Stability and chemical bonding in a series of inverse sandwich actinide boride clusters (An2B8) with δ bonding.

An inverse sandwich structure has been computationally predicted for uranium boride and extended to the series of actinide elements (An) from Th to Cm. The electronic structure and chemical bonding of these novel compounds have been analyzed using density functional theory and multireference wave-function based methods. We report the trends in electronic structure and bonding for An2B8, and found that (d-π)π and (d-p)δ are the most important factors in the stability of An2B8. The (f-p)δ bond provides extra stabilization for Pa2B8 and U2B8, owing to the extensive interactions of An-B8-An, resulting in a short distance for the Pa-Pa and U-U bonds.

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

PURPOSE OF REVIEW: Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. RECENT FINDINGS: Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

A ratiometric, colorimetric fluorescent probe with a large emission shift for the rapid detection of diethyl chlorophosphate.

A new ratiometric and colorimetric probe (SWJT-16) based on the isophorone skeleton to detect diethyl chlorophosphite (DCP), a nerve agent mimic, was designed and synthesized. SWJT-16 underwent a nucleophilic substitution reaction with DCP in DMF, leading to a large emission shift (Δλem = 174 nm) accompanied by a significant color change from blue to yellow under visible light. All these changes occurred within 6 seconds, faster than those of most reported ratiometric fluorescent probes for DCP. Furthermore, SWJT-16 was successfully employed to monitor gaseous DCP.

The collaborative monitored natural attenuation (CMNA) of soil and groundwater pollution in large petrochemical enterprises: A case study.

A large in-service petrochemical enterprises in Northeast China was taken as the research object, and the Collaborative Monitored Natural Attenuation (CMNA) for soil and groundwater pollution was carried out to remedy combined pollution and reduce environmental risks. The pollutants distributions were obtained based on detailed regional investigation (Mar. 2019), and feature pollutants in soil and groundwater were then screened. The spatiotemporal variations of feature pollutants and relative microbial responses were explored during the CMNA process. Furthermore, the CMNA efficiency of the contaminated site at initial stage was evaluated by calculation of natural attenuation rate constant. The results showed that the feature pollutants in soil were 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) and petroleum hydrocarbons (C10∼C40), and the feature pollutant in groundwater was 1,2-dichloroethane (1,2-DCA). The concentrations of all feature pollutants decreased continuously during four years of monitoring. Feature pollutants played a dominant role in the variability of microbial species both in soil and groundwater, increasing the relative abundance of petroleum tolerant/biodegradation bacteria, such as Actinobacteria, Proteobacteria and Acidobacteriota. The average natural attenuation rate constant of 2,2',5,5'-TCB and C10∼C40 in soil was 0.0012 d-1 and 0.0010 d-1, respectively, meeting the screening value after four years' attenuation. The average natural attenuation rate constant of 1,2-DCA was 0.0004 d-1, which need strengthening measures to improve the attenuation efficiency.

Prognostic role of pretreatment 18F-FDG PET/CT and hematological parameters in relapsed/refractory Hodgkin lymphoma patients treated with immune checkpoint inhibitors and chemotherapy: a dual-center cohort study.

BACKGROUND: The combination of anti-programmed death-1 antibodies and chemotherapy is effective; however, there are no reliable outcome prediction factors. We investigated the prognostic factors based on 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) quantitative and hematological parameters to predict progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients treated with immune checkpoint inhibitors (ICIs) and chemotherapy. METHODS: This retrospective study included 31 patients who underwent 18F-FDG PET/CT before and during treatment. Pretreatment metabolic and hematological parameters were evaluated using Cox regression analysis to identify predictors of PFS. Based on the cut-off values calculated using the receiver operating characteristic (ROC) curve, patients were classified into low-, intermediate-, and high-risk groups. Kaplan-Meier curves and the log-rank test were used to compare survival differences between the groups. RESULTS: Cox multivariable analysis indicted that the treatment response based on Lactate dehydrogenase (LDH), Lugano classification and SUVmax were independent predictors of PFS (P = 0.004, 0.007 and 0.039, respectively). The optimal cut-off values for SUVmax and LDH were 11.62 and 258.5 U/L, respectively (P < 0.01). Survival curves showed that LDH ≥ 258.5U/L and SUVmax ≥ 11.62 were correlated to shorter PFS (P < 0.001, P = 0.003, respectively). The differences in PFS between the low-, intermediate-, and high-risk groups were statistically significant (P = 0.0043). CONCLUSION: In R/R cHL patients treated with ICIs and chemotherapy, Lugano classification, SUVmax, and LDH were significantly correlated with PFS. The combination of metabolic and hematological parameters predicts PFS and may help to improve patient selection.

Angiopoietin-like 4 promotes epidermal stem cell proliferation and migration and contributes to cutaneous wound re-epithelialization.

Proliferation and migration of epidermal stem cells (EpSCs) are essential for epithelialization during skin wound healing. Angiopoietin-like 4 (ANGPTL4) has been reported to play an important role in wound healing, but the mechanisms involved are not fully understood. Here, we investigate the contribution of ANGPTL4 to full-thickness wound re-epithelialization and the underlying mechanisms using Angptl4-knockout mice. Immunohistochemical staining reveals that ANGPTL4 is significantly upregulated in the basal layer cells of the epidermis around the wound during cutaneous wound healing. ANGPTL4 deficiency impairs wound healing. H&E staining shows that ANGPTL4 deficiency significantly reduces the thickness, length and area of the regenerated epidermis postwounding. Immunohistochemical staining for markers of EpSCs (α6 integrin and ß1 integrin) and cell proliferation (PCNA) shows that the number and proliferation of EpSCs in the basal layer of the epidermis are reduced in ANGPTL4-deficient mice. In vitro studies show that ANGPTL4 deficiency impedes EpSC proliferation, causes cell cycle arrest at the G1 phase and reduces the expressions of cyclins D1 and A2, which can be reversed by ANGPTL4 overexpression. ANGPTL4 deletion suppresses EpSC migration, which is also rescued by ANGPTL4 overexpression. Overexpression of ANGPTL4 in EpSCs accelerates cell proliferation and migration. Collectively, our results indicate that ANGPTL4 promotes EpSC proliferation by upregulating cyclins D1 and A2 expressions and accelerating the cell cycle transition from G1 to S phase and that ANGPTL4 promotes skin wound re-epithelialization by stimulating EpSC proliferation and migration. Our study reveals a novel mechanism underlying EpSC activation and re-epithelialization during cutaneous wound healing.

Retention effect and mode of capillary zone on the migration process of LNAPL pollutants based on experimental exploration.

Two-dimensional sand tank experiments were designed to investigate the retention process of the capillary zone during the migration of light non-aqueous phase liquid (LNAPL) pollutants. The fine sand and silt media experiments simulated the LNAPL migration process given a shallow point source leakage scenario. The results indicate that the LNAPL was retained in the capillary zone. A retention factor, based on the ratio of the change in the vertical migration velocity of the LNAPL front with time, was proposed to quantitatively characterize the retention effect. The retention factor and time satisfied the function of σ=A×exp(-kt). And the retention factor increased gradually with time, indicating the enhanced retention effect of capillary zone on the vertical migration of LNAPL. The concentration change rate was then used to investigate the LANPL redistribution process, which had a relationship with time of νc=B×ln(t)+C. The capillary zone could be divided from top to bottom into a weak retention zone (B > 0, vc < 0), a strong retention zone (B < 0), and a barrier zone (B > 0, vc > 0). The retention effect of capillary zone on LNAPL migration gradually strengthened during the vertical migration of LNAPL. In addition, the coefficient B had a relationship with the environmental factors (i.e., EC, pH, and ORP) of B=a×sin(b×α×ß×γ)c and the fitting coefficient R2 of the function was above 0.913 for both media, indicating a strong correlation between the LNAPL redistribution process and the key environmental factors.

A Turn-On and Colorimetric Probe Based on Isophorone Skeleton for Detecting Nerve Agent Mimic Diethyl Chlorophosphite.

A new turn-on probe (SWJT-20) based on isophorone fluorophore for the detection of nerve agent mimic diethyl chlorophosphite (DCP) was designed and synthesized. SWJT-20 could rapidly respond to DCP within 2 s using UV-Vis or fluorescent spectra, accompanied by a significant change in the solution color under visible light or UV light, which could be observed by the naked eyes. The detection limit of SWJT-20 to DCP was as low as 8.3 nM, which is lower than those of most reported fluorescent probes for DCP detection. Additionally, SWJT-20 could quantitatively measure DCP using ratio changes in A427/A645 in absorption spectra. Furthermore, facile paper as sensors with the visualization of colorimetric/fluorometric responses based on SWJT-20 has been fabricated. Notably, this probe could detect DCP vapor through gas diffusion experiments.

Thyroid Hormone Disruption by Organophosphate Esters Is Mediated by Nuclear/Membrane Thyroid Hormone Receptors: In Vitro, In Vivo, and In Silico Studies.

Earlier mechanistic studies of many prohibited flame retardants (FRs) highlighted their thyroid hormone-disrupting activity through nuclear thyroid hormone receptors (nTRs), whereas some alternative FRs such as organophosphate esters (OPEs) exerted weak nTR-disrupting effects. However, an increasing number of studies have revealed that OPEs also exert thyroid hormone-disrupting effects, and the underlying mechanism is unclear. Herein, the thyroid hormone-disrupting effects and mechanisms of 8 typical OPEs were investigated using integrated in vitro, in vivo, and in silico assays. All tested chemicals competitively bound to the membrane thyroid hormone receptor (mTR) [the 20% relative inhibitory concentration (RIC20): (3.5 ± 0.2) × 101 to (4.9 ± 1.0) × 107 nM], and Cl-OPEs and alkyl-OPEs had lower RIC20 values. In contrast, only 4 OPEs showed nTR antagonistic activities at higher concentrations [≥ (4.8 ± 0.8) × 103 nM]. Cl-OPEs and alkyl-OPEs preferentially interacted with mTR. Molecular docking illustrated that OPEs docked into mTRs, consistent with the competitive binding assay. In vivo analyses of zebrafish embryonic development confirmed that tris(1,3-dichloro-2-propyl) phosphate induced inappropriate expression of proteins, and these protein interactions might be associated with mTR according to the quantitative proteomic analysis. Based on the results, mTR might play a critical role in mediating the thyroid hormone-disrupting effects of OPEs.

Ibrutinib in Advanced Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Lower Risk of Hepatitis B Virus Reactivation.

INTRODUCTION: Therapy of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with drugs such as ibrutinib and rituximab is often associated with immune suppression, opportunistic infections, and reactivation of virus infections such as hepatitis B virus (HBV). This risk is especially important in geographical regions like Asia where many potential therapy recipients have HBV infection. Also, whether safety and efficacy of ibrutinib in Asians and Europeans with advanced CLL/SLL are similar is unknown. We determined the safety and efficacy of ibrutinib compared with rituximab in advanced CLL/SLL including persons with HBV infection. We compared outcomes with data published from trials in persons of European descent. METHODS: This is a post hoc analysis of a multicenter, phase-3 trial (NCT01973387). Subjects with advanced CLL/SLL were randomized 2:1 to receive ibrutinib, 420 mg/day, or rituximab, 500 mg/mE + 2, for 6 cycles. Subjects with resolved HBV infection were included. Endpoints were progression-free survival (PFS), overall response rate (ORR), survival, and adverse events including resolved HBV reactivation. RESULTS: 131 subjects received ibrutinib (N = 87) or rituximab (N = 44) including 53 with resolved HBV infection. Median follow-up was 31 months (95% confidence interval: 28, 32 months). ORR was 61% (50, 71%) versus 7% (2, 18%; p < 0.001). Median PFS was not reached in the ibrutinib cohort but must be >40 months versus 8 months (7, 9 months; p < 0.0001) in the rituximab cohort. Median survival was not reached but must be >40 months versus 27 months (17 months, NE; p = 0.0006). In multivariable analyses, receiving ibrutinib increased PFS (hazard rate [HR] for failure = 0.12 [0.06, 0.23]; p < 0.001) and decreased risk of death (HR = 0.31 [0.15, 0.63]; p < 0.001). Median duration of exposure to ibrutinib was significantly longer than exposure to rituximab (28 vs. 5 months). The safety profile of ibrutinib was consistent with that observed in previous studies with no new safety signal. No subject receiving ibrutinib had HBV reactivation versus 2 receiving rituximab, despite much greater use of drugs to prevent HBV reactivation in the rituximab cohort. Outcomes were like those reported in persons of European descent, except ORR which, was unreliably correlated with PFS in Asians. CONCLUSION: Ibrutinib is safe and effective in persons with advanced CLL/SLL and better than rituximab in all therapy outcomes including risk of HBV reactivation. Outcomes with ibrutinib in Chinese were like those reported in persons of predominately European descent.

Adsorption characteristics of strontium by bentonite colloids acting on claystone of candidate high-level radioactive waste geological disposal sites.

The bentonite colloid produced in the deep geological repository of high-level radioactive waste can directly affect the migration of radionuclide strontium when it acts on claystone. The adsorption characteristics of strontium were investigated on claystone with the presence or absence of bentonite colloids from the Suhongtu area of China. The effects of different influencing factors, such as pH and solid content, on the adsorption process were investigated by batch adsorption experiments, and spectroscopic techniques were used to characterize the samples before and after adsorption of strontium. The results show that the presence of bentonite colloids can promote the adsorption of strontium on claystone under alkaline conditions. and the general order kinetic model provided the best fit to the experimental data. Strontium is adsorbed on the surface of claystone and bentonite colloid by ion exchange and surface complexation. Most of the Sr2+ formed SrCO3 with CO32- after ion exchange with Ca2+ and Mg2+ in plagioclase and dolomite, and a small amount of Sr2+ was adsorbed by complexation with -OH, Al-O and Si-O. These results provide a scientific basis for predicting the migration of strontium in subsurface porous media and the siting of high-level radioactive waste repositories.

The accuracy and effectiveness of automatic pedicle screw trajectory planning based on computer tomography values: an in vitro osteoporosis model study.

BACKGROUND: Pedicle screw placement in patients with osteoporosis is a serious clinical challenge. The bone mineral density (BMD) of the screw trajectory has been positively correlated with the screw pull-out force, while the computer tomography (CT) value has been linearly correlated with the BMD. The purpose of this study was to establish an in vitro osteoporosis model and verify the accuracy and effectiveness of automated pedicle screw planning software based on CT values in this model. METHODS: Ten vertebrae (L1-L5) of normal adult pigs were randomly divided into decalcification and control groups. In the decalcification group, the vertebral bodies were decalcified with Ethylenediaminetetraacetic acid (EDTA) to construct an in vitro osteoporosis model. In the decalcification group, automatic planning (AP) and conventional manual planning (MP) were used to plan the pedicle screw trajectory on the left and right sides of the pedicle, respectively, and MP was used on both sides of the control group. CT values of trajectories obtained by the two methods were measured and compared. Then, 3D-printed guide plates were designed to assist pedicle screw placement. Finally, the pull-out force of the trajectory obtained by the two methods was measured. RESULTS: After decalcification, the BMD of the vertebra decreased from - 0.03 ± 1.03 to - 3.03 ± 0.29 (P < 0.05). In the decalcification group, the MP trajectory CT value was 2167.28 ± 65.62 Hu, the AP trajectory CT value was 2723.96 ± 165.83 Hu, and the MP trajectory CT value in the control group was 2242.94 ± 25.80 Hu (P < 0.05). In the decalcified vertebrae, the screw pull-out force of the MP group was 48.6% lower than that of the control group (P < 0.05). The pull-out force of the AP trajectory was 44.7% higher than that of the MP trajectory (P < 0.05) and reached 97.4% of the MP trajectory in the control group (P > 0.05). CONCLUSION: Automatic planning of the pedicle screw trajectory based on the CT value can obtain a higher screw pull-out force, which is a valuable new method of pedicle screw placement in osteoporotic vertebre.

Does MIS-TLIF or TLIF result in better pedicle screw placement accuracy and clinical outcomes with navigation guidance?

BACKGROUND: Although previous studies have suggested that navigation can improve the accuracy of pedicle screw placement, few studies have compared navigation-assisted transforaminal lumbar interbody fusion (TLIF) and navigation-assisted minimally invasive TLIF (MIS-TLIF). The entry point of pedicle screw insertion in navigation-assisted MIS-TLIF (NM-TLIF) may deviate from the planned entry point due to an uneven bone surface, which may result in misplacement. The purpose of this study was to explore the pedicle screw accuracy and clinical consequences of MIS-TLIF and TLIF, both under O-arm navigation, to determine which surgical method is better. METHODS: A retrospective study of 54 patients who underwent single-segment NM-TLIF or navigation-assisted TLIF (N-TLIF) was conducted. In addition to the patients' demographic characteristics, intraoperative indicators and complications, the Oswestry Disability Index (ODI) and visual analog scale (VAS) score were recorded and analyzed preoperatively and at the 1-, 6-, and 12-month and final postoperative follow-ups. The clinical qualitative accuracy and absolute quantitative accuracy of pedicle screw placement were assessed by postoperative CT. Multifidus muscle injury was evaluated by T2-weighted MRI. RESULTS: Compared with N-TLIF, NM-TLIF was more advantageous in terms of the incision length, intraoperative blood loss, drainage volume, time to ambulation, length of hospital stay, blood transfusion rate and analgesia rate (P < 0.05). The ODI and VAS scores for low back pain were better than those of N-TLIF at 1 month and 6 months post-surgery (P < 0.05). There was no significant difference in the clinical qualitative screw placement accuracy (97.3% vs. 96.2%, P > 0.05). The absolute quantitative accuracy results showed that the axial translational error, sagittal translational error, and sagittal angle error in the NM-TLIF group were significantly greater than those in the N-TLIF group (P < 0.05). The mean T2-weighted signal intensity of the multifidus muscle in the NM-TLIF group was significantly lower than that in the N-TLIF group (P < 0.05). CONCLUSIONS: Compared with N-TLIF, NM-TLIF has the advantages of being less invasive, yielding similar or better screw placement accuracy and achieving better symptom relief in the midterm postoperative recovery period. However, more attention should be given to real-time adjustment for pedicle insertion in NM-TLIF rather than just following the entry point and trajectory of the intraoperative plan.

Response of environmental factors to attenuation of toluene in vadose zone.

Contaminated groundwater migrates in reverse direction under capillary force in vadose zone, and the attenuation process of pollutant adsorption and microbial degradation changes the environment of vadose zone. In this study, the response of toluene to environmental factors during reverse migration and attenuation of toluene from aquifer to vadose zone was studied by column experiment and experimental data analysis. The changes of environmental factors, including potential of hydrogen (pH), dissolved oxygen (DO), and oxidation-reduction potential (ORP), and toluene concentration were monitored by soil column experiment under sterilized and non-sterilized conditions. The 16S rRNA molecular biological detection technology was used to quantitatively analyze the impact of microbial degradation on the environment. Finally, the correlation between environmental factors and concentration in the attenuation process of toluene in the vadose zone was quantitatively studied by Pearson Correlation Coefficient (PCC) and multivariate statistical equation. The results showed that pH was primarily affected by microbial degradation, and DO and ORP were primarily affected by both adsorption and microbial degradation. The attenuation of toluene was divided into two stages: adsorption dominated (0~26 d) and microbial degradation dominated (26~55 d). The degradation amounts of microorganisms at each position in the non-sterilized column from bottom to top were 9.37%, 55.34%, 68.64%, 75.70%, 66.03% and 42.50%. At the same time, the article proposes for the first time that there is an obvious functional relationship between environmental factors (DO, ORP, pH), time (t) and concentration (CToluene):CToluene=C0+A100t+Bα+Cß+D100γ, (α,ß,γ are the pH, DO and ORP of capillary water, respectively; A, B, C and D are all undetermined coefficients), R2 > 0.95. The results of this study may facilitate the use of simple and easy-to-obtain environmental factors to characterize the dynamic process of pollutant concentration changes.

Response relationship of environmental factors caused by toluene concentration during leaching of capillary zone.

Due to the leaching of capillary water, the petroleum pollutants initially trapped in vadose zone may migrate to lower aquifer, thus increasing the risk of groundwater pollution. In order to explore the effect of capillary leaching on toluene-contaminated soil and the relationship between toluene concentration (TC) and environmental factors (EFs) during the leaching process, the sterilized and non-sterilized soil column experiments were designed. The EFs were used to estimate TC. The results showed that the difference between leaching and volatilization rates directly determined the changing trend of toluene concentration in capillary water. The toluene concentration in the medium always showed decreasing trend due to leaching. The indigenous microbial community structure of the non-sterilized soil column was analyzed by 16S rRNA sequencing. It was found that indigenous microorganisms could degrade toluene after 33.0 days of acclimatation. The microbial population was dominated by bacteria, among them the Ellin6055 strain and Pseudomonas, Pseudoxanthomonas, Cupriavidus, Bdellovibrio, Sphingobium, Phenylobacterium, Ramlibacter, Bradyrhizobium, Shinella genera. The Pseudomonas was the most crucial bacterial genus that degraded toluene. Indigenous microbial degradation was the fundamental reason for strong response relationship. Furthermore, we suggested a relationship of function between environmental factors (pH, DO, ORP) and time (t) for toluene attenuation: C0+ln(eAtαBγCß)=CToluene, (α, ß, γ represent the pH, DO, and ORP in leaching capillary water, respectively; A, B, and C represent undetermined coefficients), and the fitting coefficient R2 > 0.950. This relationship can only characterize the attenuation process of capillary zone leaching on toluene. However, it may still be utilized to give a theoretical foundation for understanding the dynamic of pollutant concentration change processes under specific environmental factors.

Construction, application and validation of a new algorithm for determining light nonaqueous-phase liquid fluxes in unsaturated zones.

An analytical algorithm coupling free-phase migration, precipitation, and natural attenuation through volatilization and biodegradation (FPVB) was developed to calculate the flux of light nonaqueous-phase liquid (LNAPL) leaking from unsaturated zone to groundwater. Sandbox and soil column experiments were performed to identify the LNAPL migration characteristics and states to provide data to establish and verify FPVB algorithm. For free-phase migration, the Kinematic Oily Pollutant Transport (KOPT) model was used to determine LNAPL movement velocity and leakage time. The correlations of water saturation, residual LNAPL saturation and the cumulative dissolution ratio of residual LNAPL were described using an empirical formula for the precipitation leaching process. Equations for diesel volatilization kinetics and first order degradation were used to describe the natural attenuation processes. Coupling the algorithms for the different stages gave the final FPVB algorithm. The FPVB algorithm was used to describe the pollution situation at a real site, and the results were consistent with the actual situation. The FPVB algorithm could be used to quickly assess the scale and degree of pollution with little information on the parameters for the actual LNAPL leakage event.

[Cistanches tubulosa water extract protects the testis against cyclophosphamide-induced injury: Effect and mechanism].

OBJECTIVE: To investigate the protective effect of Cistanche tubulosa water extract (CTWE) against cyclophosphamide (CTX)-induced testis injury (TI) in mice and its action mechanism. METHODS: Thirty male mice were equally randomized into a normal control, a CTX-induced TI model control and a CTWE treatment group. After 7 days of adaptive feeding, the mice in the CTWE treatment group were treated intragastrically with CTWE at 10 g/kg/d, those in the normal control and TI model control groups with the same volume of normal saline qd all for 35 successive days, and those in the TI model control and CTWE treatment groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg/d at 7, 14, 21, 28 and 35 days. Then all the animals were weighed, blood samples collected, and their testes and epididymides harvested for detection of the serum T content, examination of semen quality, measurement of testis weight, observation of histopathological changes in the testis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the mRNA expressions of the genes related to the nuclear factor erythroid-2-related factor (Nrf2) signaling pathway. RESULTS: The mice in the TI model control group, compared with the normal controls, showed significant decreases in the body weight (ï¼»34.13 ± 1.56ï¼½ vs ï¼»47.08 ± 1.98ï¼½ g, P < 0.05), testis weight (ï¼»81.82 ± 10.61ï¼½ vs ï¼»148.50 ± 14.82ï¼½ mg, P < 0.05), sperm concentration (ï¼»32.60 ± 5.29ï¼½ vs ï¼»78.90 ± 7.95ï¼½ ×106/ml, P < 0.05), sperm motility (ï¼»45.20 ± 7.09ï¼½% vs ï¼»86.70 ± 5.64ï¼½%, P < 0.05), serum T content (ï¼»7.49 ± 1.03ï¼½ vs ï¼»15.93 ± 1.36ï¼½ ng/L, P < 0.05), and SOD level (ï¼»152.22 ± 10.66ï¼½ vs ï¼»356.10 ± 30.95ï¼½ U/mg prot, P < 0.05), but remarkable increases in the percentage of morphologically abnormal sperm (MAS) (ï¼»39.30 ± 7.36ï¼½% vs ï¼»14.40 ± 3.53ï¼½ %, P < 0.05) and MDA level (ï¼»54.91 ± 5.12ï¼½ vs ï¼»31.71 ± 3.57ï¼½ nmol/mg prot, P < 0.05). The animals treated with CTWE, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»40.67 ± 2.13ï¼½ vs ï¼»34.13 ± 1.56ï¼½ g, P<0.05), testis weight (ï¼»121.21 ± 17.38ï¼½ vs ï¼»81.82 ± 10.61ï¼½ mg, P<0.05), sperm concentration (ï¼»58.40 ± 9.94ï¼½ vs ï¼»32.60 ± 5.29ï¼½ ×106/ml, P < 0.05), sperm motility (ï¼»72.30 ± 7.51ï¼½ % vs ï¼»45.20 ± 7.09ï¼½ %, P < 0.05), serum T content (ï¼»10.89 ± 1.07ï¼½ vs ï¼»7.49 ± 1.03ï¼½ ng/L, P < 0.05) and SOD level (ï¼»217.69 ± 24.59ï¼½ vs ï¼»152.22 ± 10.66ï¼½ U/mg prot, P < 0.05), but decreased percentage of MAS (ï¼»22.20 ± 6.07ï¼½% vs ï¼»39.30 ± 7.36ï¼½%, P < 0.05) and MDA level (ï¼»36.41 ± 4.27ï¼½ vs ï¼»54.91 ± 5.12ï¼½ nmol/mg prot, P < 0.05). The mRNA expressions of Nrf2, HO-1 and NQO-1 in the testis tissue were significantly down-regulated in the TI model controls compared with those in the normal controls (P < 0.05), and remarkably up-regulated in the CTWE treatment group in comparison with those in the TI model group (P < 0.05), while that of Caspase3 markedly increased in the TI model controls (P< 0.05) and decreased in the CTWE treatment group (P < 0.05). Histopathologically, the testis tissue of the TI model controls showed indistinct outlines from the base of the seminiferous tubule to the lumen surface, with disarranged and reduced layers of spermatogenic cells and decreased number of sperm in the seminiferous tubules, while the structure of the spermatogenic tubules recovered almost to normal in the CTWE treatment group. CONCLUSION: Cistanches tubulosa water extract can effectively inhibit cyclophosphamide-induced testis injury by enhancing the activity of antioxidant enzyme and regulating the expressions of the Nrf2 signaling pathway-related genes.

Hepatic small extracellular vesicles promote microvascular endothelial hyperpermeability during NAFLD via novel-miRNA-7.

BACKGROUND: A recent study has reported that patients with nonalcoholic fatty liver disease (NAFLD) are more susceptible to coronary microvascular dysfunction (CMD), which may predict major adverse cardiac events. However, little is known regarding the causes of CMD during NAFLD. In this study, we aimed to explore the role of hepatic small extracellular vesicles (sEVs) in regulating the endothelial dysfunction of coronary microvessels during NAFLD. RESULTS: We established two murine NAFLD models by feeding mice a methionine-choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 16 weeks. We found that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent endothelial hyperpermeability occurred in coronary microvessels during both MCD diet and HFD-induced NAFLD. The in vivo and in vitro experiments proved that novel-microRNA(miR)-7-abundant hepatic sEVs were responsible for NLRP3 inflammasome-dependent endothelial barrier dysfunction. Mechanistically, novel-miR-7 directly targeted lysosomal associated membrane protein 1 (LAMP1) and promotes lysosomal membrane permeability (LMP), which in turn induced Cathepsin B-dependent NLRP3 inflammasome activation and microvascular endothelial hyperpermeability. Conversely, a specific novel-miR-7 inhibitor markedly improved endothelial barrier integrity. Finally, we proved that steatotic hepatocyte was a significant source of novel-miR-7-contained hepatic sEVs, and steatotic hepatocyte-derived sEVs were able to promote NLRP3 inflammasome-dependent microvascular endothelial hyperpermeability through novel-miR-7. CONCLUSIONS: Hepatic sEVs contribute to endothelial hyperpermeability in coronary microvessels by delivering novel-miR-7 and targeting the LAMP1/Cathepsin B/NLRP3 inflammasome axis during NAFLD. Our study brings new insights into the liver-to-microvessel cross-talk and may provide a new diagnostic biomarker and treatment target for microvascular complications of NAFLD.

Identification of Prognostic Related Hub Genes in Clear-Cell Renal Cell Carcinoma via Bioinformatical Analysis.

Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma (ccRCC) via bioinformatics analysis. Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database: GSE12606, GSE36895 and GSE66272. The differentially expressed genes were screened with GEO2R and J Venn online tools. Functional annotation including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to identify the possible function of the hub genes involved in prognosis of ccRCC. In protein protein interaction network (PPI network), the STRING online tool was used to visualize the network of the differentially expressed genes, and the core gene was selected by MCODE App in Cytoscape software. Finally, GEPIA Survival Plot was performed to assess genes associated with worse survival. Results We totally found 648 differentially expressed genes, including 222 up-regulated genes and 426 down-regulated genes. PPI network showed that in 28 up-regulated genes 7 (CCNE2, CDK1, CDC6, CCNB2, BUB1, TTK and PTTG1) enriched in cell cycle and 4 genes (CCNE2, CDK1, CCNB2 and RRM2) enriched in p53 signaling pathway. GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1, CCNB2, RRM2, BUB1, and PTTG1 had a worse survival. GEPIA Box Plot showed that BUB1, CCNB2, PTTG1, and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues (P<0.05). Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1, and RRM2might manifest a poor prognosis.

[Gene expression profiling of testicular seminoma via bioinformatical analysis].

OBJECTIVE: To investigate the differentially expressed genes related to the survival of testicular seminoma patients and the pathogenesis of the malignancy. METHODS: We obtained the gene expression profiling of testicular seminoma data set GSE8607 from the GEO database and differentially expressed genes in testicular seminoma using the GEO2R online tool. We performed GO and KEGG pathway enrichment via the DAVID website, screened testicular seminoma-related core genes using the STRING and Cytoscape software, and analyzed the survival rate and expression level associated with the core genes through the Kaplan Meier plotter and GEPIA websites. RESULTS: Totally, 591 differentially expressed genes were identified, of which 216 were up-regulated and mainly enriched in 23 biological processes, 8 cell components, 5 biological functions and 7 KEGG pathways, and the other 375 down-regulated and enriched only in the biological process, involving the formation and development of spermatozoa. Thirty-two core genes were obtained via PPI network analysis, including C1QB, CCL2, CCR2, GPR183, ELL, LAPTM5, NPY5R, CD28 and MMP9, which were closely related to the survival rate (P < 0.05), C1QB, CCL2, CCR2, SELL, LAPTM5, CD28 and MMP9, which were highly expressed in the testicular seminoma tissue (P < 0.05), and NPY5R, which was lowly expressed in the testicular seminoma tissue (P < 0.05). CONCLUSIONS: The 8 differentially expressed genes identified in the testicular seminoma tissue contribute to effective prediction of the survival rate of the patients as well as to the diagnosis, prevention and treatment of the disease and development of new anti-cancer drugs.