Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity.

To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.

Disruption of sirtuin 7 in zebrafish facilitates hypoxia tolerance.

SIRT7 is a member of the sirtuin family proteins with nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase activity, which can inhibit the activity of hypoxia-inducible factors independently of its enzymatic activity. However, the role of SIRT7 in affecting hypoxia signaling in vivo is still elusive. Here, we find that sirt7-null zebrafish are more resistant to hypoxic conditions, along with an increase of hypoxia-responsive gene expression and erythrocyte numbers, compared with their wildtype siblings. Overexpression of sirt7 suppresses the expression of hypoxia-responsive genes. Further assays indicate that sirt7 interacts with zebrafish hif-1αa, hif-1αb, hif-2αa, and hif-2αb to inhibit their transcriptional activity and mediate their protein degradation. In addition, sirt7 not only binds to the hypoxia responsive element of hypoxia-inducible gene promoters but also causes a reduction of H3K18Ac on these promoters. Sirt7 may regulate hypoxia-responsive gene expression through its enzymatic and nonenzymatic activities. This study provides novel insights into sirt7 function and sheds new light on the regulation of hypoxia signaling by sirt7.

Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance.

Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wild-type siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wild-type zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.

SET7 methylates the deubiquitinase OTUB1 at Lys 122 to impair its binding to E2 enzyme UBC13 and relieve its suppressive role on ferroptosis.

The deubiquitinating enzyme OTUB1 possesses canonical deubiquitinase (DUB) activity and noncanonical, catalytic-independent activity, which has been identified as an essential regulator of diverse physiological processes. Posttranslational modifications of OTUB1 affect both its DUB activity and its noncanonical activity of binding to the E2 ubiquitin-conjugation enzyme UBC13, but further investigation is needed to characterize the full inventory of modifications to OTUB1. Here, we demonstrate that SET7, a lysine monomethylase, directly interacts with OTUB1 to catalyze OTUB1 methylation at lysine 122. This modification does not affect DUB activity of OTUB1 but impairs its noncanonical activity, binding to UBC13. Moreover, we found using cell viability analysis and intracellular reactive oxygen species assay that SET7-mediated methylation of OTUB1 relieves its suppressive role on ferroptosis. Notably, the methylation-mimic mutant of OTUB1 not only loses the ability to bind to UBC13 but also relieves its suppressive role on Tert-Butyl hydroperoxide-induced cell death and Cystine starvation/Erastin-induced cellular reactive oxygen species. Collectively, our data identify a novel modification of OTUB1 that is critical for inhibiting its noncanonical activity.

Comparison of the diagnostic effectiveness of ultrasound imaging coupled with three mathematical models for discriminating thyroid nodules.

BACKGROUND: The overlapping nature of thyroid lesions visualized on ultrasound (US) images could result in misdiagnosis and missed diagnoses in clinical practice. PURPOSE: To compare the diagnostic effectiveness of US coupled with three mathematical models, namely logistic regression (Logistics), partial least-squares discriminant analysis (PLS-DA), and support vector machine (SVM), in discriminating between malignant and benign thyroid nodules. MATERIAL AND METHODS: A total of 588 thyroid nodules (287 benign and 301 malignant) were collected, among which 80% were utilized for constructing the mathematical models and the remaining 20% were used for internal validation. In addition, an external validation cohort comprising 160 nodules (80 benign and 80 malignant) was employed to validate the accuracy of these mathematical models. RESULTS: Our study demonstrated that all three models exhibited effective predictive capabilities for distinguishing between benign and malignant nodules, whose diagnostic effectiveness surpassed that of the TI-RADS classification, particularly in terms of true negative diagnoses. SVM achieved a higher diagnostic rate for malignant thyroid nodules (93.8%) compared to Logistics (91.5%) and PLS-DA (91.6%). PLS-DA exhibited higher diagnostic rates for benign thyroid nodules (91.9%) compared to Logistics (86.7%) and SVM (88.7%). Both the area under the receiver operating characteristic curve (AUC) values of PLS-DA (0.917) and SVM (0.913) were higher than that of Logistics (0.891). CONCLUSION: Our findings indicate that SVM had significantly higher rates of true positive diagnoses and PLS-DA exhibited significantly higher rates of true negative diagnoses. All three models outperformed the TI-RADS classification in discriminating between malignant and benign thyroid nodules.

Novel modified semi-carbonized fiber prepared using discarded clothes for derisking Cu(II) and Pb(II) contaminated water.

We report a novel modified semi-carbonized fiber (CF) prepared using cotton and acrylic clothes for derisking contaminated water to realize the resource utilization of discarded clothes in wastewater treatment. In this study, amphoteric and auxiliary modifiers were used to modify CFs for preparing amphoteric and amphoteric-auxiliary CFs. The basic physicochemical properties of different modified CFs were determined, and the microscopic morphology of modified CFs was detected. The isothermal adsorption characteristics of Cu(II) and Pb(II) on different modified CFs were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and material dose were compared. Physicochemical properties and microscopic morphology results proved that amphoteric and auxiliary modifiers were modified on the CF surface and changed the surface properties of CF. The adsorption capacities of Cu(II) and Pb(II) on modified CFs increased with the increase in equilibrium concentration of Cu(II) and Pb(II), and the isotherm was more suitable for Freundlich model fitting than that of the Langmuir model. The maximum adsorption capacities (qm) of Cu(II) and Pb(II) on different modified CFs were 60.72-81.26 mg/g and 102.58-161.72 mg/g, respectively, and presented the trend of amphoteric-auxiliary CFs > amphoteric CFs > CFs. Increasing pH and temperature and decreasing ionic strength and material dose were beneficial to Cu(II) and Pb(II) adsorption. The Cu(II) and Pb(II) adsorption process was a spontaneous, endothermic, and entropy-increasing reaction, and the adsorption rate was controlled by chemisorption. The adsorption amount of amphoteric-auxiliary CFs maintained about 65% of original materials after 3 times of regeneration. Electrostatic attraction, precipitation, complexation, and ion exchange were the main adsorption mechanisms. The cation exchange capacity and total pore volume of modified CFs were key to determining qm of Cu(II) and Pb(II).

EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1α is repressed by SET7-catalyzed lysine methylation.

Egg-laying defective nine 1 (EGLN1) functions as an oxygen sensor to catalyze prolyl hydroxylation of the transcription factor hypoxia-inducible factor-1 α under normoxia conditions, leading to its proteasomal degradation. Thus, EGLN1 plays a central role in the hypoxia-inducible factor-mediated hypoxia signaling pathway; however, the posttranslational modifications that control EGLN1 function remain largely unknown. Here, we identified that a lysine monomethylase, SET7, catalyzes EGLN1 methylation on lysine 297, resulting in the repression of EGLN1 activity in catalyzing prolyl hydroxylation of hypoxia-inducible factor-1 α. Notably, we demonstrate that the methylation mimic mutant of EGLN1 loses the capability to suppress the hypoxia signaling pathway, leading to the enhancement of cell proliferation and the oxygen consumption rate. Collectively, our data identify a novel modification of EGLN1 that is critical for inhibiting its enzymatic activity and which may benefit cellular adaptation to conditions of hypoxia.

Methyltransferase SMYD3 impairs hypoxia tolerance by augmenting hypoxia signaling independent of its enzymatic activity.

Hypoxia-inducible factor (HIF)1α, a main transcriptional regulator of the cellular response to hypoxia, also plays important roles in oxygen homeostasis of aerobic organisms, which is regulated by multiple mechanisms. However, the full cellular response to hypoxia has not been elucidated. In this study, we found that expression of SMYD3, a methyltransferase, augments hypoxia signaling independent of its enzymatic activity. We demonstrated SMYD3 binds to and stabilizes HIF1α via co-immunoprecipitation and Western blot assays, leading to the enhancement of HIF1α transcriptional activity under hypoxia conditions. In addition, the stabilization of HIF1α by SMYD3 is independent of HIF1α hydroxylation by prolyl hydroxylases and the intactness of the von Hippel-Lindau ubiquitin ligase complex. Furthermore, we showed SMYD3 induces reactive oxygen species accumulation and promotes hypoxia-induced cell apoptosis. Consistent with these results, we found smyd3-null zebrafish exhibit higher hypoxia tolerance compared to their wildtype siblings. Together, these findings define a novel role of SMYD3 in affecting hypoxia signaling and demonstrate that SMYD3-mediated HIF1α stabilization augments hypoxia signaling, leading to the impairment of hypoxia tolerance.

Ambient particulate air pollution, blood cell parameters, and effect modification by psychosocial stress: Findings from two studies in three major Chinese cities.

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 µg/m3 increment in PM2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM2.5 exposure.

Thrombin injection under B-flow and ultrasound guidance: A safe and effective treatment of pseudoaneurysms.

PURPOSE: To evaluate the method of thrombin injection under B-flow and ultrasound guidance (BUGTI) for the treatment of pseudoaneurysms. MATERIALS AND METHODS: Twenty-one patients suffering from pseudoaneurysm (PSA) were retrospectively reviewed at the First Affiliated Hospital of Nanjing Medical University in Nanjing, China, from January 2018 to August 2019. The patients were treated using an ultrasound-guided injection of thrombin (500 IU/mL) combined with B-mode blood flow imaging (B-flow). The information on the PSA, including the size of the arterial rupture and sac, flow rate, thrombin dose, and treatment outcome, was recorded during the procedure. Follow-up evaluation was performed at 1, 3, and 6 months after the treatment. Pearson's correlation analysis was performed among the characteristics of PSA and the dose of thrombin. RESULT: The age of patients ranged from 34 to 80 years and averaged 62.8 years. The maximum cross-sectional area of PSA ranged from 208 to 1148 mm2. All patients were treated with thrombin injections. The dose of thrombin ranged from 300 to 1667 IU. No reperfusions were detected at follow-up 6 months, and the BUGTI treatment was successful in all 21 cases. Pearson's correlation analysis demonstrated that the dose of thrombin was positively correlated with the width (r = 0.449, p < .05) and maximum cross-sectional area (r = 0.504, p < .05) of PSA. CONCLUSION: Thrombin injection under B-flow and ultrasound guidance is a rapid and effective treatment for PSA. Additionally, the sac size could be used to estimate the dose of thrombin.

Effect mechanism of litter extract from Alternanthera philoxeroides on the selective absorption of heavy metal ions by amphoteric purple soil.

Plant litter causes a serious waste of resources. Thus, plant litter extract (LE) should be used in the soil remediation of heavy metals. In this study, different proportions of LE from the Alternanthera philoxeroides were used to modify dodecyl dimethyl betaine (BS)-modified purple soil (P). The basic physicochemical properties of LE + BS-modified Ps (LE + BS-Ps) were determined, and the microscopic morphology of LE + BS-Ps was studied by using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, and specific surface area detection. The isothermal adsorption characteristics of heavy metal ions (Pb2+, Cu2+, and Cr6+) on different LE + BS-Ps were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and LE + BS-P's property were compared. Results showed that the cation exchange capacity and specific surface area of LE + BS-Ps increased, pH of LE + BS-Ps decreased, and TOC of LE + BS-Ps increased first and then decreased with increasing proportion of LE. FTIR, SEM, and EDS results proved that LE was modified on the surface of BS-P. Langmuir and Freundlich models could be used to describe the adsorption isotherms of heavy metal ions on different LE + BS-Ps, and the fitting correlation of the Langmuir model was higher than that of the Freundlich model. The maximum adsorption capacity (qm) of Pb2+, Cu2+, and Cr6+ were 107.60-295.66, 133.00-342.11, and 33.59-75.41 mmol/kg, respectively. The qm of Pb2+, Cu2+, and Cr6+ on LE + BS-Ps all increased first and then decreased with increasing proportion of LE, and the peak value was observed in 20%LE + BS-Ps. High pH improved Pb2+ and Cu2+ adsorption but inhibited Cr6+ adsorption. The adsorption amounts of Pb2+, Cu2+, and Cr6+ all increased first and then decreased with incresing ionic strength and were maintained at the maximum value of 0.1-0.2 mol/L. The Pb2+, Cu2+, and Cr6+ adsorption mechanisms on different LE + BS-Ps showed a positive temperature effect and presented spontaneous, exothermic and entropy-adding processes.

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kappaB signaling pathway in cerebral ischemia-reperfusion rats was explored. MATERIAL AND METHODS Ninety rats were randomly divided into 5 groups - a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex) - with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1ß, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and NF-kappaB. RESULTS Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2- and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kappaB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H2O2, MDA, NO, IL-1ß, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkappaBalpha was also detected. CONCLUSIONS Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kappaB signaling pathway.

Detection and characterization of a novel hepacivirus in long-tailed ground squirrels (Spermophilus undulatus) in China.

Rodent populations are known to be reservoirs of viruses with the potential to infect humans. However, a large number of such viruses remain undiscovered. In this study, we investigated the shedding of unknown viruses in long-tailed ground squirrel (Spermophilus undulatus) feces by high-throughput sequencing. A novel and highly divergent virus related to members of the genus Hepacivirus was identified in ground squirrel liver. This virus, tentatively named RHV-GS2015, was found to have a genome organization that is typical of hepaciviruses, including a long open reading frame encoding a polyprotein of 2763 aa. Sequence alignment of RHV-GS2015 with the most closely related hepaciviruses yielded p-distances of the NS3 and NS5B regions of 0.546 and 0.476, respectively, supporting the conclusion that RHV-GS2015 is a member of a new hepacivirus species, which we propose to be named "Hepacivirus P". Phylogenetic analysis of the NS3 and NS5B regions indicated that RHV-GS2015 shares common ancestry with other rodent hepaciviruses (species Hepacivirus E, and species Hepacivirus F), Norway rat hepacivirus 1 (species Hepacivirus G), and Norway rat hepacivirus 2 (species Hepacivirus H). A phylogenetic tree including the seven previously identified rodent hepaciviruses revealed extreme genetic heterogeneity among these viruses. RHV-GS2015 was detected in 7 out of 12 ground squirrel pools and was present in liver, lung, and spleen tissues. Furthermore, livers showed extremely high viral loads of RHV-GS2015, ranging from 2.5 × 106 to 2.0 × 108 copies/g. It is reasonable to assume that this novel virus is hepatotropic, like hepatitis C virus. The discovery of RHV-GS2015 extends our knowledge of the genetic diversity and host range of hepaciviruses, helping to elucidate their origins and evolution.

Alteration of occlusal vertical dimension induces signs of neuroplastic changes in corticomotor control of masseter muscles: Preliminary findings.

PURPOSE: To investigate the effect of altering occlusal vertical dimension (OVD) in patients with severe attrition on corticomotor control of the masseter muscles as assessed by navigated transcranial magnetic stimulation (nTMS). METHODS: Seven patients (58.6 ± 8.4 years) with decreased OVD due to severe attrition were given mandibular occlusal splints to alter the OVD with the instruction to wear during the whole awake time for a period of four weeks. Motor-evoked potentials (MEPs) and the motor cortex maps of the masseter muscles and first dorsal interosseous (FDI) muscles as control were recorded by nTMS at baseline and at least 4 weeks after the alteration of OVD. The stimulus-response curves of MEPs were analysed with two-way repeated-measures ANOVA, and the numerical rating scale scores, motor thresholds, onset latencies, motor cortex maps and centre of gravity (COG) were analysed with paired t tests. RESULTS: There was a significant increase in the amplitude of the masseter muscle MEPs (P = 0.036), but no change in the motor cortex map areas (P = 0.111) four weeks after the alteration of OVD. Furthermore, there was no significant difference in either the amplitude of the FDI muscle MEPs (P = 0.466) or the motor cortex map areas (P = 0.230) before and after OVD alteration. CONCLUSION: The results suggest that alteration of OVD in patients with severe attrition was associated with signs of neuroplastic changes in the corticomotor control of the masseter muscles. The results of the study may add to our understanding of the putative mechanisms related to cortical changes in response to OVD alterations.

Diverse novel astroviruses identified in wild Himalayan marmots.

With advances in viral surveillance and next-generation sequencing, highly diverse novel astroviruses (AstVs) and different animal hosts had been discovered in recent years. However, the existence of AstVs in marmots had yet to be shown. Here, we identified two highly divergent strains of AstVs (tentatively named Qinghai Himalayanmarmot AstVs, HHMAstV1 and HHMAstV2), by viral metagenomic analysis in liver tissues isolated from wild Marmota himalayana in China. Overall, 12 of 99 (12.1 %) M. himalayana faecal samples were positive for the presence of genetically diverse AstVs, while only HHMAstV1 and HHMAstV2 were identified in 300 liver samples. The complete genomic sequences of HHMAstV1 and HHMAstV2 were 6681 and 6610 nt in length, respectively, with the typical genomic organization of AstVs. Analysis of the complete ORF 2 sequence showed that these novel AstVs are most closely related to the rabbit AstV, mamastrovirus 23 (with 31.0 and 48.0 % shared amino acid identity, respectively). Phylogenetic analysis of the amino acid sequences of ORF1a, ORF1b and ORF2 indicated that HHMAstV1 and HHMAstV2 form two distinct clusters among the mamastroviruses, and may share a common ancestor with the rabbit-specific mamastrovirus 23. These results suggest that HHMAstV1 and HHMAstV2 are two novel species of the genus Mamastrovirus in the Astroviridae. The remarkable diversity of these novel AstVs will contribute to a greater understanding of the evolution and ecology of AstVs, although additional studies will be needed to understand the clinical significance of these novel AstVs in marmots, as well as in humans.

Effect of virtual reality distraction on pain among patients with hand injury undergoing dressing change.

AIMS AND OBJECTIVES: To assess the effect of virtual reality distraction on pain among patients with a hand injury undergoing a dressing change. BACKGROUND: Virtual reality distraction can effectively alleviate pain among patients undergoing a dressing change. Clinical research has not addressed pain control during a dressing change. DESIGN: A randomised controlled trial was performed. METHODS: In the first dressing change sequence, 98 patients were randomly divided into an experimental group and a control group, with 49 cases in each group. Pain levels were compared between the two groups before and after the dressing change using a visual analog scale. The sense of involvement in virtual environments was measured using the Pearson correlation coefficient analysis, which determined the relationship between the sense of involvement and pain level. RESULTS: The difference in visual analog scale scores between the two groups before the dressing change was not statistically significant (t = 0·196, p > 0·05), but the scores became statistically significant after the dressing change (t = -30·792, p < 0·01). The correlation between the sense of involvement in a virtual environment and pain level during the dressing was statistically significant (R(2) = 0·5538, p < 0·05). CONCLUSION: Virtual reality distraction can effectively alleviate pain among patients with a hand injury undergoing a dressing change. Better results can be obtained by increasing the sense of involvement in a virtual environment. RELEVANCE TO CLINICAL PRACTICE: Virtual reality distraction can effectively relieve pain without side effects and is not reliant on a doctor's prescription. This tool is convenient for nurses to use, especially when analgesics are unavailable.

Pb(II) and chlortetracycline immobilization and economy of biologically amended coastal soil.

To study the pollutants immobilization and economy of biologically amended coastal soil, Alternanthera philoxeroides biomass (Bm), biochar (Bc), and dodecyldimethyl betaine (BS) modified Bc (BS-Bc) were used to amend coastal soil from Jialing, Fu, and Qu River. A runoff experiment was used to simulate the longitudinal migration and morphological changes of Pb(II) and chlortetracycline (CTC) in each amended coastal soil, and the economy of pollutants immobilization by different amended coastal soil were compared. The equilibrium time of Pb(II) and CTC in each amended coastal soil ranked in the order of BS-Bc-amended > Bc-amended > Bm-amended > unamended coastal soil. The average Pb(II) and CTC flow rate in different amended coastal soils presented an opposite trend with the equilibrium time. Pb(II) and CTC content all reduced with the increasing runoff length. Under the same soils, the content changes presented Bm and Bc amended > unamended > BS-Bc amended. CEC and clay content of coastal soils were the key factors affecting Pb(II) and CTC immobilization. The immobilization mechanisms were electrostatic attraction, ion exchange, surface precipitation, and complexation to Pb(II) and ion exchange and complexation to CTC. The economy of Pb(II) and CTC immobilization ranged from 0.5 to 9.0 and from 1.0 to 5.4 mg/¥, and coastal soil amended by BS-Bc had practical application value and high economy.

Inhibiting neddylation with MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells.

Hypoxia, an inadequate supply of tissue oxygen tension, has been reported to induce apoptosis of spermatogenic cells and is associated with male infertility. Neddylation, a post-translational modification similar to ubiquitination, has been shown to be involved in the hypoxia stress response. However, the functions of neddylation in hypoxia-induced apoptosis of spermatogenic cells and its association with male infertility remain largely unexplored. In this study, aiming to explore the role of neddylation in male infertility, we used the specific neddylation inhibitor MLN4924 for treatment in mouse type B spermatogonia GC-2 cells. Our results showed that MLN4924 had no apparent effect on GC-2 cell apoptosis under normoxia, but significantly increased apoptotic cells under hypoxia. Transcriptomic analysis and qPCR assay confirmed that MLN4924 could suppress the expression of hypoxia target genes in GC-2 cells under hypoxia. In addition, MLN4924 could enhance the induction of intracellular and mitochondrial reactive oxygen species (ROS) under hypoxia. These results indicate that the neddylation inhibitor MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells, and neddylation may play an important role in promoting spermatogenic cells to adapt to hypoxia stress.

Application of ultrasound elastography and radiomic for predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma.

Objective: This study aims to combine ultrasound (US) elastography (USE) and radiomic to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: A total of 204 patients with 204 thyroid nodules who were confirmed with PTMC and treated in our hospital were enrolled and randomly assigned to the training set (n = 142) and the validation set (n = 62). US features, USE (gender, shape, echogenic foci, thyroid imaging reporting and data system (TIRADS) category, and elasticity score), and radiomic signature were employed to build three models. A nomogram was plotted for the combined model, and decision curve analysis was applied for clinical use. Results: The combined model (USE and radiomic) showed optimal diagnostic performance in both training (AUC = 0.868) and validation sets (AUC = 0.857), outperforming other models. Conclusion: The combined model based on USE and radiomic showed a superior performance in the prediction of CLNM of patients with PTMC, covering the shortage of low specificity of conventional US in detecting CLNM.

Analysis of early response to chemotherapy for non-Hodgkin's lymphoma by quantitative contrast-enhanced ultrasound: A prospective case-control crossectional study.

OBJECTIVE: To investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin's lymphoma (NHL). METHODS: Fifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters. RESULTS: After three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001). CONCLUSIONS: CEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.