PFOS Exposure Promotes Hepatotoxicity in Quails by Exacerbating Oxidative Stress and Inflammation-Induced Apoptosis through Activating TLR4/MyD88/NF-κb Signaling.

PFOS is a ubiquitous pollutant garnering considerable attention due to its deleterious effects on both human and animal health. Given the poultry industry's intimate link with human health, investigating PFOS's impact on quails is crucial. PFOS readily accumulates in the liver, causing hepatotoxicity, yet its molecular mechanisms remain elusive. In our study, we fed quail diets contaminated with varying PFOS concentrations (12.5, 25, and 50 mg/kg) and observed dose-dependent liver damage in quails. The results show that PFOS damages mitochondrial structure, increases ROS levels, and downregulates antioxidants to promote oxidative stress damage in hepatocytes. PFOS also upregulated pro-inflammatory molecules (TNF-α, IL-1ß, and IL-6) while downregulating the anti-inflammatory factor IL-10, activating the TLR4//MyD88/NF-κB signaling pathway, thereby potentiating liver inflammation. Then, oxidative stress and inflammation by PFOS induce apoptosis in quail hepatocytes through the mitochondrial pathway, with severity closely related to hepatotoxicity. In conclusion, PFOS induces mitochondrial apoptosis by exacerbating oxidative stress and inflammation by activating the TLR4/MyD88/NF-κB signaling pathway, ultimately leading to hepatotoxicity in quails.

Chlorine-induced Gas-Solid coupled corrosion behaviors of tube materials in high steam parameter MSW incinerator.

The fast development of the waste incineration industry requires deeper insights into heating surface corrosion behavior at higher operating parameters with complex corrosion sources. This research investigates the corrosion behaviors of three types of plates, namely SA210-C, TP310, and 12CrMoV, when subjected to simulated flue gas and fly ash deposition simultaneously at temperatures ranging from 500℃ to 620℃. The results indicate that the weight loss due to coupling corrosion was 2.5 to 84.5 times higher than that of gas-phase corrosion under the same operating conditions. Among the three stainless-steels, TP310 demonstrates superior corrosion resistance. It is worth noting that, under the gas-solid coupling corrosion conditions, we observed a distinct two-layer structure of corrosion products. Despite the fly ash simulants detaching over time, the two-layer structure remained unchanged. Based on the theory of eutectic molten salt formation, we propose that alkali metal chlorides only initiate the formation of the molten layer in the initial stage of corrosion. Furthermore, we offer additional suggestions for the mechanism of sustaining the molten layer in the absence of alkali metal chlorides.

Enhanced electrocatalytic removal of bisphenol a by introducing Co/N into precursor formed from phenolic resin waste.

Bisphenol A (BPA) is a typical endocrine disruptor, which can be used as an industrial raw material for the synthesis of polycarbonate and epoxy resins, etc. Recently, BPA has appeared on the list of priority new pollutants for control in various countries and regions. In this study, phenolic resin waste was utilized as a multi-carbon precursor for the electrocatalytic cathode and loaded with cobalt/nitrogen (Co/N) on its surface to form qualitative two-dimensional carbon nano-flakes (Co/NC). The onset potentials, half-wave potentials, and limiting current densities of the nitrogen-doped composite carbon material Co/NC in oxygen saturated 0.5 mol H2SO4 were -0.08 V, -0.61 V, and -0.41 mA cm-2; and those of alkaline conditions were -0.65 V, -2.51 V, and -0.38 mA cm-2, and the corresponding indexes were improved compared with those of blank titanium electrodes, which indicated that the constructed nitrogen-doped composite carbon material Co/NC was superior in oxygen reduction ability. The catalysis by metallic cobalt as well as the N-hybridized active sites significantly improved the efficiency of electrocatalytic degradation of BPA. In the electro-Fenton system, the yield of hydrogen peroxide generated by cathodic reduction of oxygen was 4.012 mg L-1, which effectively promoted the activation of hydroxyl radicals. The removal rate of BPA was above 95% within 180 min. This work provides a new insight for the design and development of novel catalyst to degrade organic pollutants.

Co-utilization of carbon sources in microorganisms for the bioproduction of chemicals.

Carbon source is crucial for the cell growth and metabolism in microorganisms, and its utilization significantly affects the synthesis efficiency of target products in microbial cell factories. Compared with a single carbon source, co-utilizing carbon sources provide an alternative approach to optimize the utilization of different carbon sources for efficient biosynthesis of many chemicals with higher titer/yield/productivity. However, the efficiency of bioproduction is significantly limited by the sequential utilization of a preferred carbon source and secondary carbon sources, attributed to carbon catabolite repression (CCR). This review aimed to introduce the mechanisms of CCR and further focus on the summary of the strategies for co-utilization of carbon sources, including alleviation of CCR, engineering of the transport and metabolism of secondary carbon sources, compulsive co-utilization in single culture, co-utilization of carbon sources via co-culture, and evolutionary approaches. The findings of representative studies with a significant improvement in the bioproduction of chemicals via the co-utilization of carbon sources were discussed in this review. It suggested that by combining rational metabolic engineering and irrational evolutionary approaches, co-utilizing carbon sources can significantly contribute to the bioproduction of chemicals.

TERT mediates the U-shape of glucocorticoids effects in modulation of hippocampal neural stem cells and associated brain function.

BACKGROUND: Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient and excessive GCs impair these functions. Although this phenomenon could be explained by the U-shape of GC effects, the underlying mechanisms are still not clear. Therefore, understanding the underlying mechanisms of GCs may provide insight into the treatments for cognitive and mood-related disorders. METHODS: Consecutive administration of corticosterone (CORT, 10 mg/kg, i.g.) proceeded for 28 days to mimic excessive GCs condition. Adrenalectomy (ADX) surgery was performed to ablate endogenous GCs in mice. Microinjection of 1 µL of Ad-mTERT-GFP virus into mouse hippocampus dentate gyrus (DG) and behavioral alterations in mice were observed 4 weeks later. RESULTS: Different concentrations of GCs were shown to affect the cell growth and development of neural stem cells (NSCs) in a U-shaped manner. The physiological level of GCs (0.01 µM) promoted NSC proliferation in vitro, while the stress level of GCs (10 µM) inhibited it. The glucocorticoid synthesis blocker metyrapone (100 mg/kg, i.p.) and ADX surgery both decreased the quantity and morphological development of doublecortin (DCX)-positive immature cells in the DG. The physiological level of GCs activated mineralocorticoid receptor and then promoted the production of telomerase reverse transcriptase (TERT); in contrast, the stress level of GCs activated glucocorticoid receptor and then reduced the expression of TERT. Overexpression of TERT by AD-mTERT-GFP reversed both chronic stresses- and ADX-induced deficiency of TERT and the proliferation and development of NSCs, chronic stresses-associated depressive symptoms, and ADX-associated learning and memory impairment. CONCLUSION: The bidirectional regulation of TERT by different GCs concentrations is a key mechanism mediating the U-shape of GC effects in modulation of hippocampal NSCs and associated brain function. Replenishment of TERT could be a common treatment strategy for GC dysfunction-associated diseases.

Pediatric Ocular Myasthenia Gravis: Single-Center Experience.

BACKGROUND: Currently, there is no universally accepted standard treatment for ocular myasthenia gravis (OMG) in children. We aimed to investigate the possible proper regimens and timing of treatment for pediatric OMG cases based on the clinical manifestations: OMG with ptosis only and OMG with other features. METHODS: One hundred and forty two OMG cases attended at the Department of Pediatrics, Xiangya Hospital, Central South University, from 2010 to 2019 were included, and information from medical records was reviewed and recorded. Comparisons of clinical characteristics between patients with OMG with ptosis only and patients with OMG with other features as well as between patients treated with glucocorticoid (GC) within or after six months from disease onset were performed. RESULTS: OMG with other features constituted about 54.9% of the cases, and 66.2% of the patients achieved optimal outcome. Patients with OMG with ptosis only responded to pyridostigmine alone more than patients with OMG with other features who required several therapies (P < 0.001). Patients with OMG with ptosis only had a larger proportion of optimal outcome than the patients with OMG with other features (P = 0.002), and the difference remained significant even when the individual outcome groups were compared (P < 0.001). Patients who received GC within six months had a greater proportion of optimal outcome than those who received it after six months (P < 0.001). CONCLUSIONS: Although OMG with other features is a more common subtype of OMG, it is also more severe than OMG with ptosis only. An earlier addition of GC leads to optimal outcome.

Correlation between functional drainage and survival in malignant biliary obstruction after percutaneous biliary drainage.

Purpose: Malignant biliary obstruction (MBO) is common in patients with advanced malignant tumors, leading to poor prognosis and hindering antitumor therapy. The purpose of our study was to assess the survival outcomes for patients under therapy after percutaneous transhepatic biliary drainage (PTBD) and identify prognostic factors associated with survival in patients with MBO. Methods: From July 2010 to February 2021, 269 patients with MBO secondary to malignant tumor were divided into two groups (functional success and non-functional success). Survival time and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. Results: The overall median survival time after PTBD was 4.6 months (95 % IC:3.9-5.3). The 3- and 6-month survival rates were 68.0 % and 38.7 %, respectively. The median survival improved from 3.2 months to 8.4 months when the procedure achieved functional success. Multivariate analysis demonstrated that functionally successful drainage and antitumor treatment after PTBD were independent positive prognostic factors, but the total bilirubin after drainage and tumor size were independent negative predictive values. Conclusions: Functionally successful drainage could prolong survival time in patients with malignant biliary obstruction. Palliative care after drainage can prolong patient survival and improve their quality of life.

Using machine learning to trace the pollution sources of disinfection by-products precursors compared to receptor models.

To increase the efficiency of managing backup water resources, it is critical to identify and allocate pollution sources. Source apportionment of dissolved organic matter (DOM) was investigated in our work. Parallel factor analysis (PARAFAC) and the Spearman correlation analysis were used for source identification. After that, a newly hybrid model applying the fuzzy c-means and support vector regression (FCM-SVR) was employed for source apportionment compared to receptor models. The results demonstrated that the FCM-SVR model exhibited excellent generalization, and only required standardization and normalization as pre-processing steps for dataset. According to the results, microbial sources played a key role (28.1 %) in the formation potential of disinfection byproducts (DBPFPs). Additionally, shipping marine sources exhibited a substantial contribution (21.2 %) to DBPFPs. The prediction accuracy of DBPFPs was matched or exceeded receptor models, and the R2 of DOC (0.884) was significantly high. Therefore, we recommend the FCM-SVR model combined with PARAFAC to trace the source of DBPFPs as its significant effectiveness in source identification, source apportionment, and prediction accuracy, possessing the potential for further applicability in tracking more organic compounds. ENVIRONMENTAL IMPLICATION: The disinfection byproducts precursors in water sources, which were thought to be hazardous materials in this study, are proved to be chlorinated into carcinogenic disinfection byproducts (DBPs) during drinking water treatment, However, the source apportionment methods of DBPs are not well developed compared to other inorganic matter, e.g., heavy metals and ammonia nitrogen. We proposed a new FCM-SVR model to trace the source of DBPs, which required easier pre-treatment and resulted a better source apportionment and prediction accuracy. As a result, it could provide a different prospect and useful management advices to trace the source of DBPs.

Enhanced 2-MIB degradation by UV-LED/chlorine process: reaction kinetics, wavelength dependence, influencing factors and degradation pathways.

The efficient removal of 2-Methylisoborneol (2-MIB), a typical odour component, in water treatment plants (WTPs), poses a great challenge to conventional water treatment technology due to its chemical stability. In this study, the combination of ultraviolet light-emitting diode (UV-LED) and chlorine (UV-LED/chlorine) was exploited for 2-MIB removal, and the role of ultraviolet (UV) wavelength was investigated systematically. The results showed that UV or chlorination alone did not degrade 2-MIB effectively, and the UV/chlorine process could degrade 2-MIB efficiently, following the pseudo-first-order kinetic model. The 275 nm UV exhibited higher 2-MIB degradation efficiency in this UV-LED/chlorine system than 254 nm UV, 265 nm UV and 285 nm UV due to the highest mole adsorption coefficient and quantum yield of chlorine in 275 nm UV. ·OH and ·Cl produced in the 275 nm UV/chlorine system played major roles in 2-MIB degradation. HCO3- and Natural organic matter (NOM), prevalent in water, consumed ·OH and ·Cl, thus inhibiting the 2-MIB degradation by UV-LED/chlorine. In addition, NOM and 2-MIB could form a photonic competition effect. The degradation of 2-MIB by UV-LED/chlorine was done mainly through dehydration and demethylation, and odorous intermediates, such as camphor, were produced. 2-MIB was degraded through the α bond fracture and six-membered ring opening to form saturated or unsaturated hydrocarbons and aldehydes. Four DBPs, chloroform (CF), trichloroacetaldehyde (TCE), trichloroacetone (TCP) and dichloroacetone (DCP), were mainly generated, and CF was the most significant by-product.

Comparison of four pre-oxidants coupled powdered activated carbon adsorption for odor compounds and algae removal: Kinetics, process optimization, and formation of disinfection byproducts.

Pre-oxidation and powdered activate carbon (PAC) are usually used to remove algae and odorants in drinking waterworks. However, the influence of interaction between oxidants and PAC on the treatment performance are scarcely known. This study systematically investigated the combination schemes of four oxidants (KMnO4, NaClO, ClO2, and O3) and PAC on the inactivation of Microcystis aeruginosa cells and removal of four frequently detected odorants in raw water (diethyl disulfide (DEDS), 2,2'-oxybis(1chloropropane) (DCIP), 2-methylisoborneol (2-MIB) and geosmin (GSM)). O3 showed highest pseudo-first-order removal rate for all four compounds and NaClO exhibited highest inactivation rates for the cell viability and Chlorophyll a (Chl-a). The Freundlich model fitted well for the adsorption of DEDS and DCIP by PAC. When treated by combined oxidation/PAC, the removal ratio of algae cells and odorants were lower (at least 1.6 times) than the sum of removal ratios obtained in oxidation or PAC adsorption alone. Among these four oxidants, the highest synchronous control efficiency of odorants (52 %) and algae (66 %) was achieved by NaClO/PAC. Prolonging the dosage time interval promoted the removal rates. The pre-PAC/post-oxidation processes possessed comparable efficiency for the removal of odorants and algae cells comparing with pre-oxidation/post-PAC process, but significantly inhibited formation of disinfection byproducts (DBPs), especially for the formation of C-DBPs (for NaClO and ClO2), bromate (for O3) and chlorate/chlorite (for ClO2). This study could provide a better understanding of improving in-situ operation of the combined pre-treatments of oxidation and PAC for source water.

Discovering Nature's shield: Metabolomic insights into green zinc oxide nanoparticles Safeguarding Brassica parachinensis L. from cadmium stress.

Heavy metal cadmium (Cd) hinders plants' growth and productivity by causing different morphological and physiological changes. Nanoparticles (NPs) are promising for raising plant yield and reducing Cd toxicity. Nonetheless, the fundamental mechanism of nanoparticle-interfered Cd toxicity in Brassica parachineses L. remains unknown. A novel ZnO nanoparticle (ZnO-NPs) was synthesized using a microalgae strain (Chlorella pyrenoidosa) through a green process and characterized by different standard parameters through TEM, EDX, and XRD. This study examines the effect of different concentrations of ZnO-NPs (50 and 100 mgL-1) in B. parachineses L. under Cd stress through ultra-high-performance liquid chromatography/high-resolution mass spectrometry-based untargeted metabolomics profiling. In the presence of Cd toxicity, foliar spraying with ZnO-NPs raised Cu, Fe, Zn, and Mg levels in the roots and/or leaves, improved seedling development, as demonstrated by increased plant height, root length, and shoot and root fresh weight. Furthermore, the ZnO-NPs significantly enhanced the photosynthetic pigments and changed the antioxidant activities of the Cd-treated plants. Based on a metabolomics analysis, 481 untargeted metabolites were accumulated in leaves under normal and Cd-stressed conditions. These metabolites were highly enriched in producing organic acids, amino acids, glycosides, flavonoids, nucleic acids, and vitamin biosynthesis. Surprisingly, ZnO-NPs restored approximately 60% of Cd stress metabolites to normal leaf levels. Our findings suggest that green synthesized ZnO-NPs can balance ions' absorption, modulate the antioxidant activities, and restore more metabolites associated with plant growth to their normal levels under Cd stress. It can be applied as a plant growth regulator to alleviate heavy metal toxicity and improve crop yield in heavy metal-contaminated regions.

miR397-LACs mediated cadmium stress tolerance in Arabidopsis thaliana.

Cadmium (Cd) is a non-essential heavy metal, assimilated in plant tissue with other nutrients, disturbing the ions' homeostasis in plants. The plant develops different mechanisms to tolerate the hazardous environmental effects of Cd. Recently studies found different miRNAs that are involved in Cd stress. In the current study, miR397 mutant lines were constructed to explore the molecular mechanisms of miR397 underlying Cd tolerance. Compared with the genetically modified line of overexpressed miR397 (artificial miR397, amiR397), the lines of downregulated miR397 (Short Tandem Target Mimic miR397, STTM miR397) showed more substantial Cd tolerance with higher chlorophyll a & b, carotenoid and lignin content. ICP-OES revealed higher cell wall Cd and low total Cd levels in STTM miR397 than in the wild-type and amiR397 plants.Further, the STTM plants produced fewer reactive oxygen species (ROS) and lower activity of antioxidants enzymes (e.g., catalase [CAT], malondialdehyde [MDA]) compared with amiR397 and wild-type plants after stress, indicating that silencing the expression of miR397 can reduce oxidative damage. In addition, the different family transporters' gene expression was much higher in the amiR397 plants than in the wild type and STTM miRNA397. Our results suggest that miR397 plays a role in Cd tolerance in Arabidopsis thaliana. Overexpression of miR397 could decrease Cd tolerance in plants by regulating the expression of LAC 2/4/17, changing the lignin content, which may play an important role in inducing different stress-tolerant mechanisms and protecting the cell from a hazardous condition. This study provides a basis to elucidate the functions of miR397 and the Cd stress tolerance mechanism in Arabidopsis thaliana.

HIV protease inhibitor saquinavir inhibits toll-like receptor 4 activation by targeting receptor dimerization.

OBJECTIVE: Toll-like receptor 4 (TLR4) is crucial in induction of innate immune response through recognition of invading pathogens or endogenous alarming molecules. Ligand-triggered dimerization of TLR4 is essential for the activation of NF-κB and IRF3 through MyD88- or TRIF-dependent pathways. Saquinavir (SQV), an FDA-approved HIV protease inhibitor, has been shown to attenuate the activation of NF-κB induced by HMGB1 by blocking TLR4-MyD88 association in proteasome independent pathway. This study aims to define whether SQV is an HMGB1-specific and MyD88-dependent TLR4 signaling inhibitor and which precise signaling element of TLR4 is targeted by SQV. MATERIALS AND METHODS: PMA differentiated human THP-1 macrophages or reconstituted HEK293 cells were pretreated with SQV before stimulated by different TLR agonists. TNF-α level was evaluated through ELISA assay. NF-κB activation was analyzed using NF-κB SEAP reporting system. The levels of MyD88/TRIF pathways-related factors were examined by immunoblot. TLR4 endocytosis was assessed by immunocytochemistry. TLR4 dimerization was determined using immunoprecipitation between different tagged TLR4 and an in silico molecular docking experiment was performed to explore the possible binding site of SQV on its target. RESULTS: Our data showed that SQV suppresses both MyD88- and TRIF-dependent pathways in response to lipopolysaccharide (LPS), a critical sepsis inducer and TLR4 agonist, leading to downregulation of NF-κB and IRF3. SQV did not suppress MyD88-dependent pathway triggered by TLR1/2 agonist Pam3csk4. In the only TRIF-dependent pathway, SQV did not alleviate IRF3 phosphorylation induced by TLR3 agonist Poly(I:C). Furthermore, dimerization of TLR4 following LPS or HMGB1 stimulation was decreased by SQV. CONCLUSION: We concluded that TLR4 receptor complex is one of the mammalian targets of SQV, and TLR4-mediated immune responses and consequent risk for uncontrolled inflammation could be modulated by FDA-approved drug SQV.

[Clinical and genetic analysis of a child with Mental retardation autosomal dominant 51].

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). METHODS: A child with MRD51 who was hospitalized at Guangzhou Women and Children's Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. CONCLUSION: The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.

Insight into mixed chlorine/chloramines conversion and associated water quality variability in drinking water distribution systems.

Mixed chlorine/chloramines are common in drinking water distribution systems (DWDSs); however, their transformation and impact on chemical and microbial characteristics are not well understood. We systematically investigated water quality parameters associated with mixed chlorine/chloramine species conversion in 192 samples (including raw, finished, and tap water) collected throughout the year in a city in East China. Various chlorine/chloramine species (free chlorine, monochloramine [NH2Cl], dichloramine [NHCl2], and organic chloramines [OC]) were detected in both chlorinated and chloraminated DWDSs. NHCl2 + OC increased with transport distance along the pipeline network. The maximum proportion of NHCl2 + OC in over total chlorine in tap water reached 66 % and 38 % from chlorinated and chloraminated DWDSs, respectively. Both free chlorine and NH2Cl showed a rapid decay in the water pipe systems, but NHCl2 and OC were more persistent. Correlations between chlorine/chloramine species and physicochemical parameters were established. Models for predicting the sum of chloroform/TCM, bromodichloromethane/BDCM, chlorodibromomethane/CBDM, and bromoform/TBM (THM4) (R2 = 0.56) and haloacetic acids (HAAs) (R2 = 0.65) exhibited greater accuracy based on machine learning tuned with chlorine/chloramine species, particularly NHCl2 + OC. The predominant bacterial communities in mixed chlorine/chloramine systems were those resistant to chlorine or chloramine such as proteobacteria. NH2Cl was the most significant explanatory factor (28.1 %) for the variation in microbial community assemblage in chloraminated DWDSs. Although residual free chlorine and NHCl2 + OC, accounted for a smaller proportion of chlorine species in chloraminated DWDSs, they played an essential role (12.4 % and 9.1 %, respectively) in the microbial community structure.

Electrochemical oxidation of chloramphenicol by modified Sm-PEG-PbO2 anodes: Performance and mechanism.

Chloramphenicol (CAP) is used extensively in industry and daily life, but its abuse has seriously affected the environment and public health. In this paper, a new composite PbO2 electrode was obtained through the modification Sm and polyethylene glycol (PEG), and an electrocatalytic oxidation technology of CAP degradation was investigated. The results showed that the catalytic degradation ability and industrial service life of the PEG-Sm-PbO2 composite electrode were significantly enhanced. Co-doping inhibited the growth of grains, resulting in the formation of refined pyramidal grains on the surface of the electrode, which increased the number of active spots. The industrial service life of the modified electrode was improved by 87.0%. In addition, the degradation effect under different conditions and mechanism of CAP were also explored. The optimal conditions for CAP degradation were explored, at which time the CAP degradation rate reached 99.1%. The degradation process was in accordance with the primary reaction kinetics, and the apparent rate constant of CAP at the PEG-Sm-PbO2 electrode was raised by 57.1% in comparison with the unmodified electrode, indicating that the modification facilitated the degradation of CAP in the electrode. Finally, two possible CAP degradation pathways were deduced. The results will provide technical support and a theoretical basis for the degradation of persistent organic pollutants.

Comparison of Clinical Outcomes, Risks, and Costs for 20,910 Donor In Vitro Fertilization and 16,850 Donor Artificial Insemination Treatment Cycles: A Retrospective Analysis in China.

PURPOSE: To evaluate the effectiveness of donor in vitro fertilization (IVF-D) and donor artificial insemination (AI-D) in clinical outcomes, risks, and costs. METHODS: This study analyzed the cycle changes and clinical outcomes in 20,910 IVF-D and 16,850 AI-D cycles between 2013 and 2021 in the Reproductive and Genetic Hospital of CITIC-Xiangya. A cost-effectiveness analysis was performed to evaluate the costs per couple and per live birth cycle in the two treatment groups. RESULTS: IVF-D had higher pregnancy and live birth rates than AI-D (p < 0.001). The cumulative pregnancy and live birth rates for three AI-D cycles were 41.01% and 32.42%, respectively, higher than the rates for one or two AI-D cycles. The multiple birth and birth defect rate of AI-D was lower than that of IVF-D significantly. IVF-D mean cost per couple was higher than that of AI-D (CNY32,575 vs. CNY11,062, p < 0.001), with a mean cost difference of CNY21,513 (95% confidence interval, CNY20,517-22,508). The mean costs per live birth cycle for IVF-D and AI-D were CNY49,411 and CNY31,246, respectively. CONCLUSION: AI-D is more cost-effective and poses a lower risk for infertility couples than IVF-D, and patients should undergo three AI-D cycles to obtain the highest success rate.

Network pharmacology and in vivo studies reveal the pharmacological effects and molecular mechanisms of Celastrol against acute hepatic injury induced by LPS.

Sepsis is currently the main factor of death in the ICU, and the liver, as an important organ of immunity and stable metabolism, can be acutely damaged during sepsis, and the mortality rate of patients with sepsis complicated by acute liver injury is greatly increased. Celastrol (CEL) is derived from the root bark of Tripterygium wilfordii Hook.f.. As a traditional Chinese medicine, CEL has anti-inflammatory, anti-cancer, anti-oxidant, and other biological activities. Obtain CEL and AHI intersection targets via database and construct protein-protein interaction (PPI) network by STRING. GO functional enrichment and KEGG pathway analyses were performed by R studio. Targets were finally selected to perform molecular docking simulations with CEL. In vivo experiments based on the model of AHI were established by intraperitoneal injection of Lipopolysaccharide (LPS) 4 h, and pre-treated with CEL (0.5 mg/kg, 1 mg/kg, 1.5 mg/kg). The results are as follows: 273 genes with the intersection of CEL and AHI were obtained, and GO and KEGG enrichment analysis were used to design the mechanism of inflammation, apoptosis, and oxidative stress-related injury. By constructing the PPI network selected top 10 targets are: STAT3, RELA, MAPK1, MAPK3, TP53, AKT1, HSP90AA1, JUN, TNF, MAPK14, predicted CEL protection AHI design related pathways of MAPK and PI3K/AKT-related signal pathways. In vivo experiments, CEL inhibited the activation of MAPK and PI3K/AKT related pathways, reduced inflammatory response, apoptosis, and oxidative stress, and significantly improved LPS-induced AHI. In summary, this study predicted the mechanisms involved in the protective effect of CEL on AHI through network pharmacology. In vivo, CEL inhibited MAPK and PI3K/AKT-related signaling pathways, and reduced inflammatory response, apoptosis, and oxidative stress to protect LPS-induced AHI.

Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway.

Esophageal squamous cell carcinoma (ESCC) is characterized by high morbidity and mortality. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered an aberrantly expressed circRNA (hsa_circ_0021727) in patients with ESCC. However, the mechanism of action of hsa_circ_0021727 in tumors is unclear. The present study aimed to investigate the biological role of hsa_circ_0021727 and its mechanism in ESCC progression. We screened for the expression of hsa_circ_0021727 in ESCC patients. Patients with ESCC with high expression of hsa_circ_0021727 had shorter survival than those with low expression. Hsa_circ_0021727 promoted the proliferation, invasion, and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAK1-binding protein 1 (TAB1). Upregulation of TAB1 can activate the nuclear factor kappa B (NFκB) pathway. Hsa_circ_0021727 promoted ESCC progression by activating TAB1/NFκB pathway by sponging miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 could promote the proliferation, invasion, and migration of ESCC cells. In short, hsa_circ_0021727 promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway. These findings might provide potential targets to treat ESCC.

Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor.

In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.