ConvMedSegNet: A multi-receptive field depthwise convolutional neural network for medical image segmentation.

In order to achieve highly precise medical image segmentation, this paper presents ConvMedSegNet, a novel convolutional neural network designed with a U-shaped architecture that seamlessly integrates two crucial modules: the multi-receptive field depthwise convolution module (MRDC) and the guided fusion module (GF). The MRDC module's primary function is to capture texture information of varying sizes through multi-scale convolutional layers. This information is subsequently utilized to enhance the correlation of global feature data by expanding the network's width. This strategy adeptly preserves the inherent inductive biases of convolution while concurrently amplifying the network's ability to establish dependencies on global information. Conversely, the GF module assumes responsibility for implementing multi-scale feature fusion by connecting the encoder and decoder components. It facilitates the transfer of information between features that are separated over substantial distances through guided fusion, effectively minimizing the loss of critical data. In experiments conducted on public medical image datasets such as BUSI and ISIC2018, ConvMedSegNet outperforms several advanced competing methods, yielding superior results. Additionally, the code can be accessed at https://github.com/csust-yixin/ConvMedSegNet.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

[Retracted] Long non­coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR­454/USP47 axis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 4C and 6D and the Transwell migration and invasion assay data shown in Figs. 4D, 6E and 6F were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time. Owing to the fact that contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 54, 2021; DOI: 10.3892/ijmm.2021.4887].

Novel miniature transendoscopic telerobotic system for endoscopic submucosal dissection (with videos).

BACKGROUND AND AIMS: The lack of tissue traction and instrument dexterity to allow for adequate visualization and effective dissection were the main issues in performing endoscopic submucosal dissection (ESD). Robot-assisted systems may provide advantages. In this study we developed a novel transendoscopic telerobotic system and evaluated its performance in ESD. METHODS: A miniature dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) was developed. The DREAMS system contained the current smallest robotic ESD instruments and was compatible with the commercially available dual-channel endoscope. After the system was established, a prospective randomized controlled study was conducted to validate the performance of the DREAMS-assisted ESD in terms of efficacy, safety, and workload by comparing it with the conventional technique. RESULTS: Two robotic instruments can achieve safe collaboration and provide sufficient visualization and efficient dissection during ESD. Forty ESDs in the stomach and esophagus of 8 pigs were completed by DREAMS-assisted ESD or conventional ESD. Submucosal dissection time was comparable between the 2 techniques, but DREAMS-assisted ESD demonstrated a significantly lower muscular injury rate (15% vs 50%, P = .018) and workload scores (22.30 vs 32.45, P < .001). In the subgroup analysis of esophageal ESD, DREAMS-assisted ESD showed significantly improved submucosal dissection time (6.45 vs 16.37 minutes, P = .002), muscular injury rate (25% vs 87.5%, P = .041), and workload (21.13 vs 40.63, P = .001). CONCLUSIONS: We developed a novel transendoscopic telerobotic system, named DREAMS. The safety profile and technical feasibility of ESD were significantly improved with the assistance of the DREAMS system, especially in the narrower esophageal lumen.

Manure application maintained the CO2 fixation activity of soil autotrophic bacteria but changed its ecological characteristics in an entisol of China.

The response of soil autotrophs to anthropogenic activities has attracted increasing attention against the background of global change. Here, three entisol plots under different fertilizing regimes, including no fertilization (CK), manure (M), and a combined application of chemical fertilizer and manure (NPKM) were selected, and then the soil RubisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) activity and cbbl (gene encoding the large subunit of RubisCO) composition were measured to indicate the activity and community of autotrophic bacteria, respectively. The results revealed that the RubisCO activity of CK showed no difference from that of M but was significantly higher than that of NPKM. The CK and M had the lowest and highest soil cbbl abundance, respectively. The α-diversity of soil cbbl-carrying bacteria showed no significant difference among these treatments, whereas they showed significantly different community structures of cbbl-carrying bacteria. Meanwhile, compared with CK, M had significantly lower abundances of bacterial species with the functions of nitrogen fixation (Azoarcus sp.KH32C) or detoxification (Methylibium petroleiphilum), indicating that manure application might have an inhibiting potential to some beneficial autotrophic bacterial species in this entisol.

Association between gaming disorder and regional homogeneity in highly involved male adult gamers: A pilot resting-state fMRI study.

BACKGROUND: Gaming behavior can induce cerebral changes that may be related to the neurobiological features of gaming disorder (GD). Additionally, individuals with higher levels of depression or impulsivity are more likely to experience GD. Therefore, the present pilot study explored potential neurobiological correlates of GD in the context of depression and impulsivity, after accounting for video gaming behavior. METHODS: Using resting-state functional magnetic resonance imaging (fMRI), a cross-sectional study was conducted with 35 highly involved male adult gamers to examine potential associations between GD severity and regional homogeneity (ReHo) in the entire brain. A mediation model was used to test the role of ReHo in the possible links between depression/impulsivity and GD severity. RESULTS: Individuals with greater GD severity showed increased ReHo in the right Heschl's gyrus and decreased ReHo in the right hippocampus (rHip). Furthermore, depression and impulsivity were negatively correlated with ReHo in the rHip, respectively. More importantly, ReHo in the rHip was found to mediate the associations between depression/impulsivity and GD. CONCLUSIONS: These preliminary findings suggest that GD severity is related to ReHo in brain regions associated with learning/memory/mood and auditory function. Higher levels of depression or impulsivity may potentiate GD through the functional activity of the hippocampus. Our findings advance our understanding of the neurobiological differences behind GD symptoms in highly involved gamers.

Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-Seq and Bulk RNA-Seq Analysis in GC.

BACKGROUND: Cellular senescence (CS) is thought to be the primary cause of cancer development and progression. This study aimed to investigate the prognostic role and molecular subtypes of CS-associated genes in gastric cancer (GC). METHODS: The CellAge database was utilized to acquire CS-related genes. Expression data and clinical information of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Patients were then grouped into distinct subtypes using the "ConsesusClusterPlus" R package based on CS-related genes. An in-depth analysis was conducted to assess the gene expression, molecular function, prognosis, gene mutation, immune infiltration, and drug resistance of each subtype. In addition, a CS-associated risk model was developed based on Cox regression analysis. The nomogram, constructed on the basis of the risk score and clinical factors, was formulated to improve the clinical application of GC patients. Finally, several candidate drugs were screened based on the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset. RESULTS: According to the cluster result, patients were categorized into two molecular subtypes (C1 and C2). The two subtypes revealed distinct expression levels, overall survival (OS) and clinical presentations, mutation profiles, tumor microenvironment (TME), and drug resistance. A risk model was developed by selecting eight genes from the differential expression genes (DEGs) between two molecular subtypes. Patients with GC were categorized into two risk groups, with the high-risk group exhibiting a poor prognosis, a higher TME level, and increased expression of immune checkpoints. Function enrichment results suggested that genes were enriched in DNA repaired pathway in the low-risk group. Moreover, the Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that immunotherapy is likely to be more beneficial for patients in the low-risk group. Drug analysis results revealed that several drugs, including ML210, ML162, dasatinib, idronoxil, and temsirolimus, may contribute to the treatment of GC patients in the high-risk group. Moreover, the risk model genes presented a distinct expression in single-cell levels in the GSE150290 dataset. CONCLUSION: The two molecular subtypes, with their own individual OS rate, expression patterns, and immune infiltration, lay the foundation for further exploration into the GC molecular mechanism. The eight gene signatures could effectively predict the GC prognosis and can serve as reliable markers for GC patients.

4D Additive-Subtractive Manufacturing of Shape Memory Ceramics.

The development of high-temperature structural materials, such as ceramics, is limited by their extremely high melting points and the difficulty in building complicated architectures. Four-dimensional (4D) printing helps enhance the geometrical flexibility of ceramics. However, ceramic 4D printing systems are limited by the separate processes for shape and material transformations, low accuracy of morphing systems, low resolution of ceramic structures, and their time-intensive nature. Here, a paradigm for a one-step shape/material transformation, high-2D/3D/4D-precision, high-efficiency, and scalable 4D additive-subtractive manufacturing of shape memory ceramics is developed. Original/reverse and global/local multimode shape memory capabilities are achieved using macroscale SiOC-based ceramic materials. The uniformly deposited Al2 O3 -rich layer on the printed SiOC-based ceramic lattice structures results in an unusually high flame ablation performance of the complex-shaped ceramics. The proposed framework is expected to broaden the applications of high-temperature structural materials in the aerospace, electronics, biomedical, and art fields.

Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a widely used standard therapy for critically ill patients with acute kidney injury (AKI). Despite its effectiveness, treatment is often interrupted due to clot formation in the extracorporeal circuits. Anticoagulation is a crucial strategy for preventing extracorporeal circuit clotting during CRRT. While various anticoagulation options are available, there were still no studies synthetically comparing the efficacy and safety of these anticoagulation options. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to October 31, 2022. All randomized controlled trials (RCTs) that examined the following outcomes were included: filter lifespan, all-cause mortality, length of stay, duration of CRRT, recovery of kidney function, adverse events and costs. RESULTS: Thirty-seven RCTs from 38 articles, comprising 2648 participants with 14 comparisons, were included in this network meta-analysis (NMA). Unfractionated heparin (UFH) and regional citrate anticoagulation (RCA) are the most frequently used anticoagulants. Compared to UFH, RCA was found to be more effective in prolonging filter lifespan (MD 12.0, 95% CI 3.8 to 20.2) and reducing the risk of bleeding. Regional-UFH plus Prostaglandin I2 (Regional-UFH + PGI2) appeared to outperform RCA (MD 37.0, 95% CI 12.0 to 62.0), LMWH (MD 41.3, 95% CI 15.6 to 67.0), and other evaluated anticoagulation options in prolonging filter lifespan. However, only a single included RCT with 46 participants had evaluated Regional-UFH + PGI2. No statistically significant difference was observed in terms of length of ICU stay, all-cause mortality, duration of CRRT, recovery of kidney function, and adverse events among most evaluated anticoagulation options. CONCLUSIONS: Compared to UFH, RCA is the preferred anticoagulant for critically ill patients requiring CRRT. The SUCRA analysis and forest plot of Regional-UFH + PGI2 are limited, as only a single study was included. Additional high-quality studies are necessary before any recommendation of Regional-UFH + PGI2. Further larger high-quality RCTs are desirable to strengthen the evidence on the best choice of anticoagulation options to reduce all-cause mortality and adverse events and promote the recovery of kidney function. Trial registration The protocol of this network meta-analysis was registered on PROSPERO ( CRD42022360263 ). Registered 26 September 2022.

Estimation of the cumulative risks from dietary exposure to cadmium, arsenic, nickel, lead and chromium in Guangzhou, China.

Heavy metals, such as cadmium and lead, are ubiquitously present as single substances and compounds in the environment. These substances have various and overlapping health effects. Consumption of contaminated foods is the main pathway of the human exposure, however, estimation of their dietary exposure in combination with health risk analysis, particularly at various endpoints, has rarely been reported. In this study, we integrated relative potency factor (RPF) analysis into the margin of exposure (MOE) model to evaluate the health risk of combined heavy metal (including cadmium, arsenic, lead, chromium, and nickel) exposure in the residents in Guangzhou, China, after quantifying the heavy metals in various food samples and estimating their dietary exposure. The results indicated that rice, rice products and leafy vegetables contributed primarily to the dietary exposure of all metals except arsenic, which exposed the population largely through consumption of sea-foods. With all the five metals contributing to nephro- and neurotoxicity, the 95% confidence limits of MOE for the residents were clearly below 1.0 in the 3∼6-year group, suggesting a recognizable risk to young children. This study provides substantial evidence for the non-negligible health risk in young children due to increased heavy metal exposure,at least on some toxicity targets.

[Determination of 39 fatty acids in liver of rats by gas chromatography-mass spectrometry].

Fatty acids not only form phospholipids that contribute to the formation of cell membranes but also participate in many metabolic activities, such as energy storage and cell signal transduction. The liver plays a key role in the synthesis and metabolism of fatty acids. The composition and contents of fatty acids in the liver are closely related to body health. Most fatty acid-detection methods require a large sample size and can detect only a small number of fatty acids. Therefore, a sensitive and efficient method to determine fatty acids in the liver is urgently required. Herein, a method based on gas chromatography-mass spectrometry (GC-MS) was established for the simultaneous determination of 39 fatty acids in 1.1 mg of liver tissue. Different extraction methods and derivatization conditions were compared to develop an optimal sample-treatment method. The performance of two different columns in separating the target fatty acids were also compared. A total of 10 mg of liver was added to 450 µL of normal saline and ground at -35 ℃ to obtain a homogenate. Next, 50 µL of the homogenate (equivalent to 1.1 mg of liver) was added with 750 µL of chloroform-methanol (1∶2, v/v) to extract total fatty acids. The fatty acid extracts were dried under nitrogen, and then derivatized at 100 ℃ for 90 min after being added with methanol containing 5% sulfuric acid. The fatty acid methyl esters were extracted with hexane and then separated on an SP-2560 capillary column (100 m×0.25 mm×0.2 µm; Supelco, USA) via GC-MS. The results revealed that all 39 fatty acid methyl esters detected had good linearities in the certain mass concentration ranges with correlation coefficients (R2) greater than 0.9940. The limits of detection (LOD) and quantification (LOQ) of these methyl esters in the liver were 2-272 ng/mg and 7-906 ng/mg, respectively. The accuracy and precision of the method were evaluated by spiking the liver homogenate with tridecylic acid and eicosanoic acid at low (0.09 µg/mg), moderate (0.90 µg/mg), and high (5.40 µg/mg) concentration levels. The recoveries ranged from 82.4% to 101.0% with an intraday relative standard deviations (RSDs) (n=5) of 3.2%-12.0% and interday RSDs (n=3) of 5.4%-13.4%. The method was successfully applied to detect fatty acids in the livers of four healthy male Sprague-Dawley (SD) rats and four male SD rats with abnormal liver function induced by perfluorooctane sulfonate (PFOS). PFOS is a persistent organic pollutant. Twenty-six fatty acids were detected in the livers of both groups. Among the fatty acids investigated, pentadecanoic acid (C15∶0), γ-linolenic acid (C18∶3n6), and elaidic acid (C18∶1n9t) cannot be detected by the methods reported in the literature. By contrast, the method developed in this study could separate the isomers of oleic acid (elaidic acid, C18∶1n9t; oleic acid, C18∶1n9c) and linolenic acid (linolelaidic acid, C18∶2n6t; linoleic acid, C18∶2n6c). In conclusion, the developed method is simple and can detect a large number of fatty acids using small sample amounts and few reagents. More importantly, it could successfully separate fatty acid isomers. These findings indicate that the developed method is suitable for the detection of fatty acid composition and contents in the liver in clinical and experimental research.

Extracorporeal carbon dioxide removal for patients with acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory failure (ARF) is a common clinical critical syndrome with substantial mortality. Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for the treatment of ARF. However, whether ECCO2R could provide a survival advantage for patients with ARF is still controversial. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) and observational studies that examined the following outcomes were included: mortality, length of hospital and ICU stay, intubation and tracheotomy rate, mechanical ventilation days, ventilator-free days (VFDs), respiratory parameters, and reported adverse events. RESULTS: Four RCTs and five observational studies including 1173 participants with ARF due to COPD or ARDS were included in this meta-analysis. Pooled analyses of related studies showed no significant difference in overall mortality between ECCO2R and control group, neither in RCTs targeted ARDS or acute hypoxic respiratory failure patients (RR 1.05, 95% CI 0.83 to 1.32, p = 0.70, I2 =0.0%), nor in studies targeted patients with ARF secondary to COPD (RR 0.80, 95% CI 0.58 to 1.11, p = 0.19, I2 =0.0%). A shorter duration of ICU stay in the ECCO2R group was only obtained in observational studies (WMD -4.25, p < 0.01), and ECCO2R was associated with a longer length of hospital stay (p = 0.02). ECCO2R was associated with lower intubation rate (p < 0.01) and tracheotomy rate (p = 0.01), and shorter mechanical ventilation days (p < 0.01) in comparison to control group in ARF patients with COPD. In addition, an improvement in pH (p = 0.01), PaO2 (p = 0.01), respiratory rate (p < 0.01), and PaCO2 (p = 0.04) was also observed in patients with COPD exacerbations by ECCO2R therapy. However, the ECCO2R-related complication rate was high in six of the included studies. CONCLUSIONS: Our findings from both RCTs and observational studies did not confirm a significant beneficial effect of ECCO2R therapy on mortality. A shorter length of ICU stay in the ECCO2R group was only obtained in observational studies, and ECCO2R was associated with a longer length of hospital stay. ECCO2R was associated with lower intubation rate and tracheotomy rate, and shorter mechanical ventilation days in ARF patients with COPD. And an improvement in pH, PaO2, respiratory rate and PaCO2 was observed in the ECCO2R group. However, outcomes largely relied on data from observational studies targeted patients with ARF secondary to COPD, thus further larger high-quality RCTs are desirable to strengthen the evidence on the efficacy and benefits of ECCO2R for patients with ARF.Key messagesECCO2R therapy did not confirm a significant beneficial effect on mortality.ECCO2R was associated with lower intubation and tracheotomy rate, and shorter mechanical ventilation days in patients with ARF secondary to COPD.An improvement in pH, PaO2, respiratory rate, and PaCO2 was observed in ECCO2R group in patients with COPD exacerbations.Evidence for the future application of ECCO2R therapy for patients with ARF. The protocol of this meta-analysis was registered on PROSPERO (CRD42022295174).

High cut-off membranes in patients requiring renal replacement therapy: a systematic review and meta-analysis.

BACKGROUND: Whether high cut-off (HCO) membranes are more effective than high-flux (HF) membranes in patients requiring renal replacement therapy (RRT) remains controversial. The aim of this systematic review was to investigate the efficacy of HCO membranes regarding the clearance of inflammation-related mediators, ß2-microglobulin and urea; albumin loss; and all-cause mortality in patients requiring RRT. METHODS: We searched all relevant studies on PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure, with no language or publication year restrictions. Two reviewers independently selected studies and extracted data using a prespecified extraction instrument. Only randomized controlled trials (RCTs) were included. Summary estimates of standardized mean differences (SMDs) or weighted mean differences (WMDs) and risk ratios (RRs) were obtained by fixed-effects or random-effects models. Sensitivity analyses and subgroup analyses were performed to determine the source of heterogeneity. RESULTS: Nineteen RCTs involving 710 participants were included in this systematic review. Compared with HF membranes, HCO membranes were more effective in reducing the plasma level of interleukin-6 (IL-6) (SMD -0.25, 95% confidence interval (CI) -0.48 to -0.01, P   =  0.04, I2  = 63.8%); however, no difference was observed in the clearance of tumor necrosis factor-α (TNF-α) (SMD 0.03, 95% CI -0.27 to 0.33, P  = 0.84, I2  = 4.3%), IL-10 (SMD 0.22, 95% CI -0.12 to 0.55, P  = 0.21, I2  = 0.0%), or urea (WMD -0.27, 95% CI -2.77 to 2.23, P  = 0.83, I2  = 19.6%). In addition, a more significant reduction ratio of ß 2 -microglobulin (WMD 14.8, 95% CI 3.78 to 25.82, P  = 0.01, I2  = 88.3%) and a more obvious loss of albumin (WMD -0.25, 95% CI -0.35 to -0.16, P  < 0.01, I2  = 40.8%) could be observed with the treatment of HCO membranes. For all-cause mortality, there was no difference between the two groups (risk ratio [RR] 1.10, 95% CI 0.87 to 1.40, P  = 0.43, I2  = 0.0%). CONCLUSIONS: Compared with HF membranes, HCO membranes might have additional benefits on the clearance of IL-6 and ß 2-microglobulin but not on TNF-α, IL-10, and urea. Albumin loss is more serious with the treatment of HCO membranes. There was no difference in all-cause mortality between HCO and HF membranes. Further larger high-quality RCTs are needed to strengthen the effects of HCO membranes.

Altered HLA-A2-restricted TP53 epitope induces specific CTL cytotoxicity against hepatocellular carcinoma.

High-frequency mutation of the TP53 tumor suppressor gene is observed in multiple human cancers, which promotes cancer progression. However, the mutated gene-encoded protein may serve as a tumor antigen to elicit tumor-specific immune responses. In this study, we detected widespread expression of shared TP53-Y220C neoantigen in hepatocellular carcinoma with low affinity and low stability of binding to HLA-A0201 molecules. We substituted the amino acid sequences VVPCEPPEV with VLPCEPPEV in the TP53-Y220C neoantigen to yield a TP53-Y220C (L2) neoantigen. This altered neoantigen was found to increase affinity and stability and induce more cytotoxic T lymphocytes (CTLs), indicating improvements in immunogenicity. In vitro assays showed the cytotoxicity of CTLs stimulated by both TP53-Y220C and TP53-Y220C (L2) neoantigens against multiple HLA-A0201-positive cancer cells expressing TP53-Y220C neoantigens; however, the TP53-Y220C (L2) neoantigen showed higher cytotoxicity than the TP53-Y220C neoantigen against cancer cells. More importantly, in vivo assays demonstrated greater inhibition of hepatocellular carcinoma cell proliferation by TP53-Y220C (L2) neoantigen-specific CTLs relative to TP53-Y220C neoantigen in zebrafish and nonobese diabetic/severe combined immune deficiency mouse models. The results of this study demonstrate enhanced immunogenicity of the shared TP53-Y220C (L2) neoantigen, which has the potential as dendritic cells or peptide vaccines for multiple cancers.

A new class of nucleating agents for poly(L-lactic acid): Environmentally-friendly metal salts with biomass-derived ligands and advanced nucleation ability.

Adding nucleating agents has been a successful strategy to boost the heat resistance of poly(L-lactic acid) (PLLA) by increasing the crystallinity. In this study, a new series of bio-based complexes as nucleating agents for PLLA, including twelve combinations of three eco-friendly metal ions (Zn, Mg, Ca) and four biomass-derived α-hydroxy acids, were successfully synthesized to respectively investigate the effects of metal ions as well as ligands on nucleation capacity of complexes. By investigating the non-isothermal and isothermal crystallization at 135 °C of PLLA with 0.3 wt% loading of complexes, both zinc and magnesium salts of L-mandelic acid showed excellent nucleation capacities. And magnesium L-mandelate performed better, raising the crystallinity of PLLA to 44.4 % as well as minimizing its crystallization half-time from 73 min to 2.7 min. The growth and denser distribution of PLLA spherulites on the salt surface were also observed by POM, reflecting epitaxial nucleation as the possible mechanism. A novel inspiration, utilizing VESTA software to simulate the crystal structure of zinc L-mandelate (Zn(L-MA)2), was proposed to determine the nucleation mechanism. Also, using polyethylene terephthalate (PET) as a test protocol, the rationality of the model could be approved by checking the fitness of nucleating prediction and experiment results.

Phospholipase A2 induces acute kidney injury by complement mediated mitochondrial apoptosis via TNF-α/NF-κB signaling pathway.

OBJECTIVE: Acute kidney injury (AKI) is one of common complications of wasp/bee stings. Phospholipase A2 (PLA2) is a vital pathogenic composition of wasp/bee venom. We aimed to investigate the role of complement mediated mitochondrial apoptosis in PLA2 induced AKI. MATERIALS AND METHODS: PLA2 induced AKI model was established by injecting PLA2 into via tail vein on mice. The pathological changes and the microstructural changes of kidney, complement activation, inflammation and apoptosis were detected in vitro and in vivo respectively. RESULTS: The results showed that PLA2 induced AKI models were successfully established in vivo and vitro. Compared with control, serum creatinine and urea nitrogen levels were elevated. Complement system activation and mitochondrial damage were observed. Expressions of IL-6, TNF-α, cleaved caspase-3 and cleaved caspase-9, and Bax/Bcl-2 increased in PLA2 induced AKI models. TNF-α/NF-κB signaling pathway activation in AKI models. CONCLUSION: In the present study, PLA2 induced AKI model was first successfully established to our knowledge. The role of complement mediated mitochondrial apoptosis pathway in renal tubular epithelial cells in PLA2 induced AKI were verified in vitro and vivo.

Cloning, distribution, and effects of growth regulation of MC3R and MC4R in red crucian carp (Carassius auratus red var.).

Background: Melanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of mc3r and mc4r in the energy homeostasis of red crucian carp (Carassius auratus red var., RCC), we cloned mc3r and mc4r, analyzed the tissue expression and localization of the genes, and investigated the effects of knockout of mc3r (mc3r +/-) and mc4r (mc4r +/-) in RCC. Results: The full-length cDNAs of RCC mc3r and mc4r were 1459 base pairs (bp) and 1894 bp, respectively. qRT-PCR indicated that mc3r and mc4r were profusely expressed in the brain, but lower expressed in the periphery tissues. ISH revealed that mc3r and mc4r were located in NPP, NPO, NAPv, NSC, NAT, NRL, NLTl, and NLTp of the brain, suggesting that mc3r and mc4r might regulate many physiological and behavioral aspects in RCC. To further verify the roles of mc3r and mc4r in energy homeostasis, the mc3r+/- and mc4r+/- fish were obtained by the CRISPR/Cas9 system. The average body weights, total lengths, body depths, and food intake of mc4r+/- fish were significantly higher than those of mc3r+/- and the normal wild-type (WT) fish, but there was no difference between the mc3r+/- and WT fish, indicating that the RCC phenotype and food intake were mainly influenced by mc4r but not mc3r. Interestingly, mc4r+/- fish displayed more visceral fat mass than mc3r+/- and WT fish, and mc3r+/- fish also exhibited slightly more visceral fat mass compared to WT. RNA-seq of the liver and muscle revealed that a large number of differentially expressed genes (DEGs) differed in WT vs. mc3r+/-, WT vs. mc4r+/-, and mc3r+/- vs. mc4r+/-, mainly related to lipid, glucose, and energy metabolism. The KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways such as steroid biosynthesis, fatty acid metabolism, fatty acid biosynthesis, glycolysis/gluconeogenesis, wnt signaling pathway, PPAR signaling pathway, and MAPK signaling pathway, thereby affecting lipid accumulation and growth. Conclusion: In conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish.

Altered MUC1 epitope-specific CTLs: A potential target for immunotherapy of pancreatic cancer.

The efficacy of conventional treatments for pancreatic cancer remains unsatisfactory, and immunotherapy is an emerging option for adjuvant treatment of this highly deadly disorder. The tumor-associated antigen (TAA) MUC1 is expressed in a variety of human cancers and is overexpressed in more than 90% of pancreatic cancer, which makes it an attractive target for cancer immunotherapy. As a self-protein, MUC1 shows a low immunogenicity because of immune tolerance, and the most effective approach to breaking immune tolerance is alteration of the antigen structure. In this study, the altered MUC11068-1076Y1 epitope (YLQRDISEM) by modification of amino acid residues in sequences presented a higher immunogenicity and elicited more CTLs relative to the wild-type (WT) MUC11068-1076 epitope (ELQRDISEM). In addition, the altered MUC11068-1076Y1 epitope was found to cross-recognize pancreatic cancer cells expressing WT MUC1 peptides in an HLA-A0201-restricted manner and trigger stronger immune responses against pancreatic cancer via the perforin/granzyme apoptosis pathway. As a potential HLA-A0201-restricted CTL epitope, the altered MUC11068-1076Y1 epitope is considered as a promising target for immunotherapy of pancreatic cancer. Alteration of epitope residues may be feasible to solve the problem of the low immunogenicity of TAA and break immune tolerance to induce immune responses against human cancers.

Genetic and genomic signatures in ethanol withdrawal seizure-prone and seizure-resistant mice implicate genes involved in epilepsy and neuronal excitability.

Alcohol withdrawal is a clinically important consequence and potential driver of Alcohol Use Disorder. However, susceptibility to withdrawal symptoms, ranging from craving and anxiety to seizures and delirium, varies greatly. Selectively bred Withdrawal Seizure-Prone (WSP) and Seizure-Resistant (WSR) mice are an animal model of differential susceptibility to withdrawal and phenotypes with which withdrawal severity correlates. To identify innate drivers of alcohol withdrawal severity, we performed a multi-omic study of the WSP and WSR lines and F2 mice derived from them, using genomic, genetic, and transcriptomic analyses. Genes implicated in seizures and epilepsy were over-represented among those that segregated between WSP and WSR mice and that displayed differential expression in F2 mice high and low in withdrawal. Quantitative trait locus (QTL) analysis of ethanol withdrawal convulsions identified several genome-wide significant loci and pointed to genes that modulate potassium channel function and neural excitability. Perturbations of expression of genes involved in synaptic transmission, including GABAergic and glutamatergic genes, were prominent in prefrontal cortex transcriptome. Expression QTL (eQTL) analysis fine mapped genes within the peak ethanol withdrawal QTL regions. Genetic association analysis in human subjects provided converging evidence for the involvement of those genes in severity of alcohol withdrawal and dependence. Our results reveal a polygenic network and neural signaling pathways contributing to ethanol withdrawal seizures and related phenotypes that overlap with genes modulating epilepsy and neuronal excitability.

Imaging characteristics of ovarian sclerosing stromal tumor.

OBJECTIVES: This study was designed to evaluate the specific imaging features of ovarian sclerosing stromal tumor (SST), improve its accuracy as well as the specificity of imaging diagnosing, and prevent overestimation of malignancy to reduce unnecessary surgical procedures. METHODS: Eight patients with magnetic resonance imaging (MRI) and six with computed tomography (CT) images were analyzed in this retrospective observational study. All the cases were confirmed by postoperative pathological examination as those of ovarian SST. Imaging and pathological features were also evaluated. RESULTS: All the 14 masses displayed cystic and solid components with outer surface of tumors contained a capsular and complete smooth rim. Eight tumors of MRI exhibited "lake-island" sign on T2 weighted imaging (T2WI). Two of the 6 CT cases displayed a flaky calcification. One case showed as a multiloculated cystic mass with irregularly thickened septae and the tumor wall. The solid components in other 13 masses were comb- or wheel-like enhanced. After injection of contrast agent, the solid components in 8 cases (57.1%) appeared as early enhancement, whereas the other 6 cases (42.9%) appeared as progressive enhanced, and the cystic components of all the cases had no enhancement in the whole course. Vascular flow signals or/and marked enhancement of the blood vessels were found in 12 lesions (85.7%). Pathological examination demonstrated pseudolobule patterns, round to spindle shaped cells, collagenous areas, edematous hypocellular areas and prominent vasculatures. CONCLUSIONS: The results demonstrated that MRI with "lake-island" signs on T2WI and MRI/CT dynamic enhancement could potentially play a critical role in facilitating appropriate diagnosis preoperatively.