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Abstract Over the past decade, the role of the 14–3-3 protein has received increasing interest. Seven subtypes of 14–3-3 proteins exhibit high homology; however, each subtype maintains its specificity. The 14–3-3ε protein is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cell cycle regulation, repolarization of cardiac action, cardiac development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant role in the development and progression of various diseases, such as cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancer. These immense and various involvements of 14–3-3ε in diverse processes makes it a promising target for drug development. Although extensive research has been conducted on 14–3-3 dimers, studies on 14–3-3 monomers are limited. This review aimed to provide an overview of recent reports on the molecular mechanisms involved in the regulation of binding partners by 14–3-3ε, focusing on issues that could help advance the frontiers of this field. Video Abstract

Abstract Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.

This study aimed to evaluate the disruption of the swine gut microbiota and histopathological changes caused by infection with enterotoxigenic E. coli. Fecal samples were collected from piglets suffering from diarrhea post-recovery and healthy animals. Intestinal tissues were collected for histopathological changes. The results revealed histopathological changes mainly in the ileum of the infected animals compared to those in the ileum of the control and recovered animals. The operational taxonomic units (OTUs) revealed that the E. coli diarrheal group exhibited the highest bacterial richness. Principal coordinate analysis (PCoA) corroborated the presence of dysbiosis in the gut microbiota following E. coli-induced diarrhea. While the normal control and infected groups displayed slight clustering, the recovery group formed a distinct cluster with a distinct flora. Bacteroidetes, Firmicutes, and Fusobacteria were the dominant phyla in both the healthy and recovered piglets and in the diarrheal group. LEfSe and the associated LDA score analysis revealed that the recovered group exhibited dominance of the phyla Euryarchaeota and Bacteroidota, while groups N and I showed dominance of the phyla Firmicutes and Fusobacteriota, respectively. The LDA scores highlighted a significant expression of the Muribaculacea family in group R. The obtained findings will help in understanding the microbiome during swine colibacillosis, which will support control of the outbreaks.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

This study evaluated the anti-inflammation effect of the three main short-chain fatty acids (SCFAs) on Acinetobacter baumannii-induced THP-1 cells. The three main SCFAs could inhibit A. baumannii-stimulated THP-1 cell NF-κB pathway activity and the expressions of NLRP3 inflamma-some and GSDMD, and increase autophagy. The three main SCFAs, especially the sodium butyrate (NaB), had the effect of down-regulation of ROS and TLR-2 expression in THP-1 cells. NaB and sodium propionate (NaPc), but not sodium acetate (NaAc), dramatically suppressed IL-1β and IFN-γ expression. The results indicated that NaB and NaPc could significantly inhibit the inflammation of THP-1 cells induced by A. baumannii, and the inhibitory effect was in the order of NaB > NaPc > NaAC. NaB and NaPc may inhibit inflammation through TLR-2/NF-κB/ROS/NLRP3 signaling pathway.

Abstract Chondrogenesis is the formation of chondrocytes and cartilage tissues and starts with mesenchymal stem cell (MSC) recruitment and migration, condensation of progenitors, chondrocyte differentiation, and maturation. The chondrogenic differentiation of MSCs depends on co-regulation of many exogenous and endogenous factors including specific microenvironmental signals, non-coding RNAs, physical factors existed in culture condition, etc. Cancer stem cells (CSCs) exhibit self-renewal capacity, pluripotency and cellular plasticity, which have the potential to differentiate into post-mitotic and benign cells. Accumulating evidence has shown that CSCs can be induced to differentiate into various benign cells including adipocytes, fibrocytes, osteoblast, and so on. Retinoic acid has been widely used in the treatment of acute promyelocytic leukemia. Previous study confirmed that polyploid giant cancer cells, a type of cancer stem-like cells, could differentiate into adipocytes, osteocytes, and chondrocytes. In this review, we will summarize signaling pathways and cytokines in chondrogenic differentiation of MSCs. Understanding the molecular mechanism of chondrogenic differentiation of CSCs and cancer cells may provide new strategies for cancer treatment.

Nephropathy injury is a prevalent complication observed in individuals with diabetes, serving as a prominent contributor to end-stage renal disease, and the advanced glycation products (AGEs) are important factors that induce kidney injury in patients with diabetes. Addressing this condition remains a challenging aspect in clinical practice. The aim of this study was to explore the effects of Lactiplantibacillus plantarum NKK20 strain (NKK20) which protects against diabetic kidney disease (DKD) based on animal and cell models. The results showed that the NKK20 can significantly reduce renal inflammatory response, serum oxidative stress response, and AGE concentration in diabetic mice. After treatment with NKK20, the kidney damage of diabetic mice was significantly improved, and more importantly, the concentration of butyrate, a specific anti-inflammatory metabolite of intestinal flora in the stool of diabetic mice, was significantly increased. In addition, nontargeted metabolomics analysis showed a significant difference between the metabolites in the mouse serum contents of the NKK20 administration group and those in the nephropathy injury group, in which a total of 24 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in glycerophospholipid metabolism and arachidonic acid metabolism. Also, the administration of butyrate to human kidney- (HK-) 2 cells that were stimulated by AGEs resulted in a significant upregulation of ZO-1, Occludin, and E-cadherin gene expressions and downregulation of α-SMA gene expression. This means that butyrate can maintain the tight junction structure of HK-2 cells and inhibit fibrosis. Butyrate also significantly inhibited the activation of PI3K/Akt pathway. These results indicate that NKK20 can treat kidney injury in diabetic mice by reducing blood glucose and AGE concentration and increasing butyrate production in the intestine. By inhibiting PI3K pathway activation in HK-2 cells, butyrate maintains a tight junction structure of renal tubule epithelial cells and inhibits renal tissue fibrosis. These results suggest that NKK20 is helpful to prevent and treat the occurrence and aggravation of diabetic kidney injury.

Metastasis, a primary cause of death in patients with malignancies, is promoted by intrinsic changes in both tumor and non-malignant cells in the tumor microenvironment (TME). As major components of the TME, tumor-associated neutrophils (TANs) promote tumor progression and metastasis through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together establish an immunosuppressive TME. In this review, we describe the potential mechanisms by which TANs participate in tumor metastasis based on recent experimental evidence. We have focused on drugs in chemotherapeutic regimens that target TANs, thereby providing a promising future for cancer immunotherapy.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.

Liquid–liquid phase separation may be a mechanism for organizing the presynaptic nerve terminal. Here, the authors show that PKC-mediated phosphorylation of Liprin-α3 triggers phase separation in cell lines and modulates active zone structure and function in primary hippocampal neurons.

This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1β and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.

Cell fusion is involved in many physiological and pathological processes, including gamete binding, and cancer development. The basic processes of cell fusion include membrane fusion, cytoplasmic mixing, and nuclear fusion. Cell fusion is regulated by different proteins and signaling pathways. Syncytin-1, syncytin-2, glial cell missing 1, galectin-1 and other proteins (annexins, myomaker, myomerger etc.) involved in cell fusion via the cyclic adenosine-dependent protein kinase A, mitogen-activated protein kinase, wingless/integrase-1, and c-Jun N-terminal kinase signaling pathways. In the progression of malignant tumors, cell fusion is essential during the organ-specific metastasis, epithelial-mesenchymal transformation, the formation of cancer stem cells (CSCs), cancer angiogenesis and cancer immunity. In addition, diploid cells can be induced to form polyploid giant cancer cells (PGCCs) via cell fusion under many kinds of stimuli, including cobalt chloride, chemotherapy, radiotherapy, and traditional Chinese medicine. PGCCs have CSC-like properties, and the daughter cells derived from PGCCs have a mesenchymal phenotype and exhibit strong migration, invasion, and proliferation abilities. Therefore, exploring the molecular mechanisms of cell fusion can enable us better understand the development of malignant tumors. In this review, the basic process of cell fusion and its significance in cancer is discussed.

Abstract Background Human papillomavirus (HPV) testing has been employed by several European countries to augment cytology-based cervical screening programs. A number of research groups have demonstrated potential utility of next-generation sequencing (NGS) for HPV genotyping, with comparable performance and broader detection spectrum than current gold standards. Nevertheless, most of these NGS platforms may not be the best choice for medium sample throughput and laboratories with less resources and space. In light of this, we developed a Nanopore sequencing assay for HPV genotyping and compared its performance with cobas HPV Test and Roche Linear Array HPV Genotyping Test (LA). Methods Two hundred and one cervicovaginal swabs were routinely tested for Papanicolaou smear, cobas HPV Test and LA. Residual DNA was used for Nanopore protocol after routine testing. Briefly, HPV L1 region was amplified using PGMY and MGP primers, and PCR-positive specimens were sequenced on MinION flow cells (R9.4.1). Data generated in first 2 h were aligned with reference sequences from Papillomavirus Episteme database for genotyping. Results Nanopore detected 96 HPV-positive (47.76%) and 95 HPV-negative (47.26%) specimens, with 10 lacking β-globin band and not further analyzed (4.98%). Substantial agreement was achieved with cobas HPV Test and LA (κ: 0.83–0.93). In particular, Nanopore appeared to be more sensitive than cobas HPV Test for HPV 52 (n = 7). For LA, Nanopore revealed higher concordance for high-risk (κ: 0.93) than non-high risk types (κ: 0.83), and with similar high-risk positivity in each cytology grading. Nanopore also provided better resolution for HPV 52 in 3 specimens co-infected with HPV 33 or 58, and for HPV 87 which was identified as HPV 84 by LA. Interestingly, Nanopore identified 5 additional HPV types, with an unexpected high incidence of HPV 90 (n = 12) which was reported in North America and Belgium but not in Hong Kong. Conclusions We developed a Nanopore workflow for HPV genotyping which was economical (about USD 50.77 per patient specimen for 24-plex runs), and with comparable or better performance than 2 reference methods in the market. Future prospective study with larger sample size is warranted to further evaluate test performance and streamline the protocol.

Abstract Background Diversified etiology of lower respiratory tract infection renders diagnosis challenging. The mainstay microbial culture is time-consuming and constrained by variable growth requirements. In this study, we explored the use of Nanopore sequencing as a supplementary tool to alleviate this diagnostic bottleneck. Methods We developed a targeted Nanopore method based on amplification of bacterial 16S rRNA gene and fungal internal transcribed spacer region. The performance was compared with routine infectious disease workups on 43 respiratory specimens. Results Nanopore successfully identified majority of microbes (47/54, 87.04%) and 7 possible pathogens not detected by routine workups, which were attributable to the content of microbiological investigations (n = 5) and negative culture (n = 2). The average sequencing time for first target reads was 7 min (1–43 min) plus 5 h of pre-sequencing preparation. Conclusions The Nanopore method described here was rapid, economical and hypothesis-free, which might provide valuable hints to further microbiological follow-up for opportunistic pathogens missed or not detectable by conventional tests.

In recent years, sodium butyrate has gained increased attention for its numerous beneficial properties. However, whether sodium butyrate could alleviate inflammatory damage by macrophage activation and its underlying mechanism remains unclear. The present study used an advanced glycosylation products- (AGEs-) induced inflammatory damage model to study whether sodium butyrate could alleviate oxidative stress, inflammation, and metabolic dysfunction of human monocyte-macrophage originated THP-1 cells in a PI3K-dependent autophagy pathway. The results indicated that sodium butyrate alleviated the AGEs-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased malondialdehyde (MDA) and mRNA expression of pro-inflammatory cytokines of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and increased the content of superoxide dismutase (SOD). Sodium butyrate reduced the protein expression of the NLR family, pyrin domain-containing protein 3 (NLRP3) and Caspase-1, and decreased the nucleus expression of nuclear factor-kappaB (NF-κB). Sodium butyrate decreased the expression of light-chain-associated protein B (LC3B) and Beclin-1, and inhibited autophagy. Moreover, sodium butyrate inhibited the activation of the PI3K/Akt pathway in AGEs-induced THP-1 cells. In addition, the metabolomics analysis showed that sodium butyrate could affect the production of phosphatidylcholine, L-glutamic acid, UDP-N-acetylmuraminate, biotinyl-5’-AMP, and other metabolites. In summary, these results revealed that sodium butyrate inhibited autophagy and NLRP3 inflammasome activation by blocking the PI3K/Akt/NF-κB pathway, thereby alleviating oxidative stress, inflammation, and metabolic disorder induced by AGEs.

Short-chain fatty acids (SCFAs) are important anti-inflammatory metabolites of intestinal flora. Oxidized low-density lipoprotein (ox-LDL)-induced macrophage activation is critical for the formation of atherosclerosis plaque. However, the association between SCFAs and ox-LDL-induced macrophage activation with respect to the formation of atherosclerosis plaque has not yet been elucidated. The present study investigated whether SCFAs (sodium acetate, sodium propionate, and sodium butyrate) can affect ox-LDL-induced macrophage activation and potential signaling pathways via regulation of the expression of the NLRP3/Caspase-1 pathway. Using human monocyte-macrophage (THP-1) cells as a model system, it was observed that ox-LDL not only induced cell inflammatory injury but also activated the NLRP3/Caspase-1 pathway. The exogenous supplementation of three SCFAs could significantly inhibit cell inflammatory injury induced by ox-LDL. Moreover, three SCFAs decreased the expression of IL-1β and TNF-α via the inactivation of the NLRP3/Caspase-1 pathway induced by ox-LDL. Furthermore, three SCFAs affected cellular metabolism in ox-LDL-induced macrophages, as detected by untargeted metabolomics analysis. The results of the present study indicated that three SCFAs inhibited ox-LDL-induced cell inflammatory injury by blocking the NLRP3/Caspase-1 pathway, thereby improving cellular metabolism. These findings may provide novel insights into the role of SCFA intervention in the progression of atherosclerotic plaque formation.

Arsenic trioxide (ATO) has been used to treat acute promyelocytic leukemia. However, it is not effective in treating solid tumors such as colorectal cancer. We have previously reported that polyploid giant cancer cells (PGCCs) exhibiting the characteristics of cancer stem cells can be generated by various inducers. In this study, ATO was used to induce the formation of PGCCs in LoVo and Hct116 colon cancer cell lines. The migration, invasion, and proliferation abilities of colon cancer cells with and without ATO treatment were assessed by wound-healing, transwell, and plate colony formation assays. The expression of epithelial to mesenchymal transition-related proteins and erythroid differentiation-related proteins in colon cancer cells was further evaluated by western blot and immunocytochemical assays. LoVo and Hct116 cells were transfected with a eukaryotic expression vector for green fluorescent protein (GFP), red fluorescent protein (RFP), H2B-GFP, and H2B-mCherry to study PGCCs formation via cell fusion. WB and ICC assays were performed to assess the expression of cell fusion-related proteins. MG132, small interfering RNA-glial cell missing 1 (GCM1), and chromatin immunoprecipitation-polymerase chain reaction assays were performed to study the role of GCM1/syncytin-1-mediated cell fusion. Clinically, the significance of cell fusion-related proteins and erythroid differentiation-related proteins expression in human colorectal cancer tissues was evaluated. Results of our study showed that ATO induced the formation of PGCCs, and the daughter cells derived from PGCCs gained a mesenchymal phenotype and exhibited strong migration, invasion, and proliferation abilities. PGCCs also produced embryonic hemoglobin-delta and -zeta with strong oxygen-binding ability and erythroid differentiation-related proteins after ATO treatment. In addition, cell fusion was observed during the formation of PGCCs, indicated by the presence of yellow fluorescence via the GCM1/syncytin-1 signaling pathway. Clinically, the expression of cell fusion-related and erythroid differentiation-related proteins gradually increased with the progression of human colorectal cancer tissues. In conclusion, ATO can promote tumor progression by inducing the formation of PGCCs via GCM1/syncytin-1-mediated cell fusion. PGCCs can produce daughter cells with high invasion and migration abilities and embryonic hemoglobin with strong oxygen binding ability, promoting survival of tumor cells in a hypoxic microenvironment.

In this paper, low-heat Portland cement (LHC) clinkers were prepared by calcining raw materials at 1350°C for 2.0 hours, 1400°C for 1.0 hour, 1400°C for 1.5 hours, 1400°C for 2.0 hours, 1450°C for 1.0 hour, and 1450°C for 2.0 hours. The clinkers were ground with gypsum to produce LHC. The particle size of periclase was analysed by BSEM. Expansion of LHC pastes due to hydration of periclase was measured. The hydration degree of periclase in LHC pastes was quantitatively determined by XRD internal standard method and BSEM. The results showed that the particle size of periclase was larger when clinkers were calcined at higher temperatures or for longer time. Smaller periclase (2.60 μm) in LHC pastes tended to hydrate faster. As a result, expansion of LHC pastes develops relatively faster. Smaller particle of periclase in clinker tends to result in higher hydration degree of periclase in pastes cured at 20°C for 240 days, and there is a small amount of brucite appearing around periclase. The hydration rate of 4.00 μm periclase particle in cement paste cured at 80°C is obviously faster than that in paste cured at 20°C and 40°C. When cement paste was cured at 80°C for 7 days, the periclase was hydrated for 32.56%. The smaller size periclase (1–3 μm) had fully hydrated when the curing age was 240 days, and a large amount of brucite was produced around the larger periclase particle.

PURPOSE:Three dimensional analysis of the face is required for the assessment of complex changes following surgery, pathological conditions and to monitor facial growth. The most suitable method may be "dense surface correspondence". MATERIALS AND METHODS:This method utilizes a generic facial mesh and "conformation process" to establish anatomical correspondences between two facial images. The aim of this study was to validate the use of conformed meshes to measure simulated maxillary and mandibular surgical movements. The "simulation" was performed by deforming the actual soft tissues of the participant during image acquisition. The study was conducted on 20 volunteers and used 77 facial landmarks pre-marked over six anatomical regions; left cheek, right cheek, left upper lip, philtrum, right upper lip and chin region. Each volunteer was imaged at rest and after performing 5 different simulated surgical procedures using 3D stereophotogrammetry. The simulated surgical movement was determined by measuring the Euclidean distances and the mean absolute x, y and z distances of the landmarks making up the six regions following digitization. A generic mesh was then conformed to each of the aligned six facial 3D images. The same six regions were selected on the aligned conformed simulated meshes and the surgical movement determined by determining the Euclidean distances and the mean absolute x, y and z distances of the mesh points making up the six regions were determined. RESULTS:In all cases the mean Euclidian distance between the simulated movement and conformed region was less than 0.7 mm. For the x, y and z directions the majority of differences in the mean absolute distances were less than 1.0mm except in the x-direction for the left and right cheek regions, which was above 2.0 mm. CONCLUSIONS:This concludes that the conformation process has an acceptable level of accuracy and is a valid method of measuring facial change between two images i.e. pre- and post-surgery. The conformation accuracy is higher toward the center of the face than the peripheral regions.

The system NaLa(MoO4)2:Eu3+/Sm3+ phosphors were prepared by solid-state reaction followed by heat treatment at 450–600 °C. As shown by X-ray powder diffraction, the phosphors had a body-centered tetragonal structure, high phase purity and high crystallinity. The photoluminescence measurements carried out under excitation at 464 nm indicated the main emission at about 615 nm corresponding to the electric dipole transition 5D0→7F2 of Eu3+, which agreed well with the emission wavelengths of the GaN-based blue LED chips. In NaLa(MoO4)2:Eu3+/Sm3+ phosphors, Sm3+ can efficiently transfer excitation energy to Eu3+, which resulted in a significant improvement of the fluorescence intensity, and the fluorescence intensity of the phosphors calcined at 550 °C maximized at the doping concentrations of Eu3+ and Sm3+ of 15.0 and 2.0 mol %, respectively. The decay curves and CIE (Commission Internationale de L’ Eclairage) coordinates of Sm3+ or/and Eu3+ doped phosphors were analyzed for the investigation of the energy transfer mechanism and color variation trend. Thus, NaLa(MoO4)2:Eu3+,Sm3+ can be classified as a potential red-emitting phosphor for white light-emitting diodes (WLEDs).

Can non-clinicians spot preschoolers likely to have autism spectrum disorder by observing their everyday peer interaction? We set out to develop a screening tool that capitalizes on peer interaction as a naturalistic "stress test" to identify children more likely than their peers to have autism spectrum disorder. A total of 304 3- to 4-year-olds were observed at school with an 84-item preliminary checklist; data-driven item reduction yielded a 13-item Classroom Observation Scale. The Classroom Observation Scale scores correlated significantly with Autism Diagnostic Observation Schedule--2 scores. To validate the scale, another 322 2- to 4-year-olds were screened using the Classroom Observation Scale. The screen-positive children and randomly selected typically developing peers were assessed for autism spectrum disorder 1.5years later. The Classroom Observation Scale as used by teachers and researchers near preschool onset predicted autism spectrum disorder diagnoses 1.5years later (odds ratios=14.6 and 6.7, respectively). This user-friendly 13-item Classroom Observation Scale enables teachers and healthcare workers with little or no clinical training to identify, with reliable and valid results, preschoolers more likely than their peers to have autism spectrum disorder.

Background: Percutaneous cholecystostomy (PC) is a therapeutic intervention for acute cholecystitis. The benefits of cholecystostomy have been demonstrated in the medical literature, with up to 90% of acute cholecystitis cases shown to resolve postoperatively, and only 40% of patients subsequently undergoing an interval cholecystectomy. Purpose: To compare the survival outcomes between acute complicated and uncomplicated cholecystitis in patients undergoing PC as an initial intervention, as there is a paucity of evidence in the literature on this perspective. Material and Methods: A retrospective search was conducted of all patients who underwent PC for acute cholecystitis between August 2016 and December 2020 at a tertiary institution. A total of 100 patients were included in this study. Results: The outcome, in the form of 30-day mortality, 90-day mortality, being alive after six months, and reintervention, was compared between complicated and uncomplicated cases using the chi-square test or Fisher's exact test. There was no statistically significant difference in any of the compared outcomes. The only variable that showed a statistically significant association with the risk of mortality was acute kidney injury (AKI) at admission. Patients who had stage 1, 2, or 3 AKI had a higher hazard for mortality as compared to patients with no kidney disease. Conclusion: Our results demonstrate that PC is a safe and effective procedure. Mortality is not affected by the presence of complications. The results have, however, highlighted the importance of recognizing and treating AKI, an independent risk factor affecting mortality. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.

We have recently shown that Natural Killer (NK) cells control survival and differentiation of Cancer Stem-like Cells (CSCs) through two distinct phenotypes of cytotoxic and anergic NK cells, respectively. In this report, brain CSCs and their serum and NK cell differentiated counterparts were studied. Serum-differentiated brain CSCs were significantly less susceptible to NK cells and CTL direct cytotoxicity as well as NK cell mediated Antibody Dependent Cellular Cytotoxicity (ADCC), whereas their CSCs were highly susceptible. The levels of CD44 and EGFR were higher in brain tumor CSCs when compared to the serum-differentiated tumors. No differences could be observed for the expression of MHC class I between brain tumor stem cells and their serum-differentiated counterparts. Moreover, supernatants from the combination of IL-2 and anti-CD16mAb treated NK cells (anergized NK cells) induced resistance of brain tumor CSCs to NK cell mediated cytotoxicity. Unlike serum-differentiated CSCs, NK supernatant induced differentiation and resistance to cytotoxicity in brain CSCs correlated with the increased expression of CD54 and MHC class I. The addition of anti-MHC class I antibody moderately inhibited NK mediated cytotoxicity against untreated or serum-differentiated CSCs, whereas it increased cytotoxicity against NK supernatant differentiated tumors. Therefore, two distinct mechanisms govern serum and NK supernatant mediated differentiation of brain tumors.