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Objective: The aim of this study is to identify a rapid, sensitive, and non-destructive auxiliary approach for postmortem diagnosis of SCD, addressing the challenges faced in forensic practice. Methods: ATR-FTIR spectroscopy was employed to collect spectral features of blood samples from different cases, combined with pathological changes. Mixed datasets were analyzed using ANN, KNN, RF, and SVM algorithms. Evaluation metrics such as accuracy, precision, recall, F1-score and confusion matrix were used to select the optimal algorithm and construct the postmortem diagnosis model for SCD. Results: A total of 77 cases were collected, including 43 cases in the SCD group and 34 cases in the non-SCD group. A total of 693 spectrogram were obtained. Compared to other algorithms, the SVM algorithm demonstrated the highest accuracy, reaching 95.83% based on spectral biomarkers. Furthermore, by combing spectral biomarkers with age, gender, and cardiac histopathological changes, the accuracy of the SVM model could get 100%. Conclusion: Integrating artificial intelligence technology, pathology, and physical chemistry analysis of blood components can serve as an effective auxiliary method for postmortem diagnosis of SCD. [ABSTRACT FROM AUTHOR]

Simple Summary: The duration of pupa development on a cadaver holds the potential for estimating the time of colonization (TOC), which is often correlated with the postmortem interval (PMI) of decomposed bodies. Establishing an objective, precise, and efficient method for inferring pupa age has become paramount in forensic entomology. In this study, we observed temporal variations in the reflection spectrum of Chrysomya megacephala (Diptera: Calliphoridae) pupa, detectable through hyperspectral imaging (HSI). Additionally, we proposed that the eXtreme Gradient Boosting Regression (XGBR) model represents an optimal approach for estimating pupa development time based on HSI data. Estimating the age of pupa during the development time of the blow fly Chrysomya megacephala (Diptera: Calliphoridae) is of forensic significance as it assists in determining the time of colonization (TOC), which could help to determine the postmortem interval (PMI). However, establishing an objective, accurate, and efficient method for pupa age inference is still a leading matter of concern among forensic entomologists. In this study, we utilized hyperspectral imaging (HSI) technology to analyze the reflectance changes of pupa development under different temperatures (15 °C, 20 °C, 25 °C, and 30 °C). The spectrograms showed a downtrend under all temperatures. We used PCA to reduce the dimensionality of the spectral data, and then machine learning models (RF, SVR-RBF, SVR-POLY, XGBR, and Lasso) were built. RF, SVR with RBF kernel, and XGBR could show promise in accurate developmental time estimation using accumulated degree days. Among these, the XGBR model consistently exhibited the most minor errors, ranging between 3.9156 and 7.3951 (MAE). This study has identified the value of further refinement of HSI in forensic applications involving entomological specimens, and identified the considerable potential of HSI in forensic practice. [ABSTRACT FROM AUTHOR]

Background: Heat tolerance is a distinct abiotic factor affecting the distribution and abundance of insects. Gut microbiota can contribute to host fitness, thereby increasing resistance to abiotic stress conditions. In this study, Sarcophaga peregrina is closely associated with human life in ecological habits and shows remarkable adaptability to daily and seasonal temperature fluctuations. To date, the role of gut microbiota in S. peregrina response to heat stress and its influence on the host phenotypic variability remain poorly studied. Methods: We exposed S. peregrina to heat stress at 40 °C for 3 h every day throughout the developmental stages from newly hatched larva to adult, after which gut DNA was extracted from third-instar larvae, early pupal stage, late pupal stage, and newly emerged adults, respectively. Then, 16S rRNA microbial community analyses were performed. Results: Firstly, we analyzed whether heat stress could have an impact on the life history traits of S. peregrina and showed that the growth rate of larvae was higher and the developmental time was significantly shorter after heat stress. We then proposed the role of the gut microbiota in the heat tolerance of S. peregrina, which indicated that the bacterial abundance and community structure changed significantly after heat tolerance. In particular, the relative abundance of Wohlfahrtiimonas and Ignatzschineria was higher in the third-instar larval larvae; the former increased and the latter decreased significantly after heat stress. To further explore the effect of disturbing the microbial community on thermotolerant phenotype, newly hatched larvae were fed with amikacin under heat stress, which indicated that the larval length and the whole developmental cycle was significantly shorter. Conclusion: This study indicated that Wohlfahrtiimonas and Ignatzschineria should play an important role in the post-feeding stage under heat stress, but further study is still needed. In general, heat tolerance can affect the gut microbial community structure, which in turn affects the fitness of the host. [ABSTRACT FROM AUTHOR]

As a part of breast-conserving therapy (BCT), postoperative radiotherapy is one of the main means to improve the clinical efficacy of breast cancer (BCa). However, ionizing radiation (IR) may induce BCa cells to develop radioresistance, which causes tumor recurrence and metastasis after treatment. Recently, DOC-2/DAB2 interactive protein (DAB2IP) has been reported often down-regulated in a variety of cancers and is related to tumor tolerance to radiotherapy. In this study, BCa cell lines were introduced to study how DAB2IP deficient influenced BCa cell radiosensitivity in vitro and in vivo and discuss the possible mechanism. Small RNA interference system (siRNA) was employed to decrease DAB2IP expression in two BCa cell lines, MDA-MB-231 and 4T1. Cells in response to IR or antineoplastics were detected by clone formation assay or MTT method, respectively. For in vivo studies, siDAB2IP or siControl cells were subcutaneously injected into the right flank of each female mouse. Sphere formation assay, soft agar colony anchoring assay and in vivo tumorigenesis assay were implemented to examine the stem cell-like features of BCa cells. Tube formation assay as well as immunofluorescence assay (IFA) were respectively applied to determine the angiogenesis of tumor cells in vitro and in vivo. The expression of a series of angiogenesis-related molecules was analyzed by qRT-PCR, western blot and IFA. It was observed that the downregulation of DAB2IP could significantly improve the clone formation ability of BCa cells, reduce their sensitivity to radiation and chemotherapy drugs, enhance their migration and invasion abilities and increase their stemness characteristics. It was also noted that either DAB2IP-knocking down or treated with the conditioned medium from DAB2IP-deficient BCa cells could promote the tube-forming ability of the endothelial cell. Similarly, in vivo studies showed that tumors developed from siDAB2IP BCa cells had higher tumor microvascular density (MVD) and more severe oxygen deficiency than that in DAB2IP- sufficient tumors. Meanwhile, Knock-down of DAB2IP inhibited vascular maturation and promoted the formation of vasculogenic mimicry (VM) in BCa tissues. Down-regulation of STAT3 could enhance siDAB2IP cells sensitivity to IR, accompanied by the decrease of VEGF expression. Our data support that loss of DAB2IP confers radio-resistance of BCa could be due to increased hypoxia, inhibited vascular maturation and promoted VM formation. STAT3 inhibition could be a potential way to overcome such DAB2IP-deficient induced tolerance in BCT. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcophaga crassipalpis Macquart, 1839 (Diptera: Sarcophagidae) is a flesh fly species of medical, veterinary, and forensic importance. It is often used in the laboratory for several biological studies. In the current research, we investigate its life history under changing temperatures ranging from 15.7 to 31.1 °C, with an average of 24.55 °C, and the relative humidity ranges from 31.4 to 82.8% and at six fixed temperatures of 15, 20, 25, 30, 32, and then 35 °C. Also, pteridine from the head was used to assess adult age grading. Our results revealed that the life history and development rate of S. crassipalpis under changing temperatures were very close to those observed at a fixed temperature of 25 °C. The longest and shortest growing times were found at a low rearing temperature of 15 °C and higher temperature of 32 °C, respectively. The pattern of pteridine increase differed depending on the temperature. By employing a changing temperature model in the current study, we aim to provide information on the life history of S. crassipalpis that will be useful in future research. Flesh flies (Diptera: Sarcophagidae) are regarded as significant in medical and veterinary entomology, and their development models can be utilized as considerable markers to ascertain the minimum postmortem interval (PMImin). In this research, we explored the growth cycle and larval body length of Sarcophaga crassipalpis Macquart 1839 (Diptera: Sarcophagidae) reared under variable temperatures ranging from 15.7 to 31.1 °C, with an average of 24.55 °C and relative humidity ranges from 31.4 to 82.8% and at six fixed temperatures of 15, 20, 25, 30, 32, and then 35 °C. Moreover, pteridine from the head was used to assess adult age grading. Our results allowed us to provide three development models: the isomorphen chart, the isomegalen chart, and the thermal summation models. The time taken for S. crassipalpis to complete its development from larviposition to adult emergence at constant temperatures of 15, 20, 25, 30, 32, and 35 °C was 1256.3 ± 124.2, 698.6 ± 15.1, 481.8 ± 35.7, 366.0 ± 13.5, and 295.8 ± 20.5 h, respectively, except 35 °C, where all pupae were unable to attain adulthood. They lasted 485.8 ± 5.4 h under variable temperatures. The minimum developmental limit (D0) temperature and the thermal summation constant (K) of S. crassipalpis were 9.31 ± 0.55 °C and 7290.0 ± 388.4 degree hours, respectively. The increase in pteridine content exhibited variations across different temperatures. There was quite a considerable distinction in the pteridine contents of male and female S. crassipalpis at 15 °C (p = 0.0075) and 25 °C (p = 0.0213). At 32 °C and variable temperatures, the pteridine content between female and male S. crassipalpis was not statistically divergent. However, temperature and gender remain the main factors influencing the pteridine content in the head of S. crassipalpis. We aim to provide detailed developmental data on S. crassipalpis that can be used as a valuable resource for future research and PMI estimation. [ABSTRACT FROM AUTHOR]

Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFα and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment. • HMGN1 and 3M-052 synergistically induce DC maturation and promote its ability to produce TNF-α and IL-12. • HMGN1 and 3M-052 stimulated DCs vaccines combined with anti-TNFR2 effectively inhibits the growth of murine colon cancer. • The combination of HMGN1 and 3M-052 stimulated DCs vaccines with anti-TNFR2 activated the antitumor immune response. • HMGN1 and 3M-052 May have potential as adjuvants for DC-based immunotherapy. • TNFR2 can be used as a new target for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC. [ABSTRACT FROM AUTHOR]

As our study showed, the PLS, SVR, and ANN models based on I S. peregrina i puparial hydrocarbons could be used to estimate the weathering time of the empty puparium. In this study, the results indicated that the hydrocarbon of I S. peregrina i puparium changed with weathering time, which is consistent with that of Zhu (2007), who found that puparial hydrocarbons of I C. megacephala i could be used as an indicator of PMI [[11]]. Keywords: Sarcophaga peregrina; hydrocarbon; PMI; ANN EN Sarcophaga peregrina hydrocarbon PMI ANN N.PAG N.PAG 10 09/27/22 20220901 NES 220901 1. [Extracted from the article]

Ferulic acid (FA) is a natural methylated phenolic acid which represents various bioactivities. Bioproduction of FA suffers from insufficient methyl donor supplement and inefficient hydroxylation. To overcome these hurdles, we first activate the S -adenosylmethionine (SAM) cycle in E. coli by using endogenous genes to supply sufficient methyl donor. Then, a small protein Fre is introduced into the pathway to efficiently regenerate FADH 2 for the hydroxylation. Remarkably, regeneration of these two cofactors dramatically promotes FA synthesis. Together with decreasing the byproducts formation and boosting precursor supply, the titer of FA reaches 5.09 g/L under fed-batch conditions, indicating a 20-fold improvement compared with the original producing E. coli strain. This work not only establishes a promising microbial platform for industrial level production of FA and its derivatives, but also highlights a convenient and effective strategy to enhance the biosynthesis of chemicals requiring methylation and FADH 2 -dependent hydroxylation. • Regeneration of cofactors promoted the efficiency of methylation and hydroxylation. • A highly specific HpaBC was screened for reducing the byproduct formation. • The engineered strain produced highest titer with 5.09 g/L FA in fed-batch fermenter. [ABSTRACT FROM AUTHOR]

Objective. Molecular hydrogen (H2) has been considered a potential therapeutic target in many cancers. Therefore, we sought to assess the potential effect of H2 on colorectal cancer (CRC) in this study. Methods. The effect of H2 on the proliferation and apoptosis of RKO, SW480, and HCT116 CRC cell lines was assayed by CCK-8, colony formation, and flow cytometry assays. The effect of H2 on tumor growth was observed in xenograft implantation models (inhalation of 67% hydrogen two hours per day). Western blot and immunohistochemistry analyses were performed to examine the expression of p-PI3K, PI3K, AKT, pAKT, and SCD1 in CRC cell lines and xenograft mouse models. The expression of SCD1 in 491 formalin-fixed, paraffin-embedded CRC specimens was investigated with immunochemistry. The relationship between SCD1 status and clinicopathological characteristics and outcomes was determined. Results. Hydrogen treatment suppressed the proliferation of CRC cell lines independent of apoptosis, and the cell lines showed different responses to different doses of H2. Hydrogen also elicited a potent antitumor effect to reduce CRC tumor volume and weight in vivo. Western blot and IHC staining demonstrated that H2 inhibits CRC cell proliferation by decreasing pAKT/SCD1 levels, and the inhibition of cell proliferation induced by H2 was reversed by the AKT activator SC79. IHC showed that SCD1 expression was significantly higher in CRC tissues than in normal epithelial tissues (70.3% vs. 29.7%, p = 0.02) and was correlated with a more advanced TNM stage (III vs. I + II ; 75.9% vs. 66.3%, p = 0.02), lymph node metastasis (with vs. without; 75.9% vs. 66.3%, p = 0.02), and patients without a family history of CRC (78.7% vs. 62.1%, p = 0.047). Conclusion. This study demonstrates that high concentrations of H2 exert an inhibitory effect on CRC by inhibiting the pAKT/SCD1 pathway. Further studies are warranted for clinical evaluation of H2 as SCD1 inhibitor to target CRC. [ABSTRACT FROM AUTHOR]

[Display omitted] • The empty puparium can be used for insect species identification. • The biological fingerprint region (1800–1300 cm−1) is considered the most effective for identifying insect species using empty pupariums. • Support Vector Machines offer distinct advantages in species identification, demonstrating 100% accuracy across multiple spectral bands. Accurate identification of insect species holds paramount significance in diverse fields as it facilitates a comprehensive understanding of their ecological habits, distribution range, and impact on both the environment and humans. While morphological characteristics have traditionally been employed for species identification, the utilization of empty pupariums for this purpose remains relatively limited. In this study, ATR-FTIR was employed to acquire spectral information from empty pupariums of five fly species, subjecting the data to spectral pre-processing to obtain average spectra for preliminary analysis. Subsequently, PCA and OPLS-DA were utilized for clustering and classification. Notably, two wavebands (3000–2800 cm−1 and 1800–1300 cm−1) were found to be significant in distinguishing A. grahami. Further, we established three machine learning models, including SVM, KNN, and RF, to analyze spectra from different waveband groups. The biological fingerprint region (1800–1300 cm−1) demonstrated a substantial advantage in identifying empty puparium species. Remarkably, the SVM model exhibited an impressive accuracy of 100 % in identifying all five fly species. This study represents the first instance of employing infrared spectroscopy and machine learning methods for identifying insect species using empty pupariums, providing a robust research foundation for future investigations in this area. [ABSTRACT FROM AUTHOR]

Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae), is a blowfly species widely studied in medical, veterinary, and entomological research. Our study examined the impact of constant (15, 20, 25, 30, and 35 °C) and variable (ranging from 21.0 to 25.4 °C, with an average of 23.31 °C) temperatures on the development and larval body length of C. megacephala. Additionally, we analyzed the age of the adult C. megacephala through pteridine content and related metabolic genes analysis. Our findings revealed three distinct growth patterns: isomorphen diagram, isomegalen diagram, and thermal accumulated models. At constant temperatures of 15, 20, 25, 30, and 35 °C, egg-hatching times were 44.5 ± 8.9, 26.7 ± 4.6, 12.6 ± 1.1, 11.0 ± 1.0, and 9.9 ± 1.9 h, respectively, while it was 15.3 ± 5.9 h at variable temperatures. The total development times from oviposition to adult eclosion in C. megacephala required 858.1 ± 69.2, 362.3 ± 5.9, 289.6 ± 17.8, 207.3 ± 9.3, and 184.7 ± 12.1 h at constant temperatures of 15, 20, 25, 30, and 35 °C, respectively. This duration was extended to 282.0 ± 64.1 h under variable temperatures. However, no significant differences were found in hatching times and the total developmental durations between 25 °C and variable temperatures. A developmental threshold temperature (D 0) of 9.90 ± 0.77 °C and a thermal summation constant (K) of 4244.0 ± 347.0° hours were ascertained. Pteridine content patterns varied significantly across constant temperatures, but not between 25 °C and variable temperatures. Sex and temperature were identified as the primary factors influencing pteridine levels in the head of C. megacephala. Gene expression associated with pteridine metabolism decreased following adult eclosion, matching with increased pteridine concentration. Further investigations are needed to explore the use of pteridine cofactors for age-grading adult necrophagous flies. These findings provide valuable insights into the lifespan of C. megacephala , thereby offering valuable groundwork for forthcoming investigations and PMImin determination. • No significant differences in development times were found between 25 °C and VT. • Pteridine concentration increased following adult eclosion in all temperatures. • Dhpr , PTS , and TH decreased following adult eclosion in all temperatures. [ABSTRACT FROM AUTHOR]

The subfamily Sarcophaginae is extremely diverse in morphology, habit and geographical distribution, and usually considered to be of significant ecological, medical, and forensic significance. In the present study, 18 mitochondrial genomes (mitogenomes) of sarcophagid flies were first obtained. The rearrangement and orientation of genes were identical with that of ancestral insects. The degrees of compositional heterogeneity in the datasets were extremely low. Furthermore, 13 protein-coding genes were evolving under purifying selection. The phylogenic relationship of the genus-group taxa Boettcheria + (Sarcophaga + (Peckia + (Ravinia + Oxysarcodexia))) was strongly supported. Four subgenera were recovered as monophyletic (Liopygia , Liosarcophaga , Pierretia , Heteronychia) in addition to Parasarcophaga as polyphyletic. The sister-relationships between S. dux and S. aegyptiaca , S. pingi and S. kawayuensis were recovered, respectively. Moreover, the molecular phylogenetic relationships among the subgenera Helicophagella , Kozlovea , Kramerea , Pandelleisca , Phallocheira , Pseudothyrsocnema , Sinonipponia and Seniorwhitea were rarely put forward prior to this study. This study provides insight into the population genetics, molecular biology, and phylogeny for the subfamily Sarcophaginae, especially for the subgeneric classification of Sarcophaga. However, compared with the enormous species diversity of flesh flies, the available mitogenomes are still limited for recovering the phylogeny of Sarcophaginae. [ABSTRACT FROM AUTHOR]

Multicolor emitting phosphors LiBaPO4:RE (RE = Eu2+, Tb3+, Sm3+) reported as interesting down-conversion luminescent materials in white light-emitting diodes (w-LEDs) have been prepared by a conventional solid-state reaction. The excitation and emission spectra indicate that these phosphors can be effectively excited by the near-UV light, and emit blue, green, and red light, respectively. The photoluminescence properties, decay times, and Commission Internationale de I'Eclairage (CIE) chromaticity indexes are determined for various concentrations of the activators Eu2+, Tb3+, and Sm3+ in LiBaPO4 host. Furthermore, the temperature-dependent luminescence of these phosphors was investigated. The emission intensities of Tb3+- and Sm3+-doped LiBaPO4 increased unexpectedly with increasing temperature. This interesting phenomenon is proposed to be the result of two ground states in the configurational coordination diagram. The present investigation suggests that LiBaPO4:RE (RE = Eu2+, Tb3+, Sm3+) were potential candidates for application in w-LEDs. [ABSTRACT FROM AUTHOR]

A secondary bacterial infection of the influenza virus in the lungs is a key cause of exacerbation and death. The pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the destruction of the physical barrier of the airways and the dysregulation of the immune response. This article will review the progress of the mechanism of secondary bacterial infection of influenza virus and provide strategies for preventing the co-infection of influenza virus and bacteria. [ABSTRACT FROM AUTHOR]

Aims To investigate whether immunohistochemistry (IHC) could be used to screen BRAF mutation status in formalin-fixed paraffin-embedded (FFPE) colorectal carcinoma (CRC) and papillary thyroid carcinoma (PTC) samples. Methods Eight surgical resected samples, including 2 CRCs with mutated BRAF V600E, 2 PTCs with mutated BRAF V600E, 2 CRCs with wild-type BRAF and 2 PTCs with wild-type BRAF , were selected to explore the optimized IHC conditions for BRAF V600E (VE1) immunostaining using BenchmarkXT automated immunostainer VENTANA Medical System. BRAF V600E status was tested by optimized IHC and ARMS-PCR methods in 255 samples (123 CRCs and 132 PTCs). Sanger sequencing was performed to validate the BRAF V600E status if discordant results were found between optimized IHC and ARMS-PCR methods. Results Antigen retrieval time in 32 min and 64 min showed satisfactory intensity and homogeneity of BRAF V600E staining in CRC and PTC samples, respectively. The concordance between IHC and ARMS/Sanger sequencing was 99.2% (122/123) in CRCs and 96.2% (127/132) in PTCs. In CRCs, the sensitivity of IHC staining for BRAF V600E was 100% (3/3) and the specificity was 99.1% (119/120). In PTCs, the sensitivity was 100% (106/106) and specificity was 80.8% (21/26). The overall concordance across all cases was 97.6% (249/255). Conclusion The appropriate antigen retrieval protocol is critical for accurate analysis of BRAF V600E status by Benchmark XT automated immunostainer. IHC is a suitable method to screen BRAF V600E mutation in FFPE samples of CRCs and PTCs. [ABSTRACT FROM AUTHOR]

Epigenetic modifications serve important roles in non‑small cell lung cancer (NSCLC) tumorigenesis; however, the role of DNA methyltransferase 1 (DNMT1) in lung cancer progression remains unclear. In the present study, the expression of DNMT1 in the human NSCLC cell lines 95D (high invasive ability) and 95C (low invasive ability) was analyzed by western blotting. The results demonstrated that the expression of DNMT1 in 95D cells was significantly higher, compared with in 95C cells and small airway epithelial cells. To further define the role of DNMT1 in tumor migration and invasion in NSCLC cells, RNA interference was used to silence DNMT1 expression. Depletion of DNMT1 significantly inhibited 95D cell invasion and migration. In addition, treatment with DNMT1 small interfering RNA resulted in compact cell morphology and significantly increased epithelial marker E‑cadherin expression whilst also decreasing the expression of certain mesenchymal markers, including vimentin and fibronectin. Suppression of DNMT1 increased cytoplasmic β‑catenin levels while downregulating nuclear β‑catenin and Snail, an important regulator of EMT. The results from the present study suggest that the inhibition of DNMT1 reverses the epithelial‑mesenchymal transition partly via the inhibition of the Wnt/β‑catenin signaling pathway, and therefore inhibits cell migration and invasion. These results indicate that targeting DNMT1 may inhibit tumor metastasis and that DNMT1 is a promising target for the novel treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Aims: The aim of this project was to explore the different CTX-M expression levels occurring from a single conserved promoter with different spacer sequences, the variation of which is hypothesized to be a key factor in fluctuating levels of CTX-M. Methods: The bla CTX-M promoter fragments with five different spacer sequences were amplified, sequenced and cloned into the pUA66 expression vector carrying the green fluorescent protein (GFP) gene. The expression of blaC TX-M in the transconjugants was analyzed using fluorescence microscopy, flow cytometry and qRT-PCR. Results: The promoters of all the b laC TX-M genes were provided by IS Ecp1 and were extremely conserved. The promoter-associated spacer sequences varied from 42 to 127 bp and variations in GFP expression in the five transconjugants were observed. A nucleic acid deletion and point mutation were detected in the spacer sequences by variations in which the expression of bla CTX-M was influenced. Conclusion: The dif-ferent spacer sequences have a significant impact on the activity of the conserved promoter. The shorter spacer sequence between the conserved promoter and the bla CTX-M gene does not specifically enhance the expression of blaCTX-M, contrary to previous reports. The expression of bla CTX-M may be regulated by changes in promoter activity caused by diverse spacer sequences. [ABSTRACT FROM AUTHOR]

Abstract: Novel LiSrPO4:Dy3+ phosphors for white light-emitting diodes (w-LEDs) were synthesized by the conventional solid-state reaction. X-ray powder diffraction (XRD) analysis confirmed the phase formation of LiSrPO4:Dy3+ materials. Luminescence properties results showed that the phosphor could be efficiently excited by the UV–vis light region from 250 to 460nm, and it exhibited blue (483nm) and yellow (574nm) emission corresponding to 4F9/2 → 6H15/2 transitions and 4F9/2 → 6H13/2 transitions, respectively. The luminescence intensity of LiSrPO4:xDy3+ phosphor firstly increased and then decreased with increasing Dy3+ concentration, and reached the maximum at x =0.03. It was found that concentration quenching occurred as a result of dipole-dipole interaction according to the Dexter''s theory. The decay time was also determined for various concentrations of Dy3+ in LiSrPO4. [Copyright &y& Elsevier]

Simple Summary: Forensic entomology plays a major role in postmortem interval (PMI) estimation, mainly based on morphological characteristics of larvae colonized on decomposed corpses. However, weight and length cannot be used as relevant parameters to calculate the age of wandering at the larval and pupal stages. In order to identify a specific indicator that may serve as a potential target, studies on the mechanism during postembryonic development may provide a foundation to establish a molecular age determination method. Sarcophaga peregrina (Robineau-Desvoidy, 1830) is a species of medical and forensic importance. In this study, transcriptome analysis was performed to investigate gene expression profiles from the larval to pupal stages of S. peregrina, which were used to identify differentially expressed genetic markers as candidates for molecular age estimation. This study explores molecular mechanisms during postembryonic development of S. peregrina. The developmental, stage-specific gene profiles suggest genetic markers for age prediction of forensically important flies. Sarcophaga peregrina (Robineau-Desvoidy, 1830) is a species of medical and forensic importance. In order to investigate the molecular mechanism during postembryonic development and identify specific genes that may serve as potential targets, transcriptome analysis was used to investigate its gene expression dynamics from the larval to pupal stages, based on our previous de novo-assembled genome of S. peregrina. Totals of 2457, 3656, 3764, and 2554 differentially expressed genes were identified. The specific genes encoding the structural constituent of cuticle were significantly differentially expressed, suggesting that degradation and synthesis of cuticle-related proteins might actively occur during metamorphosis. Molting (20-hydroxyecdysone, 20E) and juvenile (JH) hormone pathways were significantly enriched, and gene expression levels changed in a dynamic pattern during the developmental stages. In addition, the genes in the oxidative phosphorylation pathway were significantly expressed at a high level during the larval stage, and down-regulated from the wandering to pupal stages. Weighted gene co-expression correlation network analysis (WGCNA) further demonstrated the potential regulation mechanism of tyrosine metabolism in the process of puparium tanning. Moreover, 10 consistently up-regulated genes were further validated by qRT-PCR. The utility of the models was then examined in a blind study, indicating the ability to predict larval development. The developmental, stage-specific gene profiles suggest novel molecular markers for age prediction of forensically important flies. [ABSTRACT FROM AUTHOR]

Sarcophaga dux (Diptera: Sarcophagidae) is a necrophagous flesh fly species with potential forensic value for estimating minimum postmortem interval (PMI min). The basic developmental data and precise age estimates of the pupae are significant for PMI min estimation in forensic investigations. In the present study, we investigated the development data of that species at seven constant temperatures varying from 16 °C to 34 °C, including body length changes of the larve, developmental duration and accumulated degree hours of the preadults. Several reference genes for relative quantification of the differentially expressed genes (DEGs) were firstly selected and evaluated in the pupae of different ages under different temperatures. The DEGs of the insects during the pupal period at different constant temperatures (34, 25 and 16 °C) were further analyzed for more precise age estimation. The results showed that the developmental durations of the preadults at 16, 19, 22, 25, 28, 31 and 34 °C were 1478.6 ± 18.3 h, 726.1 ± 15.8 h, 538.5 ± 0.9 h, 394.1 ± 9.5 h, 375.6 ± 10.8 h, 284.1 ± 7.3 h, and 252.5 ± 6.1 h, respectively. The developmental threshold temperature the flies was 12.27 ± 0.35 °C, and the thermal summation constant was 5341.71 ± 249.29° hours. The most reliable reference genes during the pupal period at different temperatures were found: GST1 and 18S rRNA for the 34 °C group, GST1 and RPL49 for 25 °C, and 18S rRNA and 28S rRNA for 16 °C. The four differential expression genes (Hsp60 , A-alpha , ARP , and RPL8) have the potential to be used for more precise age estimation of pupal S. dux. This work provides important basic developmental data and a more precise age estimation method for pupal S. dux , and improves the value of this species for PMI min estimation in forensic investigations. Image 1 • The basic developmental data of S. dux during different temperatures were collected. • Four appropriate reference genes at intrapuparial stage of S. dux were selected. • The expression patterns of the same DEGs at the three temperature regimes (34°C, 25°C and 16°C) were similar. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. Methods: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. Results: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. Conclusions: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is frequently associated with oncogenic driver mutations, which play an important role in carcinogenesis and cancer progression. Targeting epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements has become standard therapy for patients with these aberrations because of the greater improvement of survival, tolerance, and quality-of-life compared to chemotherapy. Clinical trials for emerging therapies that target other less common driver genes are generating mixed results. Here, we review the literature on rare drivers in NSCLC with frequencies lower than 5% (e.g., ROS1, RET, MET, BRAF, NTRK, HER2, NRG1, FGFR1, PIK3CA, DDR2, and EGFR exon 20 insertions). In summary, targeting rare oncogenic drivers in NSCLC has achieved some success. With the development of new inhibitors that target these rare drivers, the spectrum of targeted therapy has been expanded, although acquired resistance is still an unavoidable problem. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a unique type of gastric carcinomas that promoter hypermethylation of tumor-related genes is extremely frequent to be found. Aquaporin 3 (AQP3) is a small membrane transport protein that plays a crucial role in cancer progression and metastasis. However, there is no experimental study on the expression of AQP3 in EBVaGC and the regulation mechanism of EBV on AQP3. In this study, the loss of AQP3 was contributed by the hypermethylation status of AQP3 promoter in EBVaGC which was caused by elevated expression of DNMT3a. In addition, stable and transient transfection system in SGC7901 showed that viral latent membrane protein 2A (LMP2A) activated phosphorylated ERK and up-regulated DNMT3a. Taken together, LMP2A induced the phosphorylation of ERK, which activated DNMT3a transcription and caused AQP3 expression loss through CpG island methylation of AQP3 promoter in EBVaGC. [ABSTRACT FROM AUTHOR]

Background: Multidrug‐resistant tuberculosis (MDR‐TB) brings major challenges to the health care workers (HCWs). This study is to determine the risk factors for MDR‐TB, latent tuberculosis infection (LTBI), and tuberculosis (TB) disease among HCWs in China. Methods: A meta‐analysis was conducted to evaluate the risk factors for MDR‐TB, LTBI, and TB disease among HCWs using a random‐effects model, and the pooled odds ratios (ORs) with 95% confidence interval (CI) were used as effect indicators. Results: We identified 46 eligible studies and found eight factors were associated with MDR. The ORs with 95% CI are migrant population 1.96 (95% CI, 1.50–2.57), low family income 2.23 (95% CI, 1.74–2.85), retreatment 7.22 (95% CI, 5.63–9.26), anti‐TB treatment history 5.65 (95% CI, 4.80–6.65), multiple episodes of treatment 3.28 (95% CI, 2.60–4.13), adverse reactions 3.48 (95% CI, 2.54–4.76), interrupted treatment 3.18 (95% CI, 2.60–3.89), and lung cavities 1.42 (95% CI, 1.14–1.77). Work duration as a HCW for 5 years and above increased the risk of LTBI and TB. HCWs aged 30 years and above were more susceptible to TB (OR = 1.70, 95% CI: 1.37–2.09). Conclusion: The risk factors for MDR‐TB in China are possibly migrant population, low family income, retreatment, anti‐TB treatment history, adverse reactions, interrupted treatment, and lung cavities. Longer work duration and greater age are risk factors for LTBI and TB among HCWs. [ABSTRACT FROM AUTHOR]

Background: The flesh fly, Sarcophaga peregrina (Diptera: Sarcophagidae), is an important hygiene pest, that causes myiasis in humans and other mammals, typically livestock, and as a vector for various parasitic agents, including bacteria, viruses, and parasites. The role of long non-coding RNAs (lncRNAs) in regulating gene expression during metamorphosis of the flesh fly has not been well established. Methodology/Principal findings: In this study, we performed genome-wide identification and characterization of lncRNAs from the early pupal stage (1-days pupae), mid-term pupal stage (5-days pupae), and late pupal stage (9-days pupae) of S. peregrina by RNA-seq, and a total of 6921 lncRNAs transcripts were identified. RT-qPCR and enrichment analyses revealed the differentially expressed lncRNAs (DE lncRNAs) that might be associated with insect metamorphosis development. Furthermore, functional analysis revealed that the DE lncRNA (SP_lnc5000) could potentially be involved in regulating the metamorphosis of S. peregrina. RNA interference of SP_lnc5000 caused reduced expression of metamorphosis-related genes in 20-hydroxyecdysone (20E) signaling (Br-c, Ftz-F1), cuticle tanning pathway (TH, DOPA), and chitin related pathway (Cht5). Injection of dsSP_lnc5000 in 3rd instar larvae of S. peregrina resulted in deformed pupae, stagnation of pupal-adult metamorphosis, and a decrease in development time of pupal, pupariation rates and eclosion rates. Hematoxylin-eosin staining (H&E), scanning electron microscope (SEM) observation and cuticle hydrocarbons (CHCs) analysis indicated that SP_lnc5000 had crucial roles in the metamorphosis developmental by modulating pupal cuticular development. Conclusions/Significance: We established that the lncRNA SP_lnc5000 potentially regulates the metamorphosis of S. peregrina by putatively affecting the structure and composition of the pupal cuticle. This study enhances our understanding of lncRNAs as regulators of metamorphosis in S. peregrina, and provide valuable insights into the identification of potential targets for vector control and the development of effective strategies for controlling the spread of myiasis and parasitic diseases. Author summary: Sarcophaga peregrina, a significant flesh fly species, is closely associated with human life in its ecological habits, as vectors of parasitic disease agents, they can cause myiasis and other tropical infectious diseases, and has been implicated in the transmission of diseases such as cutaneous leishmaniasis. Enhance the understanding of metamorphosis of this species, have a significance for vector control. The lncRNAs plays important roles in growth development of insect. However, its role in regulating the metamorphosis of S. peregrina has not been reported so far. In this study, we obtained genome-wide identification of lncRNA profiles from different pupae developmental stages of S. peregrina. Furthermore, we performed a functional analysis of differentially expressed lncRNAs (SP_lnc5000) in regulating the metamorphosis of S. peregrina by RNA interference, and H&E staining, SEM observation and CHCs detection. The results provided here increase the knowledge on metamorphosis processes in S. peregrina, which is important for the design of new vector control strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Constant and fluctuating temperatures can affect the growth and development of insects, which will affect the accuracy of minimum postmortem interval estimation. Our study found that the development time of S. peregrina was prolonged under fluctuating temperatures. The estimation of the pupal stage has a significant effect on the estimation of PMI. We explored the feasibility of different methods for intra-puparial age estimation and found that the DEG expression profile, ATR-FTIR, and CHCs detection, combined with chemometrics, had the potential to estimate the intra-puparial age of S. peregrina under constant and fluctuating temperatures. Sarcophaga peregrina (Robineau-Desvoidy, 1830) has the potential to estimate the minimum postmortem interval (PMImin). Development data and intra-puparial age estimation are significant for PMImin estimation. Previous research has focused on constant temperatures, although fluctuating temperatures are a more real scenario at a crime scene. The current study examined the growth patterns of S. peregrina under constant (25.75 °C) and fluctuating temperatures (18–36 °C; 22–30 °C). Furthermore, differentially expressed genes, attenuated total reflectance Fourier-transform infrared spectroscopy, and cuticular hydrocarbons of S. peregrina during the intra-puparial period were used to estimate age. The results indicated that S. peregrina at fluctuating temperatures took longer to develop and had a lower pupariation rate, eclosion rate, and pupal weight than the group at constant temperatures did. Moreover, we found that six DEG expression profiles and ATR-FTIR technology, CHCs detection methods, and chemometrics can potentially estimate the intra-puparial age of S. peregrina at both constant and fluctuating temperatures. The findings of the study support the use of S. peregrina for PMImin estimation and encourage the use of entomological evidence in forensic practice. [ABSTRACT FROM AUTHOR]

A large eddy model with detailed chemical reaction mechanism is developed to investigate the interior ballistic process of the combustion light gas gun (CLGG). Flame acceleration and deflagration to detonation transition process with high initial pressure and low initial temperature hydrogen–oxygen mixture in CLGG is numerically studied. Simulation results indicate that the hydrogen–oxygen flame propagation experiences an exponential acceleration stage, a nearly uniform propagation stage and a fast reacceleration stage. Detonation can be triggered through two different mechanisms, which are the amplification between the overlapped shock wave at flame surface, and the elevated flame velocity and shock strength caused by local explosions. Reflected shock waves play an important role in the suppression of the flame propagation when the flame front is close to the chamber throat, leading to a deceleration of the deflagration flame. [ABSTRACT FROM AUTHOR]

In the present study, the self-excited vibrations of an axially retracting beam under gravity is investigated. A GFB method is presented to discretize the system energy functions, in which the orthogonality relationships between the basis functions are needless. In this way, the motion equations can be derived in a much simpler way of matrix. The presented method and the derived motion equations are validated by comparing the computed results with which from previous literature. Based on the computed dynamic responses, the effect of gravity on beam dynamic behavior is investigated. An interesting phenomenon of self-excited vibration is observed as the beam retracts with a certain axial speed. Finally, the effects of retracting speed, structural damping and static tip deflection on self-excited vibration are investigated. [ABSTRACT FROM AUTHOR]

Background : A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. Methods: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. Results: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10−14), ABO rs582094 (p-value = 1.16 × 10−10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10−17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. Conclusions: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development. [ABSTRACT FROM AUTHOR]

Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is a forensically important flesh fly with potential value for estimating the minimum postmortem interval (PMImin). Here, the developmental patterns of S. peregrina were investigated at 5 constant temperatures (15–35 °C). Morphological changes at different developmental stages of the pupa were observed at 4 constant temperatures (15–30 °C) by removing the puparium and staining the pupa with hematoxylin and eosin. Furthermore, differentially expressed genes (DEGs) were analyzed at 25 °C in the intrapuparial period to estimate the age of S. peregrina during the intrapuparial stage. S. peregrina completed development from larviposition to adult eclosion at 15 °C, 20 °C, 25 °C, and 30 °C; the developmental durations were 1090.3 ± 30.6 h, 566.6 ± 21.9 h, 404.6 ± 13.01 h, and 280.3 ± 4.5 h, respectively, while the development could not be completed at 35 °C. The intrapuparial period of S. peregrina was divided into 12 sub-stages on the basis of the overall external morphological changes; 6 sub-stages on the basis of individual morphological structures such as the compound eyes, antennae, thorax, legs, wings, and abdomen; and 10 sub-stages on the basis of internal morphological changes detected using histological analysis. The period of each sub-stage or structure that appeared was determined. Moreover, we found that 6 genes (NDUFS2, CPAMD8, NDUFV2, Hsp27, Hsp23, and TPP) with differential expression can be used for the precise age estimation of S. peregrina during the intrapuparial period. This study provided basic developmental data for the use of S. peregrina in PMImin estimation, and we successfully estimated PMImin in a real forensic case by using a multimethod combination. [ABSTRACT FROM AUTHOR]

Simple Summary: The precise pupal age estimates of S. peregrina are significant for estimating the minimum postmortem interval (PMImin) in forensic investigations. In the present study, we first investigated the potential of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and cuticular hydrocarbons (CHCs) for the age estimations of S. peregrina pupae at different constant temperatures (20 °C, 25 °C, and 30 °C). The orthogonal projections to latent structure discrimination analysis (OPLS-DA) and partial least squares (PLS) models were used to distinguish the pupae samples of different developmental ages. Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is a forensically important flesh fly that has potential value in estimating the PMImin. The precise pupal age estimation has great implications for PMImin estimation. During larval development, the age determination is straightforward by the morphological changes and variation of length and weight, however, the pupal age estimation is more difficult due to anatomical and morphological changes not being visible. Thus, it is necessary to find new techniques and methods that can be implemented by standard experiments for accurate pupal age estimation. In this study, we first investigated the potential of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and cuticular hydrocarbons (CHCs) for the age estimations of S. peregrina pupae at different constant temperatures (20 °C, 25 °C, and 30 °C). The orthogonal projections latent structure discrimination analysis (OPLS-DA) classification model was used to distinguish the pupae samples of different developmental ages. Then, a multivariate statistical regression model, partial least squares (PLS), was established with the spectroscopic and hydrocarbon data for pupal age estimations. We identified 37 CHCs with a carbon chain length between 11 and 35 in the pupae of S. peregrina. The results of the OPLS-DA model show a significant separation between different developmental ages of pupae (R2X > 0.928, R2Y > 0.899, Q2 > 0.863). The PLS model had a satisfactory prediction with a good fit between the actual and predicted ages of the pupae (R2 > 0.927, RMSECV < 1.268). The results demonstrate that the variation tendencies of spectroscopy and hydrocarbons were time-dependent, and ATR-FTIR and CHCs may be optimal for the age estimations of pupae of forensically important flies with implications for PMImin estimation in forensic practice. [ABSTRACT FROM AUTHOR]

Although wear mechanism of gun barrel and projectile-barrel interaction have been comprehensively studied in the past three decades, attention has seldom been paid to the interaction between worn barrel and projectile. In the present work, a new parametric geometric modeling method for gun barrel and a new finite element meshing strategy for the worn barrel are proposed which involve the joint use of Python code and ABAQUS software. A transient coupled thermo-mechanical finite element (FE) model is developed to compute the plastic deformation of rotating band and the performance of interior ballistics. Additionally, material thermal properties of the rotating band are considered and user subroutine VUAMP and VFRICTION are implemented within the FE model in order to take account of the propelling force caused by propellant gas and the effect of changing friction stress, respectively. The FE results obtained in simulation verify the ability of the proposed meshing strategy to improve analysis accuracy with respect to the interaction between the worn barrel and the projectile. [ABSTRACT FROM AUTHOR]

In forensic pathology, traumatic brain injury (TBI) is a frequently encountered cause of death. Unfortunately, the statistic autopsy data, risk investigation about injury patterns, and circumstances of TBI are still sparse. Estimates of survival time post-TBI and postmortem diagnosis of TBI are especially important implications in forensic medicine. Neurogranin (Ng) and myelin basic protein (MBP) represent potential biomarkers of TBI. The present study analyzed retrospectively the forensic autopsy records of TBI cases at a university center of medico-legal investigation from 2008 to 2020. Immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to investigate the expression changes of Ng and MBP in the cortical brain injury adjacent tissues and serum, respectively, from cases of TBI at autopsy with different survival times post-TBI. The results show that the major mechanism of death of TBI is assault, and accident was the major manner of death. Ng and MBP are mainly expressed in the cortical nerve cells and the myelin sheath, respectively. The serum levels of Ng and MBP in each TBI group were higher compared with those in the controls. The brain cortical levels of Ng and MBP decreased at first and then steadily increased with extended survival time post-TBI. The immunopositive ratios and serum concentration of Ng and MBP have shown significant differences among control group and all TBI group (p < 0.001). Collectively, the immunohistochemical analyses of Ng and MBP in human brain tissues may be useful to determine the survival time after TBI, and Ng and MBP level in the human blood specimens could be considered as a postmortem diagnostic tools of TBI in forensic practice. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (SP) is a major cause of community-acquired pneumonia. Ferroptosis pitches in pneumonia. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) regulates ferroptosis in various cells. Therefore, this study probed the mechanism of lncRNA NEAT1 on SP-induced ferroptosis in AECs. Serum lncRNA NEAT1 level in 36 streptococcus pneumonia patients were retrospectively detected, with its correlations with inflammatory factor (TNF-α/IL-1β/IL-6) levels analyzed. Human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with sh-NEAT1 and induced by SP. Cell viability was evaluated by CCK-8. Lactate dehydrogenase (LDH) activity was assessed. Iron content, and levels of TNF-α/IL-1β/IL-6/IL-10/lncRNA NEAT1/lipid peroxidation products [malondialdehyde (MDA)/glutathione (GSH)/reactive oxygen species/(ROS)]/ferroptosis-related proteins [Cyclooxgenase 2 (COX2)/recombinant solute carrier family 7 member 11 (SLC7A11)/total nuclear factor erythroid 2-related factor 2 (Nrf2)/cytoplasmic Nrf2 (C-Nrf2)/nuclear Nrf2 (N-Nrf2)/GPX4)] were determined by kit/ELISA/RT-qPCR/kits/Western blot. Nrf2 nuclear translocation was detected by immunofluorescence assay. On top of lncRNA NEAT1 knockdown, SP-induced HPAEpiC were treated with ML385. Serum lncRNA NEAT1 level was elevated in streptococcus pneumonia patients, and were positively interrelated with TNF-α/IL-1β/IL-6 levels. SP promoted cell HPAEpiC injury and inflammatory response, and up-regulated lncRNA NEAT1 level. LncRNA NEAT1 knockdown suppressed HPAEpiC injury/inflammatory response (reduced LDH activity and TNF-α/IL-1β/IL-6 levels, elevated IL-10) and suppressed ferroptosis (decreased iron/MDA/ROS contents and COX2 level, increased GSH/SLC7A11), facilitated Nrf2 nuclear translocation, and up-regulated GPX4. Nrf2-GPX4 pathway inhibition annulled NEAT1 knockdown-mediated improvement on SP-induced HPAEpiC ferroptosis/injury/inflammatory response. LncRNA NEAT1 knockdown suppressed SP-induced HPAEpiC ferroptosis by activating Nrf2-GPX4 pathway, thereby alleviating cell injury and inflammatory response. [Display omitted] • LncRNA NEAT1 level in Streptococcus pneumoniae pneumonia patients is positively linked with TNF-α, IL-1β, and IL-6 levels. • LncRNA NEAT1 knockout reduces streptococcus pneumoniae-led human pulmonary alveolar epithelial cell injury and inflammation. • LncRNA NEAT1 knockdown represses streptococcus pneumoniae-induced ferroptosis in human pulmonary alveolar epithelial cells. • Silencing lncRNA NEAT1 promotes Nrf2 nuclear translocation and up-regulates GPX4. • Nrf2-GPX4 ferroptosis inhibition annuls the effects of NEAT1 knockout in human pulmonary alveolar epithelial cells. [ABSTRACT FROM AUTHOR]

This document is a retraction note from the journal Cancer Cell International. The article in question, titled "MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells," has been retracted at the request of the corresponding author. Concerns were raised about image overlap between two figures in the article, and the corresponding author stated that they do not have the raw data or evidence for ethics approval. The editors no longer have confidence in the results and conclusions of the article. Some of the authors have agreed to the retraction, while others have not responded to correspondence from the editor/publisher. Springer Nature, the publisher, remains neutral in regards to jurisdictional claims and institutional affiliations. [Extracted from the article]

• Take the lead in combining transformer and VAE for anomaly detection in telemetry data. • Use the improved positional encoding to help transformer capture long-range dependencies. • Apply the proposed multi-scale feature fusion to obtain a more robust feature expression. • A residual structure is proposed, which can alleviate the KL divergence vanishing problem. Due to the strategic importance of satellites, the safety and reliability of satellites have become more important. Sensors that monitor satellites generate lots of multivariate time series, and the abnormal patterns in the multivariate time series may imply malfunctions. The existing anomaly detection methods for multivariate time series have poor effects when processing the data with few dimensions or sparse relationships between sequences. This paper proposes an unsupervised anomaly detection model based on the variational Transformer to solve the above problems. The model uses the Transformer's self-attention mechanism to capture the potential correlations between sequences and capture the multi-scale temporal information through the improved positional encoding and up-sampling algorithm. Then, the model comprehensively considers the extracted features through the residual variational autoencoder to perform effective anomaly detection. Experimental results on a real dataset and two public datasets show that the proposed method is superior to the mainstream and state-of-the-art methods. [ABSTRACT FROM AUTHOR]

We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 − 0.71); specificity 0.72 (0.71 − 0.73), PPV 0.25 (0.24 − 0.26) and NPV 0.94 (0.94 − 0.95). We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504. [ABSTRACT FROM AUTHOR]

Background: The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. Results: Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. Conclusion: The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases. [ABSTRACT FROM AUTHOR]

The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods. [ABSTRACT FROM AUTHOR]

Abstract: Novel blue/green NaSrPO4 phosphors co-doped with Eu2+ and Tb3+ were synthesized by a conventional solid-state reaction. Their luminescent properties were characterized by using powder X-ray diffraction, photoluminescence excitation and emission spectra, lifetime, and temperature dependent emission spectra, respectively. The NaSrPO4:Eu2+,Tb3+,Na+ phosphor showed an intense broad excitation band between 250 and 430nm, which was in agreement with the near-UV chip (350–420nm), and it exhibited two dominating emission bands at 445 and 545nm, corresponding to the allowed 4f65d1→4f7(8S7/2) transition of Eu2+ ion and the 5D4→7F5 transition of Tb3+ ion, respectively. The emission intensity and lifetime of Eu2+ ion decreased with the increasing concentration of Tb3+ ion, which strongly indicated that an effective energy transfer occurred from Eu2+ to Tb3+ in NaSrPO4 host. The principle of the energy transfer should be the combined effect of the non-radiative resonant energy transfer and the phonon-assisted non-radiative process. [Copyright &y& Elsevier]

Abstract: Well-crystallized and regular-shaped BaYF5:Yb3+/Er3+ upconversion (UC) fluorescent nanocrystals (NCs) were synthesized in a modified water–ethanol–oleic acid system. The size and shape of the NCs were controlled by adjusting the amount of NaOH, reaction temperature and time. Well oil-dispersible NCs exhibited bright UC fluorescence under the 980nm excitation. Furthermore, a systematic study on the photoluminescence of Yb3+/Er3+-doped BaYF5 samples with different size and shapes indicated that the optical properties of products were strongly dependent on their size, and the configuration of nanocrystals were found to sensibly affect the optical properties of the products. Great enhancement of the green emission intensity was observed with increasing crystalline size. It was found that the crystalline and surface effects could be responsible for the observation and this behavior was attributed to a change of conditions and the quenching effect of the organic ligands. [ABSTRACT FROM AUTHOR]

• Take the lead in using GNN to complete the task of anomaly detection. • Use the proposed dynamic threshold method to evaluate telemetry data. • Apply the proposed method to convert linear structure data into graph data. • Our model is end-to end, and needs no domain knowledge from experts. To ensure the stable long-time operation of satellites, evaluate the satellite status, and improve satellite maintenance efficiency, we propose an anomaly detection method based on graph neural network and dynamic threshold (GNN-DTAN). Firstly, we build the graph neural network model for telemetry data. The graph construction module in the model extracts the relationship between features, and the spatial dependency extraction module and the temporal dependency extraction module extract the spatial and temporal dependencies of the data, respectively. The trained model is then used to predict the data, and the anomaly score between the predicted and actual values is calculated. Finally, the wavelet variance is used to analyze the data period. A dynamic threshold method based on the period time window is used to detect anomalies in the data set. Experimental results of satellite power system telemetry data show that the proposed algorithm's accuracy reaches more than 98%, with good effectiveness and robustness. [ABSTRACT FROM AUTHOR]

As a bladder-preserving therapy, radiation therapy (RT) has been widely used in the treatment of bladder cancer (BCa) and made great progress in the past few decades. However, some BCa patients have low RT responsiveness and local recurrence rate after RT could reach 50%. Acquired radio-resistance (ARR) is one of the important reasons for the failure of RT. Unfortunately, these ARR cells also lack sensitivity to chemotherapy and cause tumor recurrence and metastasis. To build ARR-phenotype BCa cell model, discuss the possible molecular mechanism of ARR and find effective target molecules to overcome ARR. Five thousand six hundred and thirty-seven cells were subjected 30 times to 2 Gy of γ-rays and the surviving cells were called 5637R. Colony formation and MTT assay were applied to evaluate cells sensitivity to ionizing radiation (IR) and anti-neoplastic agents, respectively. Cells abilities of migration and invasion were determined using transwell method. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot (WB) were respectively utilized to compare the difference of gene and protein expression between 5637 and 5637R cells. Molecule inhibitors and small interfering RNA (siRNA) systems were employed to decrease the expression of target proteins, respectively. BCa cells survived from fractionated irradiation (FI) exhibited tolerance to both IR and chemotherapy drugs. These ARR cells (5637R) had elevated migration and invasion abilities, accompanied by increased expression of epithelial mesenchymal transition (EMT)-related transcription factors (ZEB1/Snail/Twist). Moreover, 5637R cells showed enhanced cancer stem cell (CSC)-like characteristics with activated KMT1A–GATA3–STAT3 circuit, a newly reported self-renewal pathway of human bladder cancer stem cell (BCSC). Combined with Kaplan–Meier's analysis, we speculated that GATA3/MMP9/STAT3 could be an effective molecular panel predicting poor prognosis of BCa. In order to enhance the sensitivity of resistant cells to radiation, we introduced ERK inhibitor (FR 180204) and STAT3 inhibitor (S3I-201). However, both of them could not enhance ARR cells response to IR. On the other hand, siRNAs were respectively implemented to inhibit the expression of endogenous Beclin1 and Atg5, two important autophagy-related genes, in BCa cells, which significantly increased 5637R cells death upon taxol exposing. Similarly, chloroquine (CQ), a classic autophagy inhibitor, enhanced the cytotoxicity of taxol only on 5637R cells. Long-term FI treatment is an effective method to establish the ARR-phenotype BCa cell model, by enriching BCSCs and enhancing cells migration and invasion. Both inhibiting the expression of autophagy-related proteins and using autophagy inhibitor can increase the sensitivity of ARR cells to taxol, suggesting that autophagy may play an important role in ARR cells chemical tolerance. [ABSTRACT FROM AUTHOR]

Various studies demonstrated that bone morphogenetic proteins (BMPs) and their antagonists contribute to the development of cancers. Chordin‐like 2 (CHRDL2) is a member of BMP antagonists. However, the role and its relative mechanism of CHRDL2 in osteosarcoma remains unclear. In the present study, we demonstrated that the expression of CHRDL2 was significantly upregulated in osteosarcoma tissues and cell lines compared with adjacent tissues and human normal osteoblast. Inhibition of CHRDL2 decreased the proliferation and colony formation of osteosarcoma cells in vitro, as well as the migration and invasion. CHRDL2 overexpression induced the opposite effects. CHRDL2 can bind with BMP‐9, thus decreasing BMP‐9 expression and the combination to its receptor protein kinase ALK1. It was predicted that BMP‐9 regulates PI3K/AKT pathways using gene set enrichment analysis. Inhibition of CHRDL2 decreased the activation of PI3K/AKT pathway, while overexpression of CHRDL2 upregulated the activation. Increasing the expression of BMP‐9 reversed the effects of CHRDL2 overexpression on the activation of PI3K/AKT pathway, as well as the proliferation and metastasis of osteosarcoma cells. Take together, our present study revealed that CHRDL2 upregulated in osteosarcoma tissues and cell lines, and promoted osteosarcoma cell proliferation and metastasis through the BMP‐9/PI3K/AKT pathway. CHRDL2 maybe an oncogene in osteosarcoma, as well as novel biomarker for the diagnosis of osteosarcoma. [ABSTRACT FROM AUTHOR]

• Multifunctional CQDs decorated self-healing hydrogel was prepared. • The CQDs exhibited outstanding antibacterial ability against both S. aureus and MRSA. • The CQDs as nanozyme possessed excellent SOD and CAT-like properties. • The immunomodulatory CQDs were able to relieve the detrimental inflammation. • The CQDs/hydrogel platform exhibited great promise for superbug infected wounds. Rapid healing of wounds infected by bacteria, especially multidrug-resistant bacteria, is a common clinical challenge. Local bacterial infection causes excessive reactive oxygen species (ROS) that further induce oxidative stress and inflammatory responses, which impairs cell migration, angiogenesis and delays cutaneous regeneration. Herein, we designed a novel type of carbon quantum dots (CQDs) derived from herbal medicines. The CQDs are able to against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), and possessed SOD-like as well as CAT-like activities for scavenging ROS. The biocompatible CQDs could protect HUVECs migration and angiogenesis from oxidative stress damage. Moreover, the expression of NO and pro-inflammatory cytokines (TNF-α and IL-6) of LPS-induced macrophages could be downregulated by the CQDs. Besides, the self-healing hydrogel decorated with multifunctional CQDs were prepared via the reaction between OSA and CMCS through Schiff base linkage for better wound management. The CQDs/hydrogel could continuously eliminate bacteria and scavenge ROS to modulate the complex oxidative stress microenvironment. The results of animal experiments demonstrated that the CQDs/hydrogel exerted the effects of eliminating MRSA, anti-inflammation, and promoting angiogenesis, which was manifested in enhancing wound healing, epithelial regeneration and collagen disposition. Therefore, the CQDs/hydrogel is excellent candidate for MRSA-infected skin wound healing. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the epidemiology of Toxoplasma gondii infection in patients with colorectal cancer (CRC) in eastern China. Therefore, 287 primary CRC patients and 287 age-matched healthy control subjects were recruited to estimate the seroprevalence of T. gondii and identify the risk factors of infection. Enzyme-linked immunoassays were used to test for anti-T. gondii immunoglobulin G (IgG) and IgM antibodies. Forty-six (16%) samples were positive for anti-T. gondii IgG antibodies in patients with CRC, compared with 26 (9.1%) in the healthy controls, a significant difference (P = 0.007). By contrast, eight (2.8%) patients tested positive for T. gondii IgM antibodies, compared with three (1.1%) in the controls, a difference that was not significant (P = 0.13). Multivariable backward stepwise logistic regression analysis revealed that a rural residence (OR 2.83; 95% CI 1.15–7.01; P = 0.024) and treatment with chemotherapy (OR 2.16; 95% CI 1.02–4.57; P = 0.045) were risk factors for T. gondii infection in patients with CRC. Thus, T. gondii infection is serious in patients with CRC, and a rural residence and treatment with chemotherapy are independent risk factors for infection by this parasite. Therefore, medical professionals should be aware of this pathogen in patients with CRC, and the causes of T. gondii infection in these patients need to be explored further. [ABSTRACT FROM AUTHOR]

Summary: We reported 20 cases of discharged COVID‐19 patients whose RT‐PCR test results showed 're‐positive'. After finding 're‐positive', these patients were admitted to hospital for the second time and were followed up until the end of May 2020. We recorded detailed treatment and follow‐up process, and collected relevant data. The possible causes and potential clinical significance of this phenomenon are discussed. [ABSTRACT FROM AUTHOR]

Background: Although the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer. Methods: Paired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A. Results: MCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p. Conclusion: MCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the "ceRNA" to regulate the expression of WNT5A by targeting miR-876-5p. [ABSTRACT FROM AUTHOR]