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ABSTRACTBrucellosis is a major threat to public health and animal husbandry. Several in vivo vertebrate models, such as mice, guinea pigs, and nonhuman primates, have been used to study Brucella pathogenesis, bacteria-host interactions, and vaccine efficacy. However, these models have limitations whereas the invertebrate Galleria mellonella model is a cost-effective and ethical alternative. The aim of the present study was to examine the invertebrate G. mellonella as an in vivo infection model for Brucella. Infection assays were employed to validate the fitness of the larval model for Brucella infection and virulence evaluation. The protective efficacy of immune sera was evaluated by pre-incubated with a lethal dose of bacteria before infection. The consistency between the mouse model and the larval model was confirmed by assessing the protective efficacy of two Brucella vaccine strains. The results show that G. mellonella could be infected by Brucella strains, in a dose- and temperature-dependent way. Moreover, this larval model can effectively evaluate the virulence of Brucella strains in a manner consistent with that of mammalian infection models. Importantly, this model can assess the protective efficacy of vaccine immune sera within a day. Further investigation implied that haemolymph played a crucial role in the protective efficacy of immune sera. In conclusion, G. mellonella could serve as a quick, efficient, and reliable model for evaluating the virulence of Brucella strains and efficacy of immune sera in an ethical manner.

Background and objective Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation. Methods A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed. Results The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023). Conclusion Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.

Lung cancer is a life-threatening malignant tumour that is prevalent worldwide. Here, the GCNT3 gene in lung adenocarcinoma was studied via public databases, and cytology and molecular biology experiments were performed to further explore the role of this gene in lung adenocarcinoma. In this study, abnormally high GCNT3 expression levels were observed in tumour tissues compared with normal tissues at both the mRNA and protein levels. In the pancancer analysis, abnormal GCNT3 expression was observed in many tumour types. Moreover, the survival analysis revealed that among patients receiving radiotherapy, those with high GCNT3 expression levels had a worse prognosis. Cell and molecular biology experiments showed that the proliferation, migration and invasion capabilities of the A549 cell line were decreased after knockdown of GCNT3, and epithelial-mesenchymal transformation was significantly inhibited. In subsequent studies, we found that the sensitivity of cells to radiotherapy was enhanced after GCNT3 knockdown. Overall, our findings reveal that GCNT3 is an important factor affecting the radiotherapy sensitivity of lung adenocarcinoma, and GCNT3 inhibition deserves further study as a radiotherapy sensitising strategy.

Adjuvants are crucial components of vaccines that can enhance and modulate antigen-specific immune responses. Herein, we reported for the first time that human metallothionein-3 (MT3), a low molecular weight cysteine-rich metal-binding protein, was a novel promising adjuvant candidate that could help protein antigens to induce rapid, effective, and durable antigen-specific immune responses. In the present study, MT3 was fused to outer membrane protein 19 (Omp19) of Brucella abortus (MT3-Omp19, MO) and C fragment heavy chain (Hc) of tetanus neurotoxin (MT3-Hc, MH), respectively. The results showed that MT3 as a built-in adjuvant increased the Omp19- or Hc-specific antibody responses by 100-1000 folds in seven days after primary immunization. Compared to other commercially available adjuvants, MT3 could stimulate earlier (4 days after primary injection) and stronger (10-100 folds) antibody response with lower antigen dose, and its adjuvanticity relied on fusion to antigen. Although the mechanism was not clear yet, the fusion protein MO was observed to directly activate DCs, promote germinal center formation and improve the speed of Ig class switching. Interestingly, our subsequent study found that other members of the mammalian MT family (human MT1 or murine MT3 for examples) also had potential adjuvant effects, but their effects were lower than human MT3. Overall, this study explored a new function of human MT3 as a novel built-in adjuvant, which may have important clinical application potential in vaccine development against global pandemics.

ObjectiveYTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma.MethodsYTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments.ResultsYTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFβ1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFβ1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma.ConclusionYTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFβ1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.

Abstract Background The robot-assisted laparoscopic management of post-chemotherapy retroperitoneal metastasis and inferior vena cava tumor thrombus secondary to testicular cancer is a challenging task for urologists. Case presentation A pathological examination of a 36-year-old Caucasian man who had undergone a right radical orchiectomy showed mixed testicular germ cell cancer (70% embryonal cancer and 30% seminoma); he had undergone four prior courses of cisplatin, etoposide, and bleomycin chemotherapy and was found to have residual retroperitoneal enlarged lymph nodes close to the right renal hilum and a 9.8 cm inferior vena cava tumor thrombus (pT1, N2, M1, S2). Pre-surgical three-dimensional image reconstruction was performed based on contrast computed tomography data. The inferior vena cava tumor thrombus was found in the vena cava at the level of the celiac trunk and the inferior mesenteric artery. Our patient accepted treatment with robot-assisted laparoscopic retroperitoneal lymph node dissection with concomitant inferior vena cava thrombectomy and cava reconstruction on September 12, 2018. During the procedure, a drop-in robotic ultrasound probe was used to define the thrombus. Vena cavoscopy using a flexible ureteroscope found that the tumor thrombus adhered to the cava wall in all directions. The tumor thrombus was dissected free from the inferior vena cava lumen, and vena cava reconstruction was achieved using the da Vinci™ Si HD surgical system. The operative time was 550 minutes. The intraoperative estimated blood loss was 2300 ml. Intraoperative blood transfusions consisted of 10 units of red blood cells (Clavien-Dindo grade II). No Clavien-Dindo grade III or above perioperative complications occurred. The length of hospital stay was 7 days. Pathology revealed no viable cancer cells in any of the residual lymph node tissues or in the vena cava tumor thrombus. Conclusion This is the first case of robot-assisted laparoscopic retroperitoneal lymph node dissection with concomitant inferior vena cava thrombectomy and reconstruction for metastatic mixed testicular germ cell cancer published to date. This complicated surgical procedure was facilitated by the innovative usage of three-dimensional image reconstruction for defining the vena cava tumor thrombus, a robotic ultrasound probe for intraoperatively defining the vena cava tumor thrombus, and vena cavoscopy using a flexible ureteroscope.

Graphite-based composites are well recognized as ideal functional materials in mechanical seals, bearings of canned pumps, and electrical contact systems because of their outstanding self-lubricating ability, thermostability, and chemical stability. Working in harsh conditions is a huge challenge for the graphite materials, and their tribological properties and wear mechanisms are not well studied. In this study, the tribological performance of metal-impregnated graphite, resin-impregnated graphite, and non-metal-impregnated graphite under high temperature and high load are studied using a ball-on-disc tribometer. The results show that the metal-impregnated graphite (Metal-IG) has a stable friction regime and exhibits better anti-friction and anti-wear properties than that of resin-impregnated graphite (Resin-IG) and non-impregnated graphite (Non-IG) under extreme pressure (200~350 MPa) and high temperature (100–350 °C). The Metal-IG and Resin-IG can reduce the wear depth by 60% and 80%, respectively, when compared with Non-IG substrate. The impregnated materials (metal or resin) can enhance the strength of the graphite matrix and improve the formation of graphite tribofilm on the counterpart surfaces. Friction-induced structural ordering of graphite and slight oxidation of metal in the formed mechanically mixed layer is also beneficial for friction and wear reduction. This study demonstrates the tribological characteristics of impregnated graphite under harsh conditions and provides the experimental basis for the advanced usage of high-reliability and self-lubrication graphite composites.

Background and objective The development of new treatments beyond first-line in metastatic non-small cell lung cancer (NSCLC) contributed to the increase in overall survival. Metronomic chemotherapy involves several mechanisms of anti-tumor with less toxicity. Oral vinorelbine has paved the way for innovative treatment strategies through metronomic regimens. Therefore, this study assessed the efficacy and safety of metronomic oral vinorelbinen in advanced NSCLC after failure to multiple-lines treatments. Methods Our retrospective study enrolled 26 patients who received metronomic oral vinorelbinen. Survival factors were evaluated by univariate regression analysis. Results The median follow-up time was 4 months (range 2-12). The median number of treatment cycles was 2 (range 1-8). No patient achieved complete remission, 2 cases (8%) partial remission, 11 cases (42%) stable disease, 13 cases (50%) progression disease. Overall response rate was 8% and disease control rate was 50%. The median progression-free survival (PFS) was 2 months. In univariate analysis, patients with performance status (PS)=1 had a statistically significantly longer PFS than patients with PS=2. Gender, age, smoking status and histology were not prognostic factors according to PFS. Treatment was well tolerated with rare serious toxicity. No grade 4 adverse events (AEs) or occurrences of intolerable toxicity were observed. There was no treatment-related death and none of the study patients required hospitalization for treatment-related adverse events. Conclusion Metronomic oral vinorelbinen is effective in advanced NSCLC after the failure of multiple lines treatments with an acceptable AE profile, especially in patients with high PS.

Background and objective Status of epidermal growth factor receptor (EGFR) gene is a predictor of response to EGFR tyrosine kinase inhibitor (TKI). However, little is know about the relationship between EGFR status and response to chemotherapy. We evaluated the prediction value of EGFR mutation status on response to first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The data of 181 patients with stage IIIb/IV NSCLC who diagnosed by histopathology from January 10, 2006 to December 20, 2013 in Beijing Chest Hospital, Capital Medical University were collected. The relationships between EGFR gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. Results All of the 181 patients’ EGFR statuses were determined. 75 (41.4%) patients harbored EGFR-activating mutations and 106 (58.6%) patients were EGFR wild-type. All patients received first-line chemotherapy. The objective response rate (ORR) was 26.0% and disease control rate (DCR) was 70.2%. Patients with EGFR-activating mutations had a higher DCR than patients with EGFR wild-type (84.0% vs 60.4%, P=0.001) did. Subgroup analysis showed that the ORR and DCR in patients with EGFR exon 19 deletions were remarkably higher than those with EGFR wild-type (P = 0.049, 0.002, respectively). The DCR in patients with EGFR exon 21 L858R mutation was significantly higher than that in patients with EGFR wild-type (P=0.010). 168 patients were available for response evaluation in all of 181 patients and median PFS was 4.3 mo. The PFS of patients with adenocarcinoma was significantly higher than that patients with squamous cell carcinoma (4.7 mo vs 3.0 mo, P=0.036). The PFS in patients harbored EGFR-activating mutations was significantly higher than that in the patients with EGFR wild-type (6.3 mo vs 3.0 mo, P=0.002). The PFS of patients with a performance status (PS) of 0-1 was significantly higher than that in patients with a PS of 2 (4.4 months vs. 0.7 months, P= 0.016). Cox multivariate analysis indicates the EGFR-activating mutation is an independent factor affecting PFS (HR=0.654, 95%CI: 0.470-0.909, P=0.012). Conclusion EGFR-activating mutation is a predictor for PFS of first-line chemotherapy in advanced NSCLC patients.

Background and objective Results of studies on genetic polymorphisms of ERCC1 gene in DNA repair pathway which may affect response to platinum-based chemotherapy and survival in patients with non-small cell lung cancer are conflicting. The aim of this study is to prospectively assess the association between single nucleotide polymorphisms of C8092A and codon118 in ERCC1 and drug response in 90 patients with advanced non-small cell lung cancer treated with cisplatin-based chemotherapy. Methods All patients were treated with cisplatin-based chemotherapy. Genotypes of ERCC1 C8092A and codon118 were examined by sequencing, and the association between genotypes and response was evaluated. Results Genotype frequencies of ERCC1 C8092A were CC 40.0% (36/90), CA 48.9% (44/90) and AA 11.1% (10/90), frequencies of codon118 were CC 58.9% (53/90), CT 34.4% (31/90) and TT 6.7% (6/90). There was no significant difference in response rate of patients carrying with CC, compared with CA plus AA in C8092A (33.3% vs 29.6%, P=0.71). Response rate of patients carrying with CC in ERCC1 118 was 32.1%, 24.3% with CT plus CC (P=0.43). There was no difference in progression free survival between patients carrying with CC and CT plus TT in C8092A (5.2 months vs 5.4 months, P=0.62). There was no difference in progression free survival between patients carrying with CC and CA plus AA (5.5 months vs 5.3 months, P=0.59). Conclusion The results suggest that there is no association between polymorphisms in ERCC1 C8092A and codon118 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy.

Background and objective GSTM1 takes part in the metabolism of environmental pollutants such as benzopyrene other polycyclic aromatic hydrocarbons and anticancer drugs and so on. The study aims to investigate the relationship between the gene polymorphism of GSTM1 and chemotherapy as well as to study the effect to survival of Chinese patients with lung cancer. Methods The genotypes of GSTM1 were examined with polymerase chain reaction in 137 primary lung cancer patients accepted chemotherapy. Results GSTM1 -null genotype frequency was 58.4%(80?137). The frequency of non-null GSTM1 genotype was 41.6%(57?137). The frequency of GSTM1-null genotype was 69.05%(58?84) in the response group of chemotherapy and 41.51%(22?53) in the non-response group of chemotherapy. They were significantly different (P=0.001). In the patients with platinum chemotherapy, the frequency of GSTM1-null genotype was 65.43%(53?81) in the response group of chemotherapy and 42%(21?50) in the non-response group. There werestastically differences in them (P=0.0025). For the advanced cases, GSTM1 -null genotype frequency was 70.13% (54 ? 77) in the response group of chemotherapy, 41.51% (22?53) in the non-response group of chemotherapy respectively and they were significantly different(P=0.001). When the chemotherapy was effective, the survival time of patients in squamous carcinoma and small cell carcinoma with non-null GSTM1 genotype (the median survival times were 42 months and 14 months respectively) were longer than those with null GSTM1 genotype (the median survival times were 6 months and 7 months respectively)(P0.05. When chemotherapy was not effective, the median survival time were not significantly different (P>0.05). Conclusions The effect of chemotherapy of GSTM1-null genotype patients was better than that of GSTM1-postive genotype patients. The chemotherapy effect of the cases with null GSTM1 type was better than those with non-null GSTM1 type when the patients accepted platinum chemotherapy. When the chemotherapy was effective, the survival time may be related to the histological types and GSTM1 genotypes.

Background and objective Docetaxel is an active agent in the second-line treatment for non-small cell lung cancer (NSCLC), many clinical trials have demonstrated that it has similar efficacy to common first-line regimens for NSCLC. A randomized study was conducted to compare docetaxel plus cisplatin (DC) versus paclitaxel plus cisplatin (PC) for patients with advanced non-small cell lung cancer as the first-line regimen. Methods Ninety patients with previously untreated advanced non-small cell lung cancer were randomly assigned to receive either DC or PC. Patients received docetaxel 75mg/m2 on day 1 and cisplatin 75mg/m2 divided into two doses on days 2 to 3 in DC group and paclitaxel 150mg/m2 on day 1 and cisplatin 75mg/m2 divided into two doses on days 2 to 3 in PC group. The cycle of two regimens was repeated every 3 weeks. Response and toxicity were evaluated inpatients who completed two cycles of chemotherapy at least. Results Overall survival rate was 31.1% in DC group and 33.3 % in PC group. The median survival time was 10.2 months in DC group and 10.4 months in PC group.Median time to tumor progression was 4.4 months in DC group and 4.9 months in PC group. 1- and 2-year survival rate were 35.6% and 8.9% in DC group and 37.8% and 11.1% in PC group respectively. There were no significant differences in response rate, median survival time, median time to tumor progression and survival rate between two groups (P

Abstract Background Exploring the physiological and molecular mechanisms underlying goat sexual maturation can enhance breeding practices and optimize reproductive efficiency and is therefore substantially important for practical breeding purposes. As an essential neuroendocrine organ in animals, the hypothalamus is involved in sexual development and other reproductive processes in female animals. Although microRNAs (miRNAs) have been identified as significant regulators of goat reproduction, there is a lack of research on the molecular regulatory mechanisms of hypothalamic miRNAs that are involved in the sexual development of goats. Therefore, we examined the dynamic changes in serum hormone profiles and hypothalamic miRNA expression profiles at four developmental stages (1 day (neonatal, D1, n = 5), 2 months (prepubertal, M2, n = 5), 4 months (sexual maturity, M4, n = 5), and 6 months (breeding period, M6, n = 5)) during sexual development in Jining grey goats. Results Transcriptome analysis revealed 95 differentially expressed miRNAs (DEMs) in the hypothalamus of goats across the four developmental stages. The target genes of these miRNAs were significantly enriched in the GnRH signalling pathway, the PI3K-Akt signalling pathway, and the Ras signalling pathway (P

Abstract The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat’s sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.

Background We aimed to investigate the associations of long‐term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. Methods and Results Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long‐term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02–1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29–2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54–4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02–1.58]), rural areas (HR, 1.22 [95% CI, 0.94–1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02–1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17–37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. Conclusions Long‐term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde‐induced angina pectoris symptoms.

Abstract Goats can provide meat, milk and skins for humans and are livestock with high economic benefits. However, despite their economic significance, the comprehensive analysis of goats’ serum metabolic profile and its intricate alterations throughout their developmental journey remains conspicuously absent. To investigate the stage-specificity and dynamic change characteristics of metabolites during the growth and development of goats, this study compared the alterations in serum hormone levels and serum biochemical markers across different developmental stages of female goats (1, 60, 120 and 180 days old; n = 5). Additionally, a serum untargeted LC–MS metabolomics analysis was conducted. A total of 504 DAMs were identified with age. The results indicated that PE, PC, Lyso-PE, Lyso-PC and FAFHA may play important roles in lipid metabolism in goats after birth. Weighted gene co-expression network analysis (WGCNA) identified two metabolite modules (Turquoise and Yellow) and key metabolites within these modules that were significantly associated with phenotypic features. l-carnitine may be a metabolite related to muscle development in goats. The findings of this study demonstrate notable variations in serum metabolites across distinct developmental phases in goats. Lipids and organic acids play important roles in different developmental stages of goats.

The hypothalamus is an essential neuroendocrine area in animals that regulates sexual development. Long non-coding RNAs (lncRNAs) are hypothesized to regulate physiological processes related to animal reproduction. However, the regulatory mechanism by which lncRNAs participate in sexual maturity in goats is poorly known, particularly from birth to sexual maturation. In this study, RNAseq analysis was conducted on the hypothalamus of four developmental stages (1day (D1, n = 5), 2 months (M2, n = 5), 4 months (M4, n = 5), and 6 months (M6, n = 5)) of Jining grey goats. The results showed that a total of 237 differentially expressed lncRNAs (DELs) were identified in the hypothalamus. Among these, 221 DELs exhibited cis-regulatory effects on 693 target genes, while 24 DELs demonstrated trans-regulatory effects on 63 target genes. The target genes of these DELs are mainly involved in biological processes related to energy metabolism, signal transduction and hormone secretion, such as sphingolipid signaling pathway, adipocytokine signaling pathway, neurotrophic signaling pathway, glutamatergic synapse, P53 signaling pathway and GnRH signaling pathway. In addition, XR_001918477.1, TCONS_00077463, XR_001918760.1, and TCONS_00029048 and their potential target genes may play a crucial role in the process of goat sexual maturation. This study advances our understanding of lncRNA in hypothalamic tissue during sexual maturation in goats and will give a theoretical foundation for improving goat reproductive features.

Abstract Background The ovary is an important reproductive organ in mammals, and its development directly affects the sexual maturity and reproductive capacity of individuals. MicroRNAs (miRNAs) are recognized as regulators of reproductive physiological processes in various animals and have been shown to regulate ovarian development through typical targeting and translational repression. However, little is known about the regulatory role of miRNAs in ovarian tissue development during sexual maturity in goats. To comprehensively profile the different physiological stages of sexual maturation in goats, we performed small-RNA sequencing of ovarian tissue samples collected at four specific time points (1 day after birth (D1), 2 months old (M2), 4 months old (M4), and 6 months old (M6)). In addition, we used ELISAs to measure serum levels of reproductive hormones to study their temporal changes. Results The results showed that serum levels of gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, oestradiol, progesterone, oxytocin, and prolactin were lower in goats at the D1 stage than at the other three developmental stages (P 1, FDR

Abstract Quantification of the cardiac function is vital for diagnosing and curing the cardiovascular diseases. Left ventricular function measurement is the most commonly used measure to evaluate the function of cardiac in clinical practice, how to improve the accuracy of left ventricular quantitative assessment results has always been the subject of research by medical researchers. Although considerable efforts have been put forward to measure the left ventricle (LV) automatically using deep learning methods, the accurate quantification is yet a challenge work as a result of the changeable anatomy structure of heart in the systolic diastolic cycle. Besides, most methods used direct regression method which lacks of visual based analysis. In this work, a deep learning segmentation and regression task-unified network with transformer and spatial–temporal convolution is proposed to segment and quantify the LV simultaneously. The segmentation module leverages a U-Net like 3D Transformer model to predict the contour of three anatomy structures, while the regression module learns spatial–temporal representations from the original images and the reconstruct feature map from segmentation path to estimate the finally desired quantification metrics. Furthermore, we employ a joint task loss function to train the two module networks. Our framework is evaluated on the MICCAI 2017 Left Ventricle Full Quantification Challenge dataset. The results of experiments demonstrate the effectiveness of our framework, which achieves competitive cardiac quantification metric results and at the same time produces visualized segmentation results that are conducive to later analysis.

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was

Background: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and its specific components with hypertension and blood pressure is limited. Methods: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007–2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. Results: Each interquartile range (IQR = 16.80 μg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR μg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42−, NO3−, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. Conclusions: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Abstract Background There is no general agreement on the preferential use of a fixed ratio (FR) of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Abstract Precise assembly of biomolecules into functional aggregate structures represents a key characteristic of nature living cells, and is critical for the cellular processes. The construction of artificial aggregates in living cells by responding to intracellular specific stimuli has been applied in elucidating molecular mechanisms of naturally cellular processes and interfering with cellular processes, which is potential and significant in biomedicine. DNA (deoxyribonucleic acid) features sequence programmability, precise assembly and versatility, and therefore is regarded as the potential candidate for constructing versatile functional aggregates in living cells. In this review, we summarize our recent efforts of employing DNA to in situ construct versatile aggregates in living cells via responding intracellular triggers, and the subsequent bio‐interference of the DNA aggregates. Finally, we discuss the remaining challenges and opportunities in the field, and envision that rational design and construction of versatile DNA aggregates in living system would be a promising solution for precision and personalized therapeutics.

Objective We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. Methods Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. Results After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 − 0.71); specificity 0.72 (0.71 − 0.73), PPV 0.25 (0.24 − 0.26) and NPV 0.94 (0.94 − 0.95). Conclusion We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Abstract Background Patients with severe acute exacerbations of chronic obstructive pulmonary disease often have a poor prognosis. Biomarkers can help clinicians personalize the assessment of different patients and mitigate mortality. The present study sought to determine if the lymphocyte count could act as a risk factor for mortality in individuals with severe AECOPD. Methods A retrospective study was carried out with 458 cases who had severe AECOPD. For analysis, patients were divided into two groups on the basis of lymphocyte count:

Objective: The search for rapid and effective early diagnostic markers of hypotharyngeal carcinoma becomes particularly critical and important. Therefore, we explored the value of circulating expression of non-coding RNAs for the diagnosis of early hypotharyngeal cancer. Methods: After screening HPSCC-related research data in the NCBI-GEO database, the practical report extraction language (Perl) was used to give genes different biotype attributes. The R language limma package was utilized to analyze the differential expression of lncRNAs and mRNAs, respectively.The quantitative RT-PCR (Reverse transcription-polymerase chain reaction) analysis were performed to determine the plasma expression levels of non-coding RNAs Results: Compared with the control groups, the differential expression of 137 lncRNAs and 297 mRNAs in the plasma of HPSCC patients was statistically significant. There were 32 differentially expressed lncRNAs, 19 differentially expressed mRNAs. The score of LncRNA AC018761 + miR-488 was AUC = 0.846, the best cut-off value was ≥ 40 points, the sensitivity was 74.58%, and the specificity was 79.88%. Conclusion: Our results indicated that the over-expression of lncRNA-AC018761 and miR-488 were significantly up-regulated in serum of patients with HPSCC. Therefore, lncRNA-AC018761 and miR-488 maybe the non-invasive independent predictor for early HPSCC with high sensitivity and specificity.

BackgroundData on which frailty scales are most suitable for estimating risk in Chinese community populations remain limited. Herein we examined and compared four commonly used frailty scales in predicting adverse outcomes in a large population-based cohort of Chinese older adults.MethodsA total of 5402 subjects (mean age 66.3 ± 9.6 years, 46.6% male) from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Frailty was measured using a 35-item frailty index (FI), the frailty phenotype (FP), FRAIL, and Tilburg Frailty Indicator (TFI). Multivariate logistic regression models were performed to evaluate the independent association between frailty and outcomes including 4-year disability, hospitalization, and 4- and 7-year all-cause mortality. The accuracy for predicting these outcomes was determined by evaluating the area under the curve (AUC). The prevalence of frailty, sensitivity, and specificity were calculated using our proposed cut-off points and other different values.ResultsPrevalence of frailty ranged from 4.2% (FRAIL) to 16.9% (FI). FI, FRAIL and TFI were comparably associated with 4-year hospitalization, and 4- and 7-year mortality (adjusted odds ratios [aORs] 1.44–1.69, 1.91–2.22 and 1.85–2.88, respectively). FRAIL conferred the greatest risk of 4-year disability, followed by FI and TFI (aOR 5.55, 3.50, and 1.91, respectively). FP only independently predicted 4- and 7-year mortality (aOR 1.57 and 2.21, respectively). AUC comparisons showed that FI, followed by TFI and FRAIL, exhibited acceptable predictive accuracy for 4-year disability, 4- and 7-year mortality (AUCs 0.76–0.78, 0.71–0.71, 0.65–0.72, respectively), whereas all scales poorly predicted 4-year hospitalization (AUCs 0.53–0.57). For each scale, while specificity estimates (85.3–97.3%) were high and similar across all outcomes, their sensitivity estimates (6.3–56.8%) were not sufficient yet. Prevalence of frailty, sensitivity, and specificity varied considerably when different cut-off points were used.ConclusionFrailty defined using any of the four scales was associated with an increased risk of adverse outcomes. Although FI, FRAIL and TFI exhibited fair-to-moderate predictive accuracy and high specificity estimates, their sensitivity estimates were not sufficient yet. Overall, FI performed best in estimating risk, while TFI and FRAIL were additionally useful, the latter perhaps being more applicable to Chinese community-dwelling older adults.

Background: Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the effects of ambient PM on asthma in high altitude settings. Methods: The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM2.5 and PM10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates. Results: We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2–4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5–5.1) than in men (3.1%, 2.4–3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 μg/m3) in PM2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46–1.83, P

Abstract Background Social capital has a potential effect in protecting oral health among population. However, no study has explored the association between social capital and oral health in the Chinese context. Due to the unique culture, political, social context in China, it is important to understand their association in the Chinese context. The study aims to investigate the association between cognitive and structural dimensions of social capital with edentulism among adults aged 50 years and over in China. Method The study used data from the WHO SAGE (Study on Global AGEing and Adult Health) wave 1 China component. Structural social capital was operationalized as social participation. Cognitive social capital was operationalized as perceived community trust and perceived community safety. Community-level social capital was measured by aggregating individual-level social capital into community level. Oral health was measured using a final marker of oral health status, self-reported edentulism. A 2-level multilevel logistic regression was used to evaluate the association between different dimensions of social capital and oral health. Results In total, 12,856 individuals were included in the study, the overall prevalence of edentulism was 9.1% (95% CI 8.3–10.0). Multilevel logistic analysis revealed that individual-level social capital and community-level social capital are independently associated with edentulism. Individuals with low structural social capital and living in areas with low structural social capital have, respectively, 1.54 (95% CI 1.18–2.01) and 2.14 (95% CI 1.47–3.12) times higher odds for edentulism, after adjustment for potential confounders (age, sex, marital status, residence locality, wealth, education level, chronic conditions) and a potential mediator(smoking). Conclusions Living in a community with lower structural social capital and individual with low structural social capital is associated with higher risk for edentulism among adults aged 50 years and over in China.

Abstract Segmentation of intracranial aneurysm images acquired using magnetic resonance angiography (MRA) is essential for medical auxiliary treatments, which can effectively prevent subarachnoid hemorrhages. This paper proposes an image segmentation model based on a dense convolutional attention U-Net, which fuses deep and rich semantic information with shallow-detail information for adaptive and accurate segmentation of MRA-acquired aneurysm images with large size differences. The U-Net model serves as a backbone, combining dense block and convolution block attention module (CBAM). The dense block is composed of a batch normalization layer, an randomly rectified linear unit activation function, and a convolutional layer, for mitigation of vanishing gradients, for multiplexing of aneurysm features, and for improving the network training efficiency. The CBAM is composed of a channel attention module and a spatial attention module, improving the segmentation performance of feature discrimination and enhancing the acquisition of key feature information. Owing to the large variation of aneurysm sizes, multi-scale fusion is performed during up-sampling, for adaptive segmentation of MRA-acquired aneurysm images. The model was tested on the MICCAI 2020 ADAM dataset, and its generalizability was validated on the clinical aneurysm dataset (aneurysm sizes: 7 mm) supplied by the Affiliated Hospital of Qingdao University. A good clinical application segmentation performance was demonstrated.

Abstract The accurate and robust automatic segmentation of cardiac structures in magnetic resonance imaging (MRI) is significant in calculating cardiac clinical functional indices, and diagnosing heart diseases. Most U‐Net based methods use pooling, transposed convolution, and skip connection operations to integrate the multiscale features for improved segmentation in cardiac MRI. However, this architecture lacks adequate semantic connection between the channel and spatial information, and robustness in segmenting objects with significant shape variations. In this paper, a new multiscale feature attentive U‐Net for cardiac MRI structural segmentation method is proposed. An attention mechanism is adopted after concatenating the multi‐level features to aggregate different scale features and determine on which features to focus. Cascade and parallel dilated convolution is also employed in the decoder blocks and skip connection is employed to enhance the ability of sensing receptive fields for multiscale context information. Furthermore, deep supervision approach with a loss function that combines the dice and cross‐entropy losses to reduce overfitting and ensure better prediction is introduced. The proposed method was evaluated on three public cardiac datasets. The experimental results indicate that the method achieved competitive segmentation performance with the three datasets, which verifies the robustness and generalisability of the proposed network. In comparison with conventional U‐Net methods, the model leverages attention mechanism and dilated convolution block, which increases the semantic connection between the channel and the spatial information, and improves the robustness of the right ventricle segmentation performance. From the view of the Dice scores and segmentation results, the multiscale feature attentive U‐Net method is one of effective methods in segmenting cardiac MRI structures.

Abstract Pulmonary nodules are the main manifestation of early lung cancer. Therefore, accurate detection of nodules in CT images is vital for lung cancer diagnosis. A 3D automatic detection system of pulmonary nodules based on multi-scale attention networks is proposed in this paper to use multi-scale features of nodules and avoid network over-fitting problems. The system consists of two parts, nodule candidate detection (determining the locations of candidate nodules), false positive reduction (minimizing the number of false positive nodules). Specifically, with Res2Net structure, using pre-activation operation and convolutional quadruplet attention module, the 3D multi-scale attention block is designed. It makes full use of multi-scale information of pulmonary nodules by extracting multi-scale features at a granular level and alleviates over-fitting by pre-activation. The U-Net-like encoder-decoder structure is combined with multi-scale attention blocks as the backbone network of Faster R-CNN for detection of candidate nodules. Then a 3D deep convolutional neural network based on multi-scale attention blocks is designed for false positive reduction. The extensive experiments on LUNA16 and TianChi competition datasets demonstrate that the proposed approach can effectively improve the detection sensitivity and control the number of false positive nodules, which has clinical application value.

Due to the existence of many disulfide bonds in japonica rice bran protein (JRBP) molecules, their solubility is poor, which seriously affects other functional properties. To improve the functional characteristics of JRBP molecules, they were processed by ultrasound technology, and JRBP-catechin (CC) covalent complex was prepared. The structural and functional properties of indica and japonica rice bran proteins and their complexes were compared; furthermore, the changes in the structural and functional properties of JRBP-CC under different ultrasound conditions were investigated. The results showed that compared with indica rice bran protein (IRBP), the secondary structure of JRBP-CC was very different, the water holding capacity (WHC) was higher, and the emulsification performance was better. Different ultrasound conditions had different effects on the functional properties of JRBP-CC. When the ultrasound power was 200 W, the λmax redshift of the JRBP-CC complex was the most significant, the particle size was the smallest, the absolute value of the zeta potential was the largest, and the hydrophobicity and microstructure of the JRBP-CC complex were the best. Concurrently, the maximum WHC and oil holding capacity (OHC) of JRBP-CC under these conditions were 7.54 g/g and 6.87 g/g, respectively. Moreover, the emulsifying activity index (EAI) and emulsifying stability index (ESI) were 210 m2/g and 47.8 min, respectively, and the scavenging activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ABTS+ were 71.96 % and 80.07 %, respectively.