Attitudes toward uncertain results from prenatal exome sequencing: a national survey among healthcare professionals working in the prenatal setting.

Objective: The objective of this study was to investigate the attitudes of healthcare professionals (HPs) working in the prenatal setting toward uncertain results (UR) from prenatal exome sequencing (pES) in China. Methods: We conducted a national survey among HPs working in the prenatal setting. UR in our study include variants of uncertain significance (VUS), variants with variable penetrance/expressivity (VVPE), and secondary findings unrelated to the indication for testing (SFs). A total of 285 questionnaires that met the inclusion criteria were collected. Data were analyzed using IBM SPSS Statistics 26. Results: When performing the pre-test counseling, only 7.4% of HPs mentioned the possibility of VUS, 6.3% discussed the possibility of VVPE, and 7.4% introduced the SFs with parents with the option to not report these variants. In post-test counseling, 73.0-82.8% HPs discussed with the parents but did not make any recommendations for managing the pregnancy after reporting UR (73.0% for VUS, 82.8% for VVPE, 74.7% for SFs, respectively). Conclusion: Most parents did not have the option of opting out of reporting UR from pES in pre-test counseling. UR did not influence the pregnancy recommendation made by most HPs. Establishing national guidelines for reporting UR from pES and developing strategies to improve counseling skills may help HPs manage UR.

Clinical Efficacy of Sodium Cantharidate Vitamin B6 Combined with Concurrent Chemoradiotherapy in the Treatment of Local Advanced Cervical Cancer and its Influence on Tumor Markers.

Objective: To explore the clinical efficacy of sodium cantharidate vitamin B6 combined with concurrent chemoradiotherapy in the treatment of local advanced cervical cancer and its influence on tumor markers. Methods: A total of 120 patients with locally advanced cervical cancer were enrolled at our hospital from January 2021 to December 2022, and these cases were randomly divided into two groups using a random number table method. The control group was treated with concurrent chemoradiotherapy, while the study group was treated with sodium cantharidate vitamin B6 on the basis of the control group. The clinical efficacy, changes in self-immune function (CD3+, CD4+, CD4+/CD8+ cells ratio), tumor marker levels [Squamous Cell Carcinoma Antigen (SCCA), Carbohydrate Antigen 125 (CA125), Carcinoembryonic Antigen (CEA)], quality of life (Nottingham Health Profile questionnaire), and incidence of adverse events were compared between the two groups. Results: After treatment, there was no significant difference in the overall efficacy and disease control rates between the two groups (P > .05). Before treatment, there was no difference in auto-immune function between the two groups (P > .05). However, after treatment, the study group showed a significant improvement in auto-immune function, and when compared to the control group, the levels of CD3+, CD4+ cells, and the ratio of CD4+/CD8+ cells were higher in the study group (P < .05). Before treatment, there was no difference in tumor markers between the two groups (P > .05). While after treatment, tumor markers in both groups decreased significantly, and in comparison to the control group, the levels of SCCA, CA125, and CEA in the study group were lower (P < .05). Before treatment, there was no significant difference in the quality of life between the two groups (P > .05). However, after treatment, the quality of life in both groups improved, and the study group had a higher quality of life score than the control group (P < .05). There was no significant difference in thrombocytopenia between the two groups (P > .05). The total incidence of leukopenia, neutropenia, and radio-chemotherapy-related gastroenteritis in the study group was lower than that in the control group (P < .05). Conclusions: Sodium cantharidate vitamin B6 combined with concurrent chemoradiotherapy in the treatment of local advanced cervical cancer can not only effectively enhance the autoimmune function, downregulate the level of tumor markers, and improve the quality of patient life, but also cause relatively few adverse reactions.

The clinical significance of intraoperative adverse events in laparoscopic radical hysterectomies for early-stage cervical cancer.

OBJECTIVE: Surgical quality plays a vital role in the treatment of malignant tumors. We investigated the classification of intraoperative adverse events (iAE) (ClassIntra) in relation to the surgical quality control of laparoscopic radical hysterectomies. METHODS: A prospective cohort of 195 patients who had undergone laparoscopic radical hysterectomies for early stage cervical cancer between July 2019 and July 2021 was enrolled. Participants were classified into either an iAE or non-iAE groups in accordance with their intraoperative status. Surgical outcomes, patient satisfaction, and quality of life were compared between the two groups. RESULTS: Overall, 48 (24.6%) patients experienced 71 iAE. The iAE group was associated with significantly longer operative times (mean: 270 vs. 245 min, P < 0.001), greater blood loss (mean: 215 vs. 120 mL, P < 0.001), and longer postoperative hospital stays (median: 16 vs. 11 days). Larger tumors and poor technical performance significantly increased the risk of iAE (P < 0.05). Multivariate analysis revealed that iAE were the only independent risk factors for postoperative complications (hazard ratio, 15.100; 95% confidence interval: 4.735-48.158, P < 0.001). Moreover, patients who experienced iAE had significantly lower satisfaction scores and poorer quality of life (P < 0.05). CONCLUSIONS: ClassIntra may serve as an effective adjunctive tool for surgical quality control in laparoscopic radical hysterectomies.

Higher waist circumference is associated with increased likelihood of female infertility: NHANES 2017-2020 results.

Background: Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility. Methods: This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis. Results: We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. (tertile 1, 7.55%; tertile 2, 10.56%; tertile 3, 15.28%; trend < 0.001). Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women (OR1.02; 95% CI 1.01-1.03), and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility (p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm. Conclusion: Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention.

Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.

OBJECTIVE: The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats. METHODS: Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models (n = 6 per group), and then administered with TGs (10 mg/kg·d-1), prednisone (6.3 mg/kg·d-1), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules. RESULTS: After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3. CONCLUSION: TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS.

Ultrasonic pretreatment of spodumene with different size fractions and its influence on flotation.

The potential of ultrasonic pretreatment enhancing selective surface dissolution to improve the floatability of spodumene with different size fractions was verified and investigated. For coarse particles of -0.15 + 0.0385 mm, compared with traditional pretreatment methods, ultrasonic pretreatment could optimize the physicochemical properties of the surface, markedly increased the amount of NaOL adsorbed on the mineral surface, and improved the floatability of the spodumene. For fine particles of -0.0385 mm, both pretreatment methods (Ultrasonic and Traditional) could greatly increase the flotation recovery, but ultrasonic pretreatment had no obvious advantage compared with traditional method. ICP combined with XPS analysis were conducted to investigate the dissolution mechanism of spodumene surface in different pretreatment system. Si species on the surface of coarse particles were easily dissolved into the solution under the effect of ultrasound, which increases the relative content of Al and Li species on the surface. This was conducive to the adsorption of the collectors on the surface. However, the selective dissolution of the fine particle surface was weakened by excessive energy intake in the ultrasonic system, which neutralized the advantage brought by the large amount of dissolution, making the results obtained by the two preprocessing methods the same.

[Ecological network construction and optimization in Foshan City, China]. / 佛山市生态网络构建及优化.

Under the background of rapid urbanization, the problem of fragmented habitat patches in economically developed areas is particularly prominent, where biodiversity is seriously threa-tened. Therefore, the construction of ecological network is an important measure to connect habitat patches and protect biological habitats. We extracted ecological source areas of Foshan City by using the connectivity index and morphological spatial pattern analysis (MSPA). Potential ecological corridors were identified based on InVEST model and minimal cumulative resistance (MCR). Combining the radiation channels extracted from hydrological analysis to build an ecological network in Foshan City. The ecological network was optimized by adding ecological source areas, stepping stones, and identifying fracture points. Finally, the network before and after optimization was evalua-ted from the aspects of both structure and function based on network analysis method and circuit theory. The results showed that ecological network in Foshan City was composed of 10 ecological source areas, 8 important corridors, 37 general corridors, and 11 radiation channels. After optimization, 7 new ecological source areas, 17 planning corridors, 13 stepping stones, and 80 fracture points were added. After optimization, the ecological network closure, the line rate index and the connection degree index were 0.59, 1.94, and 0.73, respectively. The maximum current density increased from 1.39 to 9.66 after optimization, indicating that the optimized ecological network structure was more perfect and highly connective.

Downregulation of lncRNA IGF2-AS-encoded peptide induces trophoblast - cycle arrest.

RESEARCH QUESTION: lncRNA IGF2-AS may be related to early pregnancy loss. Does lncRNA IGF2-AS affect trophoblast cell growth? The aim of the present study was to verify that lncRNA IGF2-AS encodes a polypeptide, IGF2-AS-168aa, and to study its role in the pathogenesis of trophoblasts. DESIGN: A small interfering RNA targeted to the IGF2-AS gene (si-IGF2-AS) was designed and transfected into JEG-3 and JAR cells for in-vitro gene silencing. Quantitative polymerase chain reaction and western blotting were used to determine lncRNA IGF2-AS levels in experimental cells. After IGF2-AS suppression, MTT assay was used to assess cell proliferation and apoptosis was determined by flow cytometry. Target gRNA IGF2-AS-gRNA was designed for knockout conducted the corresponding mRNA. HEK293T cells were transfected with the identified positive clone vectors. Finally, IGF2-AS-168aa was analysed by western blotting after the protein-coding region of the IGF2-AS gene was knocked out by CRISPR/Cas9 gene-editing technology. RESULTS: lncRNA IGF2-AS and IGF2-AS-168aa were significantly downregulated in JEG-3 and JAR cells transfected with si-IGF2-AS (lncRNA IGF2-AS: JAR: NC versus small interfering RNA (siRNA)-1: P = 0.019 NC versus siRNA-2: P = 0.013; JEG-3: NC versus siRNA-1: P = 0.001 NC versus siRNA-2: P = 0.004) (IGF2-AS-168aa: JAR: NC versus siRNA-1: P = 0.030 NC versus siRNA-2: P = 0.018; JEG-3: NC versus siRNA-1: P = 0.004 NC versus siRNA-2: P = 0.001). IGF2-AS gene was incapable of encoding IGF2-AS-168aa after the coding region was successfully knocked out in HEK293T cells. Flow cytometry and the MTT assay revealed that IGF2-AS gene silencing led to cell cycle block in the G1 phase, markedly decreasing cell proliferation and increasing apoptosis. CONCLUSION: The IGF2-AS gene encoded a peptide with a potential function in trophoblast cell cycle arrest.

Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage.

Magnetic field (MF) is being used in antitumor treatment; however, the underlying biological mechanisms remain unclear. In this study, the potency and mechanism of a previously published tumor suppressing MF exposure protocol were further investigated. This protocol, characterized as a 50 Hz electromagnetic field modulated by static MF with time-average intensity of 5.1 mT, when applied for 2 h daily for over 3 consecutive days, selectively inhibited the growth of a broad spectrum of tumor cell lines including lung cancer, gastric cancer, pancreatic cancer and nephroblastoma. The level of intracellular reactive oxygen species (ROS) increased shortly after field exposure and persisted. Subsequently, pronounced DNA damage and activation of DNA repair pathways were identified both in vitro and in vivo. Furthermore, use of free radical scavenger alleviated DNA damage and partially reduced cell death. Finally, this field was found to inhibit cell proliferation, and simultaneously induced two types of programmed cell death, apoptosis and ferroptosis. In conclusion, this tumor suppressing MF could determine cell fate through ROS-induced DNA damage, inducing oxidative stress and activation of the DNA damage repair pathways, eventually lead to apoptosis and ferroptosis, as well as inhibition of tumor growth.

Proteomics and molecular network analyses reveal that the interaction between the TAT-DCF1 peptide and TAF6 induces an antitumor effect in glioma cells.

Glioblastoma is the most lethal brain cancer in adults. Despite advances in surgical techniques, radiotherapy, and chemotherapy, their therapeutic effect is far from significant, since the detailed underlying pathological mechanism of this cancer is unclear. The establishment of molecular interaction networks has laid the foundation for the exploration of these mechanisms with a view to improving therapy for glioblastoma. In the present study, to further explore the cellular role of DCF1 (dendritic cell-derived factor 1), the proteins bound to TAT-DCF1 (transactivator of transcription-dendritic cell-derived factor 1) were identified, and biosystem analysis was employed. Functional enrichment analyses indicate that TAT-DCF1 induced important biological changes in U251 cells. Furthermore, the established molecular interaction networks indicated that TAT-DCF1 directly interacted with TAF6 in glioma cells and with UBC in HEK293T (human embryonic kidney 293T) cells. In addition, further biological experiments demonstrate that TAT-DCF1 induced the activation of the RPS27A/TOP2A/HMGB2/BCL-2 signaling pathway via interaction with TAF6 in U251 cells. Taken together, these findings suggest that the TAT-DCF1 peptide possesses great potential for the development of glioblastoma therapy through the interaction with TAF6-related pathways and provides further theoretic evidence for the mechanisms underlying the antitumor effects of TAT-DCF1.

Synthesis and photocatalytic activities of a CuO/TiO2 composite catalyst using aquatic plants with accumulated copper as a template.

A CuO/TiO2 composite photocatalyst was synthesized by using a hydrolysis method. In the synthesis of the CuO/TiO2 composite catalyst, the aquatic plant Eichhornia crassipes containing accumulated copper was used and combined with titanium chloride precursor. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Vis diffuse spectroscopy (DRS), and N2 adsorption-desorption isotherms were used for CuO/TiO2 characterization. The results showed that the CuO/TiO2 synthesized with Eichhornia crassipes as a template had smaller crystallite size (12.6 nm), higher specific surface area (109 m2 g-1), and higher pore volume (0.135 cm3 g-1). The catalytic activity of the CuO/TiO2 composite catalyst was also investigated by the degradation of phenol under ultraviolet (UV) and visible light irradiation, showing excellent catalytic activity. Complete removal of phenol was achieved at 80 and 120 min under UV and visible light sources, respectively. The catalytic performances may be due to the higher porosity and surface area of the composite catalyst. The Eichhornia crassipes aquatic plant also controls the crystal growth and prevents aggregation, which could enhance the catalytic activity. Moreover, the formation of the p-n CuO/TiO2 heterojunction also facilitates the separation of electrons and holes, and improves the photocatalytic activity of the material.

Interaction of DCF1 with ATP1B1 induces impairment in astrocyte structural plasticity via the P38 signaling pathway.

Astrocytes are known to regulate and support neuronal and synaptic functions. Changes in their size and morphology in mouse models result in mental retardation. However, the mechanism underlying these morphological changes remains unclear. In the present study, abnormal astrocyte morphology was found in the mouse brain following knockout of dendritic cell factor 1 (Dcf1). Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an interaction between these two proteins, with asparagine residue 266 of ATP1B1 being required for the interaction with DCF1. Moreover, Dcf1 knockout in mice resulted in upregulation of ATP1B1 expression in the hippocampus. Furthermore, DCF1 interaction with ATP1B1 in astrocytes impaired their structural plasticity. Ultimately, Dcf1 knockout increased glutamate release. Mechanism exploration proposed that Dcf1 knockout led to significantly perturbed expression of AMPA receptors (AMPARs) and induced morphological changes in astrocytes through the P38 signaling pathway. Our data shed light on the possible mechanisms underlying changes in astrocyte morphology and provide new avenues for the exploration of proteins involved in glutamate release.

Kernel differential subgraph reveals dynamic changes in biomolecular networks.

Many major diseases, including various types of cancer, are increasingly threatening human health. However, the mechanisms of the dynamic processes underlying these diseases remain ambiguous. From the holistic perspective of systems science, complex biological networks can reveal biological phenomena. Changes among networks in different states influence the direction of living organisms. The identification of the kernel differential subgraph (KDS) that leads to drastic changes is critical. The existing studies contribute to the identification of a KDS in networks with the same nodes; however, networks in different states involve the disappearance of some nodes or the appearance of some new nodes. In this paper, we propose a new topology-based KDS (TKDS) method to explore the core module from gene regulatory networks with different nodes in this process. For the common nodes, the TKDS method considers the differential value (D-value) of the topological change. For the different nodes, TKDS identifies the most similar gene pairs and computes the D-value. Hence, TKDS discovers the essential KDS, which considers the relationships between the same nodes as well as different nodes. After applying this method to non-small cell lung cancer (NSCLC), we identified 30 genes that are most likely related to NSCLC and extracted the KDSs in both the cancer and normal states. Two significance functional modules were revealed, and gene ontology (GO) analyses and literature mining indicated that the KDSs are essential to the processes in NSCLC. In addition, compared with existing methods, TKDS provides a unique perspective in identifying particular genes and KDSs related to NSCLC. Moreover, TKDS has the potential to predict other critical disease-related genes and modules.

A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration.

Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network. The results verify that the genes identified in the computational signaling network are indeed regulated by TMEM30A during cell migration, indicating the effectiveness of our proposed method and shedding light on the regulatory mechanisms underlying tumor migration, which facilitates the understanding of the molecular basis of tumor invasion.