Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.

OBJECTIVE: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally. METHODS: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally. RESULT: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05). CONCLUSION: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.

LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology.

BACKGROUND: It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data. METHOD: Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison. RESULTS: Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group. CONCLUSION: The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.

Case Report: foetal gastroschisis with ideal pregnancy outcomes under multidisciplinary treatment management.

Background: Gastroschisis has increased in recent years, however, complicated gastroschisis is associated with higher mortality, as well as higher health care costs and disease burdens from short- and long-term complications. Case introduction: A woman aged 25 years old at 37 + 1 weeks gestation (gravida 2; para 0) was admitted to the hospital because of foetal gastroschisis. Targeted quaternary ultrasound performed at our hospital showed that 34 mm of the abdominal wall was interrupted continuously, an intestinal echo with a range of approximately 88 × 50 mm was seen bulging outwards the local area close to the intestinal wall showed a 34 × 23 m anecho, and the foetus was measuring 2 weeks smaller than expected. After MDT including the maternal-foetal medicine, ultrasound, paediatric surgery, neonatal intensive care unit (NICU), and anaesthesiology departments, caesarean section was performed at 37 + 2 weeks. A baby boy was delivered, the small intestine, large intestine and stomach were seen outside of the abdomen, the abdominal cavity was excluded from the defect on the right side of the umbilical cord, the mesentery was shortened, and the intestinal tube had obvious oedema After paediatric surgical discussion, silo bag placement and delayed closure was performed, the placement process was smooth. One week following silo placement, the abdominal contents had been fully reduced below the fascia following daily partial reductions of the viscera,and the second stage of the operation was performed under general anaesthesia. The newborn was successfully discharged from the hospital 20 days after the operation and was followed up, with good growth, normal milk intake and smooth bowel movements. Conclusions: The diagnosis and treatment of complicated gastroschisis needs to be carried out under multidisciplinary team treatment. Delivery by cesarean section after 37 weeks is feasible.Immediate postpartum surgery is possible, and the choice of surgical modality is determined by the child's condition, emphasizing that it should be performed without adequate sedation under anaesthesia. A standardized postoperative care pathway appropriate to risk should be developed to optimize nutritional support and antibiotic use, and standardized enteral feeding practices should be sought with long-term follow-up.

Expression and Clinical Significance of TIGIT in Primary Breast Cancer.

Purpose: The roles of T cell immunoreceptor with Ig and ITIM domains (TIGIT) in the diagnosis of primary breast cancer (PBC) are still unclear. This study was designed to investigate the expression of TIGIT in PBC patients, with an aim to analyze its diagnostic value in PBC. Patients and Methods: We first explore the expression of TIGIT in cancer patients based on TCGA database, and then we analyzed its correlation with clinicopathological features. Afterwards, we compared the protein and mRNA expressions of TIGIT in two BC cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell line (MCF-10A). Subsequently, 56 PBC female patients admitted to the Taizhou People's Hospital from October 2018 to June 2021 were included in this study. Flow cytometry was used to detect TIGIT level on peripheral blood CD3+ T cells of PBC patients and healthy controls. TIGIT expression in PBC tissues was detected by immunohistochemistry (IHC) and immunofluorescence staining. Results: TCGA database showed that compared with adjacent tissues, TIGIT was significantly upregulated in tumor tissues. High TIGIT expression was positively correlated with tumor stage and negatively correlated with recurrence free survival (RFS) and overall survival (OS). TIGIT level in BC cell lines, peripheral blood and tumor tissues of PBC patients was significantly higher than that of control (P < 0.05). TIGIT level was correlated with age (P < 0.05), rather than tumor size, pathological type, lymph node metastasis, ER, PR, HER-2, and P53. ROC curve showed that the optimal critical value of peripheral blood TIGIT for BC screening was 23.38%. Postoperative TIGIT level in peripheral blood was significantly decreased compared to the preoperative TIGIT level (P < 0.05). Conclusion: TIGIT was upregulated in PBC and was correlated with age. It may be a potential target for the diagnosis and immunotherapy of PBC.

Prognostic Significance of Chromogranin A Expression in the Initial and Second Biopsies in Metastatic Prostate Cancer.

Neuroendocrine differentiation (NED) characterized by the expression of neuroendocrine markers, such as chromogranin A (CgA), is frequently observed in advanced prostate cancer (PCa), the prognostic significance of which is still controversial. Here we specifically addressed the issue of the potential prognostic value of CgA expression in advanced-stage PCa patients with distant metastases and its change over time from metastatic hormone-sensitive (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC). CgA expression was assessed immunohistochemically in initial biopsies of mHSPC, as well as in second biopsies of mCRPC in sixty-eight patients, and its correlation with prognosis (together with conventional clinicopathologic parameters) was analyzed using the Kaplan-Meier method and Cox proportional hazard model. We found that CgA expression was an independent adverse prognostic factor for both mHSPC (CgA positivity ≥ 1%, HR = 2.16, 95% CI: 1.04-4.26, p = 0.031) and mCRPC (CgA ≥ 10%, HR = 20.19, 95% CI: 3.04-329.9, p = 0.008). CgA positivity generally increased from mHSPC to mCRPC and was a negative prognosticator. The assessment of CgA expression may help with the clinical evaluation of advanced-stage patients with distant metastases.

Over-expression of RRM2 predicts adverse prognosis correlated with immune infiltrates: A potential biomarker for hepatocellular carcinoma.

Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database. Methods: The RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA). Results: The RRM2 expression level in tumor tissues was higher than normal tissues (P <0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage (P <0.05), pathologic stage (P <0.05), tumor status (P <0.05), histologic grade (P<0.001), and AFP (P <0.001). HCC with higher RRM2 expression was positively associated with worse OS (overall survival), PFS (progression-free survival), and DSS (disease-specific survival). In the univariate analysis, the expression of RRM2, T stage, M stage, pathologic stage, and tumor status were negatively correlated with OS (P <0.05). Further analysis using multivariate Cox regression showed that tumor status (P<0.01) and RRM2 expression (P<0.05) were independent prognostic factors of OS in HCC. GO/KEGG analysis showed that the critical biological process (chromosome condensation and p53 signaling pathway) might be the possible function mechanism in promoting HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression samples, including PD-1 signaling, cell cycle, P27 pathway, and T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of CD8 T cells, Cytotoxic cells, DCs, Neutrophils, NK cells, and T helper cells (P <0.05). Conclusion: Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis.

Lithium-ion diffusion in the grain boundary of polycrystalline solid electrolyte Li6.75La3Zr1.5Ta0.5O12 (LLZTO): a computer simulation and theoretical study.

Lithium-ion diffusion ability in solid electrolytes is crucial for the performance and safety of lithium-ion batteries. However, the lithium-ion diffusion coefficient of Li6.75La3Zr1.5Ta0.5O12 (LLZTO) measured experimentally is much lower than that simulated theoretically because LLZTO exists widely in the polycrystalline form rather than in the single-crystal form. Herein, we focus on the construction of grain boundaries in polycrystalline materials to address this key issue. An amorphous structure is created by randomly throwing atoms into a virtual box, where the chemical bonds are broken and rearranged through continuous heating and annealing operations, resulting in a stable framework structure. The lithium-ion diffusion coefficients of polycrystalline LLZTO and single-crystal LLZTO calculated via Ab initio molecular dynamics (AIMD) are consistent with the experimental data in trend. Furthermore, the analysis of the grain boundary composed of the secondary phase in polycrystalline LLZTO reveals that the continuous -O-M-O- metal oxide grid with low formation energy per atom restricts the lithium-ion migration. The lithium-ion migration barriers calculated utilizing density functional theory (DFT) also demonstrate the obstacle of the grain boundary from another perspective.

Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score.

BACKGROUND: Microwave ablation (MWA) is a potentially curative treatment for unresectable patients with hepatocellular carcinoma (HCC) ≤ 3 cm, while its therapeutic efficacy decreases significantly for HCC > 3cm. Previous studies have demonstrated that conventional transarterial chemoembolization (cTACE) combined with MWA (cTACE-MWA) may improve local tumor control rate and reduce the recurrence rate for HCC > 3cm. However, there have been few study designs to analyze the clinical efficacy of cTACE-MWA for medium-sized HCC (3-5cm). Therefore, this study aims to compare the clinical efficacy and safety of cTACE-MWA with cTACE alone for a single medium-sized HCC of 3-5 cm in diameter. METHODS: We retrospectively investigate the data of 90 patients with a single medium-sized HCC who were referred to our hospital and underwent cTACE-MWA or cTACE alone from December 2017 to March 2020. Then, patients were identified with propensity score-matched (1:1). The local tumor response to treatment and time to progression (TTP) were compared using mRECIST criteria between the cTACE-MWA group and the cTACE group. RESULTS: A total of 42 patients were included after matching (cTACE-MWA: 21; cTACE: 21). Comparing with cTACE, cTACE-MWA demonstrate significantly better local tumor control (ORR: 95.2% vs 61.9%, p = 0.02; DCR: 95.2% vs 66.7%, p = 0.045) and TTP (median 19.8 months vs 6.8 months, p < 0.001). The 1- and 2-year cumulative probabilities of OS were 100% and 95% in the cTACE-MWA group, which were significantly higher than those in the cTACE group (95% and 76%) (p = 0.032). Multivariate Cox regression analysis illustrates that cTACE-MWA was associated with better TTP (hazard ratio, 0.28; 95% CI: 0.1, 0.76; p = 0.012), but tumor size was associated with worse TTP (hazard ratio, 1.71; 95% CI: 1.01, 2.89; p = 0.045). CONCLUSIONS: cTACE followed by MWA improved TTP and OS in patients with a single medium-sized HCC, and no major complication was observed in this study.

Association of serum retinol concentration with normal-tension glaucoma.

OBJECTIVES: To evaluate the association between serum retinol concentration and normal-tension glaucoma (NTG). METHODS: A total of 345 study subjects were recruited in a prospective cross-sectional study: 101 patients with NTG, 106 patients with high-pressure primary open-angle glaucoma (POAG) and 138 healthy control subjects. Serum retinol concentration in fasting blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All study subjects were given complete ophthalmic examinations and diagnosed by two glaucoma sub-specialists. RESULTS: Serum retinol concentrations in NTG, POAG, and controls were 338.90 ± 103.23 ng/mL, 405.22 ± 114.12 ng/mL, and 408.84 ± 122.36 ng/mL respectively. NTG patients had lower serum retinol concentrations than POAG (p < 0.001) or healthy controls (p < 0.001). There was no statistical difference between the POAG and healthy controls (p = 0.780). Higher proportion of NTG patients (37.6%) than POAG (17.9%) or controls (21.7%) had serum retinol concentrations lower than 300 ng/mL. Serum retinol was positively correlated with optic nerve sheath diameter (ONSD) (r = 0.349, p = 0.001) in glaucoma patients and not associated with any other demographic features or ophthalmic biometric parameters in the NTG patients. Multivariate logistic regression showed that serum retinol (OR = 0.898, 95CI%: 0.851-0.947) was associated with incident NTG. CONCLUSIONS: NTG patients had lower serum retinol concentrations. Serum retinol uniquely associated with NTG makes it a new potential option for the diagnosis and treatment of the disease.

Readiness for hospital discharge and influencing factors: a cross-sectional study on patients discharged with tubes from the department of hepatobiliary surgery.

BACKGROUND: To investigate the readiness for hospital discharge of patients discharged with tubes from the department of hepatobiliary surgery and to explore the influencing factors. METHODS: A cross-sectional survey was conducted for the 161 patients with tubes who were discharged from the department of hepatobiliary surgery of Shaoxing Second Hospital by using the modified Chinese version of Readiness for Hospital Discharge Scale (RHDS) and Quality of Discharge Teaching Scale (QDTS). General data of the patients, such as gender, age, BMI (body mass index), and educational level, were collected. RESULTS: According to the statistical results, the total score of the RHDS was 142.40 ± 23.98, and that of the QDTS was 148.14 ± 17.74. Multiple linear step-wise regression analysis revealed that the total score of the QDTS, residence and educational level were the independent influencing factors of the readiness for hospital discharge (p < 0.05). CONCLUSION: The level of the readiness for hospital discharge of the 161 discharged patients with tubes from the department of hepatobiliary surgery was in the middle and lower level. For the patients who are far away from the hospital and have a low education level, we should pay more attention to health education and discharge teaching, so as to improve the readiness for hospital discharge of relatively vulnerable patients, reduce the incidence of adverse events after discharge with tubes, and ensure the health and safety of patients.

Diagnosis of hepatocellular carcinoma based on a terahertz signal and VMD-CWSE.

A novel strategy on combining variational mode decomposition (VMD) and composite weighted-scale sample entropy (CWSE) modified from composite multiscale entropy (CMSE) is proposed to screen hepatocellular carcinoma (HCC) by measuring the terahertz (THz) pulse signals of ten normal and ten HCC serums. Eight measured HCC specimens are negative in serum biomarker alpha fetoprotein (AFP) determination. In CWSE, the time series with weighted-scales are generated from the weighted average processing in the coarse-grained time series corresponding to each scale of the CMSE algorithm. VMD served as a preprocessing method was introduced into decomposing THz signal to obtain the mode functions of specific bandwidth for identification. Final results reveal that more obtainable entropy values of CWSE for recognition in comparison to those of CMSE on the basis of the rule of statistically significant difference and effect size and also manifest the stronger discriminability than the traditional THz parameters. This study provides a new potential auxiliary tool for diagnosis HCC and develops the methodology on the discrimination for similar THz signals.

Contribution of Digital Subtraction Angiogram in Diagnosis and Anatomic Recognition of Traumatic Pulsatile Mass.

Traumatic pulsating masses are difficult to make a definitive diagnosis due to anatomic variation of malformed vessels and rarely clinical incidence. It is essentially to recognizing the anatomy of such vessels, otherwise it may lead to an improperly treatment or serious complication. Digital subtraction angiogram (DSA) has a distinct advantage in both diagnosis and treatment of this subject. Here the authors report a case of venous malformation in the supraclavicular fossa with an underlying arteriovenous fistula following nonoperative management of a clavicle fracture in an adult, and discuss how to rule out potential differential diagnoses and get minimally invasive treatment with DSA.

Achieving Efficient Multichannel Conductance in Through-Space Conjugated Single-Molecule Parallel Circuits.

Constructing single-molecule parallel circuits with multiple conduction channels is an effective strategy to improve the conductance of a single molecular junction, but rarely reported. We present a novel through-space conjugated single-molecule parallel circuit (f-4Ph-4SMe) comprised of a pair of closely parallelly aligned p-quaterphenyl chains tethered by a vinyl bridge and end-capped with four SMe anchoring groups. Scanning-tunneling-microscopy-based break junction (STM-BJ) and transmission calculations demonstrate that f-4Ph-4SMe holds multiple conductance states owing to different contact configurations. When four SMe groups are in contact with two electrodes at the same time, the through-bond and through-space conduction channels work synergistically, resulting in a conductance much larger than those of analogous molecules with two SMe groups or the sum of two p-quaterphenyl chains. The system is an ideal model for understanding electron transport through parallel π-stacked molecular systems and may serve as a key component for integrated molecular circuits with controllable conductance.

A symbiotic hetero-nanocomposite that stabilizes unprecedented CaCl2-type TiO2 for enhanced solar-driven hydrogen evolution reaction.

Symbiotic hetero-nanocomposites prevail in many classes of minerals, functional substances and/or devices. However, design and development of a symbiotic hetero-nanocomposite that contains unachievable phases remain a significant challenge owing to the tedious formation conditions and the need for precise control over atomic nucleation in synthetic chemistry. Herein, we report a solution chemistry approach for a symbiotic hetero-nanocomposite that contains an unprecedented CaCl2-type titania phase inter-grown with rutile TiO2. CaCl2 structured TiO2, usually occurring when bulk rutile-TiO2 is compressed at an extreme pressure of several GPa, is identified to be a distorted structure with a tilt of adjacent ribbons of the c-axis of rutile. The structural specificity of the symbiotic CaCl2/rutile TiO2 hetero-nanocomposite was confirmed by Rietveld refinement, HRTEM, EXAFS, and Raman spectra, and the formation region (TiCl4 concentration vs. reaction temperature) was obtained by mapping the phase diagram. Due to the symbiotic relationship, this CaCl2-type TiO2 maintained a high stability via tight connection by edge dislocations with rutile TiO2, thus forming a CaCl2/rutile TiO2 heterojunction with a higher reduction capacity and enhanced charge separation efficiency. These merits endow symbiotic CaCl2/rutile TiO2 with a water splitting activity far superior to that of the commercial benchmark photocatalyst, P25 under simulated sunlight without the assistance of a cocatalyst. Our findings reported here may offer several useful understandings of the mechanical intergrowth process in functional symbiotic hetero-nanocomposites for super interfacial charge separation, where interfacial dislocation appears to be a universal cause.

8-Formylophiopogonanone B Antagonizes Paraquat-Induced Hepatotoxicity by Suppressing Oxidative Stress.

Flavonoids are some of the most important natural products with a variety of physiological activities. 8-Formylophiopogonanone B (8-FOB) is a naturally existing homoisoflavonoid in Ophiopogon japonicus. Paraquat (PQ) has been widely used as a potent herbicide and has high toxicity in humans. The goal of the present study was to investigate whether 8-FOB could protect against PQ-induced hepatotoxicity in vitro and in vivo. We first tested the protective effects of 8-FOB on PQ-induced cytotoxicity in L02 cells by determining cell viability, intracellular oxidative stress levels, mitochondrial function, and apoptosis in vitro. To verify the protective effects of 8-FOB, we pretreated mice with 8-FOB and assessed liver function, hepatic oxidative stress, and histopathological changes after PQ administration. Our results revealed that 8-FOB could antagonize PQ-induced hepatotoxicity in vitro and in vivo. The antagonistic effects could be attributed to suppressing oxidative stress, preserving mitochondrial function, and inhibiting apoptosis. The present study is the first to document that 8-FOB, a homoisoflavonoid compound, is an effective antioxidant for antagonizing PQ-induced hepatotoxicity.

Organic polymorphs with fluorescence switching: direct evidence for mechanical and thermal modulation of excited state transitions.

Herein, we provide a direct observation of the modulation of the excited state transition under mechanical and thermal stimuli in the solid state by two organic polymorphs based on a tetraphenylethene derivative (APMOB). It enriches the insight in the research of stimuli responsive luminescent materials.

Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress.

Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 µM α-LA significantly inhibited 1000 µM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨ m) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

Redox-responsive Fluorescent Nanoparticles Based on Diselenide-containing AIEgens for Cell Imaging and Selective Cancer Therapy.

A fluorescent, diselenide-containing 9,10-distyrylanthracene (DSA) derivative (SeDSA) with aggregation-induced emission (AIE) characteristic was successfully synthesized and SeDSA nanoparticles (NPs) were prepared through a nanoprecipitation method. SeDSA could coassemble with an antitumor prodrug, diselenide-containing paclitaxel (SePTX), which could be obtained by precipitation, to form SeDSA-SePTX Co-NPs (Co-NPs). Molecular dynamics (MD) simulations reveal that the driving forces for the self-assembly behaviors of SeDSA NPs and SePTX NPs are π-π interactions and hydrophobic interactions, respectively, while the driving forces for Co-NPs include hydrophobic interactions between SeDSA and SePTX, π-π interactions between SeDSA molecules and hydrophobic interactions between SePTX molecules. Meanwhile, Se-Se bonds play a crucial role in balancing the intramolecular forces. These diselenide-containing nanoparticles (SeDSA NPs, SePTX NPs and Co-NPs) exhibit a high stability under physiological conditions and excellent reduction-sensitivity in the presence of the redox agent glutathione (GSH) because of the selenium-sulfur exchange reaction between diselenide and GSH. Both SeDSA NPs and Co-NPs show strong orange fluorescence emissions on the account of the AIE feature of SeDSA and they were easily internalized by HeLa and HepG2 cells. Distinctively, the Co-NPs combine the advantage of SeDSA and SePTX for cell imaging and antineoplastic activity, and exhibit selectivity of cytotoxicities between neoplasia cells and normal cells. This study highlights the development of diselenide-containing AIEgens as a unique approach to prepare uniform and stable fluorescent nanoparticles for the application in cell imaging and tumor treatment.

Positive Connectivity Predicts the Dynamic Intrinsic Topology of the Human Brain Network.

Functional connectivity MRI (fcMRI) has become instrumental in facilitating research of human brain network organization in terms of coincident interactions between positive and negative synchronizations of large-scale neuronal systems. Although there is a common agreement concerning the interpretation of positive couplings between brain areas, a major debate has been made in disentangling the nature of negative connectivity patterns in terms of its emergence in several methodological approaches and its significance/meaning in specific neuropsychiatric diseases. It is still not clear what information the functional negative correlations or connectivity provides or how they relate to the positive connectivity. Through implementing stepwise functional connectivity (SFC) analysis and studying the causality of functional topological patterns, this study aims to shed light on the relationship between positive and negative connectivity in the human brain functional connectome. We found that the strength of negative correlations between voxel-pairs relates to their positive connectivity path-length. More importantly, our study describes how the spatio-temporal patterns of positive connectivity explain the evolving changes of negative connectivity over time, but not the other way around. This finding suggests that positive and negative connectivity do not display equivalent forces but shows that the positive connectivity has a dominant role in the overall human brain functional connectome. This phenomenon provides novel insights about the nature of positive and negative correlations in fcMRI and will potentially help new developments for neuroimaging biomarkers.