. liani, comprising 38,000 bp with a GC content of 24.61%. This genome includes 15 core protein-coding genes, 4 independent ORFs, 6 intronic ORFs, 26 tRNAs, and 2 rRNA genes. Phylogenetic analysis using Bayesian inference (BI) revealed the evolutionary relationships among 15 fungi from Eurotiales, strongly supporting distinct clades and indicating that T. liani most closely related to T. pinophilus.

Anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis with liver dysfunction: a warning sign of higher death risk.

This study aimed to investigate and analyze the clinical and immunological features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis (MDA5 + DM) complicated with clinical liver dysfunction. A cohort of 85 patients diagnosed with MDA5 + DM admitted into Peking University People's Hospital from 2006 to 2023 were retrospectively enrolled in this study. Clinical characteristics and survival status were collected and analyzed. Clinical liver dysfunction occurred in 28% (24/85) of MDA5 + DM patients. Patients with clinical liver dysfunction were more likely to have muscle impairment (83.3% vs. 52.5%, P = 0.009) and rapidly progressive ILD (72.7% vs. 47.4%, P = 0.027). Lactate dehydrogenase (LDH) (378.5 (296.0,453.8) U/L vs. 280.0 (218.0,355.0) U/L, P = 0.002) and ferritin (FER) (883.0 (279.8,2100.5) ng/mL vs. 293.5.0 (84.0,862.7) ng/mL, P = 0.040) were significantly elevated and total numbers of lymphocytes (827.2 ± 517.2 /µL vs. 1301.8 ± 720.9 /µL, P = 0.042), and CD4 + T cells (403.8 ± 315.9 /µL vs. 548.6 ± 257.7 /µL, P = 0.045) were significantly decreased in patients with clinical liver function. Muscle weakness (OR 5.184, 95% CI 1.305, 20.595, P = 0.019) was identified as an independent risk factor for clinical liver dysfunction. Clinical liver dysfunction was identified as an independent risk factor for poor prognosis in patients with MDA5 + DM (HR = 4.030, 95% Cl 1.233, 13.176, P = 0.021), with an 18-month survival rate of 69%. Liver dysfunction is one of the extramuscular manifestations in patients with MDA5 + DM and might be associated with a poor prognosis.

Recombinant collagen for the repair of skin wounds and photo-aging damage.

The skin, being the body's primary defense mechanism, is susceptible to various injuries such as epidermal wounds, natural aging, and ultraviolet-induced damage. As a result, there is growing interest in researching skin repair methods. Traditional animal-derived collagen, widely available on the market, poses risks due to its immunogenicity and potential for viral contamination. In contrast, recombinant collagen sourced from human genes offers a safer alternative. To investigate the potential of human recombinant collagen in skin repair, our research team applied two types, type I human collagen (Col I) and CF-1552(I), to two different skin injury models: a wound-healing model and a photo-aging model. Our findings indicate that both Col I and CF-1552(I) effectively enhance wound healing and repair skin damaged by ultraviolet exposure. Notably, CF-1552(I) showed effects comparable to Col I in promoting cell proliferation in the wound-healing model and increasing malondialdehyde content in the photo-aging model, suggesting that CF-1552(I) may offer greater potential for skin repair compared to the larger Col I molecule.

Association of MORC2 expression with progression-free survival in cervical cancer patients treated with concurrent chemoradiotherapy.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.

Metastatic Lung Adenocarcinoma Diagnosed by Thyroid Biopsy: A Case Report.

Lung cancer metastasis to the thyroid gland is a rare occurrence. We report a rare presentation of metastatic lung adenocarcinoma diagnosed by thyroid biopsy during a tracheostomy in a 35-year-old female. A 35-year-old female with a history of epilepsy, hypothyroidism, and 15-pack-year smoking presented with four months of increasing neck swelling. The patient reported no airway symptoms upon admission. Initial flexible laryngoscopy revealed supraglottic edema. Workup including CT neck and chest revealed diffuse bilateral cervical lymphadenopathy, diffusely enlarged thyroid gland without any nodules or masses, and mediastinal lymphadenopathy with no obvious lung masses or nodules. Excisional right axillary nodal biopsy as well as right supraclavicular biopsy showed metastatic carcinoma with an equivocal staining pattern favoring lung adenocarcinoma versus thyroid carcinoma. During inpatient admission, the patient began having increasing dyspnea with flexible laryngoscopy revealing worsening supraglottic mucosal edema. The patient subsequently underwent tracheostomy with excisional thyroid biopsy due to concern for malignancy. Intraoperatively, the strap muscles were found to be firmly adhered to the underlying thyroid gland. Dissection of the thyroid isthmus revealed thickened tissue. The final pathology of the thyroid biopsy revealed metastatic adenocarcinoma, consistent with lung primary. It is important to keep in mind that, although rare, the thyroid gland may be a site of metastasis for primary lung adenocarcinoma. Prompt recognition and understanding of this possible event are key to achieving adequate disease control.

Clinical profiles of Mycoplasma pneumoniae pneumonia in children with different pleural effusion patterns: a retrospective study.

BACKGROUND: The clinical significance of the presence or absence of Mycoplasma pneumoniae (MP) in pleural effusion in Mycoplasma pneumoniae pneumonia (MPP) children has not yet been elucidated. Herein, we investigated the clinical implication of pleural fluid MP positive in children with MPP. METHODS: A total of 165 MPP children with pleural effusion requiring thoracocentesis were enrolled in this study. They were subsequently divided into two groups according to the presence or absence of MP in pleural effusion, namely positive group (n = 38) and negative group (n = 127). Information on their clinical manifestations, laboratory findings, radiological characteristics and treatment modalities was retrospectively collected from medical chart reviews. RESULTS: The length of hospitalization (15.00 (10.75-19.25) vs. 11.00 (9.00-14.00) days, p=0.001) and total course of illness (23.00 (18.00-28.00) vs. 20.00 (17.00-24.00) days, p=0.010) were significantly longer in the positive group than in the negative group. The occurrence of pericardial effusion (23.7% vs. 7.9%, p=0.017), atelectasis (73.7% vs. 53.5%, p=0.027) and necrotizing pneumonia (23.7% vs. 7.9%, p=0.017) were more frequent in the positive group compared to the negative group. The levels of neutrophil percentages (82.35% (75.40%-85.78%) vs. 72.70% (64.30%-79.90%), p<0.001), C-reactive protein (CRP) (71.12 (37.75-139.41) vs. 31.15 (13.54-65.00) mg/L, p<0.001), procalcitonin (PCT) (0.65 (0.30-3.05) vs. 0.33 (0.17-1.13) ng/ml, p=0.005), serum lactate dehydrogenase (LDH) (799.00 (589.00-1081.50) vs. 673.00 (503.00-869.00) U/L, p=0.009), D-dimer (6.21 (3.37-16.11) vs. 3.32 (2.12-6.62) mg/L, p=0.001) on admission were significantly higher in the positive group than in the negative group. These pronounced differences significantly contributed to the identification of MPP with MP positive pleural effusion, as evidenced by the ROC curve analysis. Marked elevations in adenosine deaminase (49.25 (36.20-60.18) vs. 36.20 (28.10-46.50) U/L, p<0.001) and LDH levels (2298.50 (1259.75-3287.00) vs. 1199.00 (707.00-1761.00) U/L, p<0.001) were observed in pleural fluid of the positive group when compared to the negative group. Meanwhile, the number of patients on low molecular weight heparin (LMWH) therapy (9 (23.7%) vs. 12 (9.4%), p=0.028) was higher in the positive group. Multivariate logistic regression analysis revealed that D-dimer > 7.33 mg/L was significantly associated with the incidence of MP positive pleural effusion in MPP (OR=3.517). CONCLUSIONS: The presence of MP in pleural fluid in MPP children with pleural effusion indicated a more serious clinical course. D-dimer > 7.33 mg/L was a related factor for MP positive pleural effusion in MPP. The results of the present study would help in the creation of a therapeutic plan and prediction of the clinical course of MPP in children.

Polygenic Score for the Prediction of Postoperative Nausea and Vomiting: A Retrospective Derivation and Validation Cohort Study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a key driver of unplanned admission and patient satisfaction following surgery. Because traditional risk factors do not completely explain variability in risk, we hypothesize that genetics may contribute to the overall risk for this complication. The objective of this research is to perform a genome-wide association study of PONV, derive a polygenic risk score for PONV, assess associations between the risk score and PONV in a validation cohort, and compare any genetic contributions to known clinical risks for PONV. METHODS: Surgeries with integrated genetic and perioperative data performed under general anesthesia at Michigan Medicine and Vanderbilt University Medical Center were studied. PONV was defined as nausea or emesis occurring and documented in the PACU. In the Discovery Phase, genome-wide association studies were performed on each genetic cohort and the results were meta-analyzed. Next, in the Polygenic Phase, we assessed whether a polygenic score, derived from genome-wide association study in a derivation cohort from Vanderbilt University Medical Center, improved prediction within a validation cohort from Michigan Medicine, as quantified by discrimination (C-statistic) and net reclassification index. RESULTS: Of 64,523 total patients, 5,703 developed PONV (8.8%). We identified 46 genetic variants exceeding P<1x10-5 threshold, occurring with minor allele frequency > 1%, and demonstrating concordant effects in both cohorts. Standardized polygenic score was associated with PONV in a basic model, controlling for age and sex, (aOR 1.027 per standard deviation increase in overall genetic risk, 95% CI 1.001-1.053, P=0.044), a model based on known clinical risks (aOR 1.029, 95% CI 1.003-1.055, P=0.030), and a full clinical regression, controlling for 21 demographic, surgical, and anesthetic factors, (aOR 1.029, 95% CI 1.002-1.056, P=0.033). The addition of polygenic score improved overall discrimination in models based on known clinical risk factors (c-statistic: 0.616 compared to 0.613, P=0.028) and improved net reclassification of 4.6% of cases. CONCLUSION: Standardized polygenic risk was associated with PONV in all three of our models, but the genetic influence was smaller than exerted by clinical risk factors. Specifically, a patient with a polygenic risk score > 1 standard deviation above the mean, has 2-3% greater odds of developing PONV when compared to the baseline population, which is at least an order of magnitude smaller than the increase associated with having prior PONV/motion sickness (55%), having a history of migraines (17%), or being female (83%), and is not clinically significant. Furthermore, the use of a polygenic risk score does not meaningfully improve discrimination compared to clinical risk factors and is not clinically useful.

Clusterin-carrying extracellular vesicles derived from human umbilical cord mesenchymal stem cells restore the ovarian function of premature ovarian failure mice through activating the PI3K/AKT pathway.

BACKGROUND: Emerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF. METHODS: Ovarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs. RESULTS: After CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs. CONCLUSIONS: Administration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF.

Unveiling the Role of Pyridinic Nitrogen and Diacetylene in the Hydrogen Evolution Reaction through Model Catalysts Prepared by On-Surface Reactions.

Metal-free carbon materials (MFCMs) have extensive applications in electrocatalysis because of their comparable catalytic activity to that of Pt/C in some cases. Understanding the structure-property relationship is crucial for the reasonable design of more efficient catalysts. To reveal the structure-property relationship of the hydrogen evolution reaction (HER), we prepared nanowire model catalysts on single-crystalline Au(111) electrodes through state-of-the-art on-surface synthesis. Temperature-dependent experiments were conducted to evaluate the HER activity of the nanoribbons functionalized with pyridinic nitrogen and diacetylene. According to our electrochemical results (overpotential, current density j0, and apparent activation energy), we demonstrate that the participation of diacetylene can promote the catalytic reaction for the HER through a synergistic effect. Based on the analysis of the activation entropy for the model catalysts, we attribute the synergistic effect of diacetylene groups to the large area of π···H-O bonding in the electric double layer, thus providing direct insight into the structural-property relationship of polymerized nanoribbons for the HER through the rational design of precursor structures. The nanoribbons prepared by on-surface synthesis can serve as prototype systems for model catalytic research on MFCMs.

The Role of miRNA in Hyperthyroidism Induced by Excessive Iodine in Drinking Water.

In recent years, iodine deficiency-related diseases have been effectively controlled; the prevalence of excessive iodine-induced thyroid diseases has increased, such as hyperthyroidism. However, there are still several controversial outcomes regarding the relationship between excessive iodine intakes and hyperthyroidism. MicroRNAs (miRNAs) extensively participate in the progression of thyroid diseases; nevertheless, the relationship and mechanism between iodine exposure and miRNAs have not been explored in hyperthyroidism patients. In this study, a total of 308 pairs of hyperthyroidism patients and healthy controls were enrolled in. Logistic regression analysis showed that level of water iodine >100 µg/L was an independent risk factor for hyperthyroidism. Compared with the healthy control, the serum thyroglobulin (Tg) content and levels of interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly elevated in hyperthyroidism patients. Further, high-throughput miRNA sequencing was applied to find crucial miRNAs involved in the occurrence of hyperthyroidism related to excessive water iodine. Based on the fold change and Q value, miR-144-3p, miR-204-5p, miR-346, miR-23b-5p, and miR-193b-3p were selected for validation by qRT-PCR. Our results showed that miR-346 and miR-204-5p in the case group were significantly lower than those of the control group, and the similar results found under the level of water iodine >300 µg/L. Nonetheless, no significant difference was found at 10-100 µg/L level of water iodine. Furthermore, the ROC curve indicated that miR-346 and miR-204-5p had the ability to diagnose hyperthyroidism patients. Taken together, excessive water iodine may decrease the expression of miR-346 and miR-204-5p, which mediate the elevation of Tg and cytokines, ultimately making contribution to the development of hyperthyroidism.

Relationship between right-to-left shunt and white matter lesions in patients with migraine: a single-center study.

Background: Migraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs. Methods: In this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs). Results: Among the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p < 0. 001) and a shorter disease duration (6.76 vs. 8.34 years, p = 0.024). The overall proportion of RLS patients was 41.9%, with a greater proportion of RLS patients in the MA group than in the MO group (55.8% vs. 41. 1%, p = 0.037). The percentage of RLS-positive patients with no/small shunt was greater in the MO group than in the MA group (81.5% vs. 65.4%, p = 0.004), whereas the percentage of RLS-positive patients with moderate/large shunt was greater in the MA group (34.6% vs. 18.5%, p = 0.024). The proportion of RLS patients was lower in the WML-positive group (n = 173) than in the WML-negative group (n = 332), but the difference was not significant (40.5% vs. 45.8%, p = 0.253). Conclusion: This study revealed that 41.9% of migraine patients had RLS, and the proportion of RLS patients was 41. 1% in the MO group and 55.8% in the MA group. The rate of RLS positivity in migraine patients may not be related to the incidence of WMLs.