Targeting inhibitor of apoptosis proteins (IAPs) enhances susceptibility of oral squamous carcinoma cells to cisplatin.

PURPOSE: Oral Squamous Cell Carcinoma (OSCC) is the 6th most common cancer worldwide. It is generally aggressive and closely associated with chemoresistance and poor survival. There is accumulating evidence for the involvement of inhibitors of apoptosis proteins (IAPs), including IAP1 and XIAP, in mediating chemotherapy resistance in OSCC. Various strategies for targeting IAPs have been designed and tested in recent years and several small molecule IAP inhibitors are in clinical trials as monotherapies as well as in combination with radiotherapy and chemotherapy. The purpose of this study was to evaluate and compare the efficacy and biological activity of three IAP inhibitors both as stand-alone and sensitising agents to cisplatin in a preclinical model of squamous cell carcinoma of the tongue. METHODS: Cisplatin-sensitive SCC4 and -resistant SCC4cisR cells were utilised in this study. Apoptosis was evaluated by flow cytometric analysis of Annexin V/Propidium Iodide-stained cells. Expression of IAP proteins was determined by western blotting and knockdown of cIAP1, livin and XIAP was conducted by transfection of cells with siRNA. RESULTS: We establish for the first time the therapeutic efficacy of the Smac mimetic, BV6 and the XIAP inhibitor Embelin, for OSCC. Both of these IAP targeting agents synergistically enhanced cisplatin-mediated apoptotic cell death in resistant cells which was mediated in part by depletion of XIAP. In addition, knockdown of XIAP using siRNA enhanced cisplatin-mediated cell death, demonstrating the importance of targeting XIAP in this sensitisation. CONCLUSION: These findings provide pre-clinical evidence that IAP inhibition may be a valuable therapeutic option in OSCC.

Virtual Monoenergetic Images Facilitate Better Identification of the Arc of Riolan During Splenic Flexure Takedown.

OBJECTIVE: This study aimed to investigate whether virtual monoenergetic images (VMIs) can aid radiologists and surgeons in better identifying the arc of Riolan (AOR) and to determine the optimal kilo electron volt (keV) level. METHODS: Thirty-three patients were included. Conventional images (CIs) and VMI (40-100 keV) were reconstructed using arterial phase spectral-based images. The computed tomography (CT) attenuation and noise of the AOR, the CT attenuation of the erector spinal muscle, and the background noise on VMI and CI were measured, respectively. The signal-to-noise ratio, contrast-to-noise ratio (CNR), and signal intensity ratio were calculated. The image quality of the AOR was evaluated according to a 4-point Likert grade. RESULTS: The CT attenuation, noise, CNR, and signal intensity ratio of the AOR were significantly higher in VMI at 40 and 50 keV compared with CI (P < 0.001); VMI at 40 keV was significantly higher than 50 keV (P < 0.05). No significant difference in signal-to-noise ratio, background noise, and CT attenuation of the spinal erector muscle was observed between VMI and CI (P > 0.05). virtual monoenergetic image at 40 keV produced the best subjective scores. CONCLUSIONS: Virtual monoenergetic image at 40 keV makes it easier to observe the AOR with optimized subjective and objective image quality. This may prompt radiologists and surgeons to actively search for it and encourage surgeons to preserve it during splenic flexure takedown.

Clinical application of artificial intelligence-assisted three-dimensional planning in direct anterior approach hip arthroplasty.

PURPOSE: The objective of this study was to investigate the efficacy of an artificial intelligence-assisted 3D planning system (AIHIP) in total hip arthroplasty by direct anterior approach and assess the reliability of the AIHIP preoperative program in terms of both interobserver and intraobserver agreement. METHODS: A retrospective analysis was conducted on patients who underwent unilateral primary THA via direct anterior approach from June 2019 to March 2022. Participants were randomly assigned to receive either the AIHIP system (n = 220) or the 2D template (control group) (n = 220) for preoperative planning. The primary outcome aimed to evaluate the correspondence between the prosthesis selected intro-operation and the one planned preoperatively, as well as to calculate the intraclass correlation coefficient (ICC). Secondary outcomes included operation time, intraoperative blood loss, fluoroscopy times, Harris hip score (HHS), lower limb length difference (LLD), femoral offset (FO), and bilateral femoral offset difference. RESULTS: No significant differences were observed in gender, age, body mass index (BMI), aetiology, and American Society of Anesthesiologists (ASA) score between the two groups. Both planning methods exhibited good intraobserver agreement for component planning (ICC: 0.941-0.976). Interobserver agreement for component planning was comparable between the two methods (ICC: 0.882-0.929). In the AIHIP group, the accuracy of acetabular cup and femoral stem prosthetics planning significantly improved, with accuracies within the size range of ± 0 and ± 1 being 76.8% and 90.5% and 79.5% and 95.5%, respectively. All differences between two groups were statistically significant (p < 0.05). Patients receiving AIHIP preoperative planning experienced shorter operation times, reduced intraoperative blood loss, fewer fluoroscopy times, and lower leg length discrepancy (LLD) (p < 0.05). Moreover, they demonstrated a higher Harris hip score (HHS) at three days post-surgery (p < 0.05). However, no significant differences were found in femoral offset (FO), difference of bilateral femoral offsets, and HHS at 1 month after the operation. CONCLUSION: Utilizing AIHIP for preoperative planning of direct anterior approach THA can significantly enhance the accuracy of prosthetic sizing with good reliability, decrease operation time, reduce intraoperative blood loss, and more effectively restore the length of both lower limbs. This approach has greater clinical application value.

Cation/Anion Codoped and Cobalt-Free Li-Rich Layered Cathode for High-Performance Li-Ion Batteries.

Lithium-rich layered oxides have received great attention due to their high energy density as cathode material. However, the progressive structural transformation from layered to spinel phase triggered by transition-metal migration and the irreversible release of lattice oxygen leads to voltage fade and capacity decay. Here, we report a Fe, Cl codoped and Co-free Li-rich layered cathode with significantly improved structural stability. It is revealed that the Fe and Cl codoping can facilitate the Li-ion diffusion and improve the rate performance of the materials. Moreover, the calculations show that the structural stability is enhanced by Fe and Cl codoping. As a result, the Fe and Cl codopant reduces the irreversible release of lattice oxygen, mitigates voltage fade, and improves the first-cycle Coulombic efficiency. This work provides a low-cost, environmentally friendly, practical strategy for high-performance cathode materials.

Identification and functional analysis of the SARS-COV-2 nucleocapsid protein.

BACKGROUND: A severe form of pneumonia, named coronavirus disease 2019 (COVID-19) by the World Health Organization is widespread on the whole world. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was proved to be the main agent of COVID-19. In the present study, we conducted an in depth analysis of the SARS-COV-2 nucleocapsid to identify potential targets that may allow identification of therapeutic targets. METHODS: The SARS-COV-2 N protein subcellular localization and physicochemical property was analyzed by PSORT II Prediction and ProtParam tool. Then SOPMA tool and swiss-model was applied to analyze the structure of N protein. Next, the biological function was explored by mass spectrometry analysis and flow cytometry. At last, its potential phosphorylation sites were analyzed by NetPhos3.1 Server and PROVEAN PROTEIN. RESULTS: SARS-COV-2 N protein composed of 419 aa, is a 45.6 kDa positively charged unstable hydrophobic protein. It has 91 and 49% similarity to SARS-CoV and MERS-CoV and is predicted to be predominantly a nuclear protein. It mainly contains random coil (55.13%) of which the tertiary structure was further determined with high reliability (95.76%). Cells transfected with SARS-COV-2 N protein usually show a G1/S phase block company with an increased expression of TUBA1C, TUBB6. At last, our analysis of SARS-COV-2 N protein predicted a total number of 12 phosphorylated sites and 9 potential protein kinases which would significantly affect SARS-COV-2 N protein function. CONCLUSION: In this study, we report the physicochemical properties, subcellular localization, and biological function of SARS-COV-2 N protein. The 12 phosphorylated sites and 9 potential protein kinase sites in SARS-COV-2 N protein may serve as promising targets for drug discovery and development for of a recombinant virus vaccine.

Chemical Insights into Antibacterial N-Halamines.

Microbial contamination arising from pathogens poses serious threats to human health and in recent decades has presented an unprecedented challenge to antibacterial research. Of the various antibacterial agents that effectively kill pathogens, halogen-based antibacterial compounds have been successful in eliminating harmful pathogen-associated diseases and are becoming the most popular disinfectants. As a significant subcategory of halogen antibacterial agents, N-halamines have drawn increasing research interest into their chemistry and practical applications. N-Halamines have many advantages over other antibacterial agents, including effectiveness against a broad spectrum of microorganisms, long-term physicochemical stability, high structural durability, and the regenerability of their functional groups, with corresponding renewal of their antibacterial properties. This review examines recent progress and research trends in both theoretical and experimental studies of N-halamines, with the aim of providing a systematic and comprehensive survey and assessment of the significant advances in our understanding of antibacterial N-halamines. This review serves as a practical guide to developing N-halamines through both broad and in-depth basic research and offers suggestions for their potential future applications.

Exosomal lncRNA 91H is associated with poor development in colorectal cancer by modifying HNRNPK expression.

BACKGROUND: Exosomes mediated transfer of lncRNA 91H may play a critical role in the development of CRC. However, few studies have proved the mechanism. So we performed this study to deeply explore the biological functions of exosomal 91H in the development and progression of CRC. METHODS: The association between lncRNA 91H and exosomes was detected in vitro and vivo. Then RNA pulldown and RIP were used to detect how lncRNA 91H affect CRC IGF2 express. At last, clinic pathological significance of exosomal 91H was evaluated by Cox proportional hazards model. RESULTS: We found that serum lncRNA 91H expression was closely related to cancer exosomes in vitro and vivo which may enhance tumor-cell migration and invasion in tumor development by modifying HNRNPK expression. Then the clinic pathological significance of exosomal 91H was evaluated which demonstrated that CRC patients with high lncRNA 91H expression usually showed a higher risk in tumor recurrence and metastasis than patients with low lncRNA 91H expression (P < 0.05). CONCLUSION: All these data suggested that exosomal lncRNA 91H enhancing CRC metastasis by modifying HNRNPK expression might be an early plasma-based biomarker for CRC recurrence or metastasis. Further large-scale studies are needed to confirm our findings.

Long non-coding RNA 91H contributes to the occurrence and progression of esophageal squamous cell carcinoma by inhibiting IGF2 expression.

Long non-coding RNAs (lncRNAs) have been recently recognized as a major class of regulators in mammalian systems. 91H, a novel long noncoding antisense transcripts located on the position of the H19/IGF2 locus has been suggested to play a potential tumor-suppressor role in tumor development. However, little study has proved the mechanism in esophageal squamous cell carcinoma (ESCC). We carried out this study to explore the role of lncRNA 91H in the regulation of H19 imprinting control regions (ICR) and IGF2 expression and the association between 91H and ESCC progression. The cell line TE-1, Eca-109, and 232 ESCC patients' matched sets of paraffin-embedded adjacent normal and tumor samples were obtained in this study. The results showed that 91H expression was significantly lower in patients with higher depth of invasion, neoplastic grading and TNM which usually leads to the overexpression of IGF2 in tumor progression. The expression of 91H usually decreased in TE-1 and Eca-109 when treated with demethylation agent. Further analysis revealed that, in 91H knockdown cell lines, IGF2 expression was also significantly higher than negative controls. Therefore, the results demonstrated that the lncRNA 91H was associated with H19 ICR methylation and inhibited IGF2 expression of ESCC patients which may optimize the mechanism of IGF2 regulation in tumor development. Patients with higher depth of invasion, neoplastic grading and TNM usually demonstrated lower 91H expression potentially represent a novel clinically relevant event to identify individuals at increased risk for the occurrence, progression and prognosis of ESCC.

Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model.

BACKGROUND: Inflammation plays an integral role in carcinogenesis and tumor progression. Inflammatory response biomarkers have shown to be promising prognostic factors for improving the predictive accuracy in various cancers. The aim of this study is to investigate the prognostic significance of pre-operative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in gastric cancer (GC). METHODS: 389 patients who had undergone gastrectomy were enrolled from 2007 to 2009 in this study. NLR, dNLR, PLR and LMR were calculated from peripheral blood cell count taken at pre-operation. Receiver operating curve (ROC) was used to determine the optimal cut-off levels for these biomarkers. A predictive model or nomogram was established to predict prognosis for cancer-specific survival (CSS) and disease-free survival (DFS), and the predictive accuracy of the nomogram was determined by concordance index (c-index). RESULTS: The median follow-up period was 24 months ranging from 3 months to 60 months. The optimal cut-off levels were 2.36 for NLR, 1.85 for dNLR, 132 for PLR and 4.95 for LMR by ROC curves analysis. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), CSS and DFS, however, elevated LMR showed an adverse effect on worse OS, CSS and DFS. Multivariate analysis revealed that elevated dNLR was an independent factor for worse OS, and NLR was superior to dNLR, PLR and LMR in terms of hazard ratio (HR = 1.53, 95% CI = 1.11-2.11, P = 0.010), which was shown to be independent prognostic indicators for both CSS and DFS. Moreover, the nomogram could more accurately predict CSS (c-index: 0.89) and DFS (c-index: 0.84) in surgical GC patients. CONCLUSIONS: Pre-operative NLR and dNLR may serve as potential prognostic biomarkers in patients with GC who underwent surgical resection. The proposed nomograms can be used for the prediction of CSS and DFS in patients with GC who have undergone gastrectomy.

Associations of polymorphisms in microRNAs with female breast cancer risk in Chinese population.

Polymorphisms in microRNA (miRNA) have been discussed to be associated with breast cancer risk; however, the conclusions were always inconsistent in different ethnicities. This case-control study enrolled 450 breast cancer cases, and 450 health controls was carried out to investigate the association between six polymorphisms in miRNAs and breast cancer risk. Sequenom MassARRAY was used to detect the polymorphisms in miRNAs, and the immunohistochemistry assay was applied to detect the expression of estrogen receptor (ER) and progesterone receptor (PR) in cancer tissue. The data showed that the 3746444 GG was associated with increased breast cancer risk (adjusted odds ratio (OR) = 1.71, 95 % confidence interval (CI) = 1.16-2.52) and that rs2292832 CC (adjusted OR = 0.54, 95 % CI = 0.34-0.85) was associated with decreased breast cancer risk. In addition, menopausal status subgroup analysis revealed that rs3746444 GG (adjusted OR = 2.34, 95 % CI = 1.31-4.15) and GA/GG (adjusted OR = 1.60, 95 % CI = 1.08-2.37) genotypes were associated with increased breast cancer risk for the subgroup of women with premenopausal status, respectively. Moreover, rs2910164 GG (adjusted OR = 1.84, 95 % CI = 1.07-3.15) and CG/GG (adjusted OR = 1.47, 95 % CI = 1.01-2.15) genotypes were associated with increased breast cancer risk in the postmenopausal status subcohort, respectively. Furthermore, rs3746444 AG (adjusted OR = 1.61, 95 % CI = 1.06-2.45) and AG/GG (adjusted OR = 1.49, 95 % CI = 1.02-2.18) genotypes were observed to be associated with increased risk of lymph node involvement and breast cancer with negative PR expression, separately. In short, rs3746444 was associated with breast cancer risk, especially for women with premenopausal status, and rs2910164 CG and CG/GG genotypes were associated with breast cancer risk for the women with premenopausal status.

The diplotype Fas -1377A/-670G as a genetic marker to predict a lower risk of breast cancer in Chinese women.

This study was designed to reveal the effects of Fas and FasL polymorphisms of interest on breast cancer risk. A total of 439 patients with breast cancer and 439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas -670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of estrogen receptor, progesterone receptor, and CerbB-2 were determined by immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of breast cancer and adjacent normal tissues were detected by real-time polymerase chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA, Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was associated with the opposite effect. Furthermore, gene-gene interaction analysis revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and -670AA genotypes were associated with higher soluble Fas concentrations than other genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer risk and that Fas polymorphisms are likely to affect breast cancer risk by regulating the soluble Fas concentration.

Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk.

The vitamin D receptor (VDR) can influence cancer susceptibility through binding to vitamin D. However, the previous studies were contradictory. Therefore this meta-analysis was conducted to clarify the association between VDR polymorphisms (BsmI, TaqI, FokI, and ApaI) and cancer risk. One hundred twenty-six studies were enrolled through PubMed. For VDR BsmI polymorphism, significantly increased cancer risks were observed in the overall analysis. In the further stratified analysis, increased risks were observed in colorectal and skin cancer, especially in Caucasian population. However, no significant associations were observed in other VDR polymorphisms in the overall analysis. In the further subgroup analysis, increased risks were found in oral, breast, and basal cell cancer while decreased risk was found in prostate cancer in t allele carriers of TaqI polymorphism. For VDR FokI polymorphism, increased risks were found in ovarian and skin cancer while decreased risk in glioma in f allele carriers. For VDR ApaI polymorphism, increased risk was observed in basal cell cancer, especially in Asian population in a allele carriers. In conclusion, these results indicated that b allele of BamI polymorphism was a risk factor for cancer susceptibility. Meanwhile, t allele of TaqI polymorphism was a risk factor for oral, breast, and basal cell cancer and a protective factor for prostate cancer. Moreover, f allele of FokI polymorphism was a risk factor for ovarian and skin cancer and a protective factor for glioma. Finally, a allele of ApaI polymorphism was a risk factor for basal cell cancer in Asian population.

S-nitrosoproteomics profiling elucidates the regulatory mechanism of S-nitrosylation on beef quality.

This study aimed to quantitively profile the S-nitrosylation in beef semimembranosus (SM) with different treatments (nitric oxide donor or nitric oxide synthase inhibitor) by applying iodoTMT-based nitrosoproteomics. Results showed that 2096 S-nitrosylated cysteine sites in 368 proteins were detected in beef SM. Besides, differential SNO-modified proteins were screened, some of which were involved in crucial biochemical pathways, including calcium-releasing-related proteins, energy metabolic enzymes, myofibrils, and cytoskeletal proteins. GO analysis indicated that differential proteins were localized in a wide range of cellular compartments, such as cytoplasm, organelle, and mitochondrion, providing a prerequisite for S-nitrosylation exerting broad roles in post-mortem muscles. Furthermore, KEGG analysis validated that these proteins participated in the regulation of diverse post-mortem metabolic processes, especially glycolysis. To conclude, changes of S-nitrosylation levels in post-mortem muscles could impact the structure and function of crucial muscle proteins, which lead to different levels of muscle metabolism and ultimately affect beef quality.

Correction: Up-Regulation of 91H Promotes Tumor Metastasis and Predicts Poor Prognosis for Patients with Colorectal Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0103022.].

An electron-blocking interface for garnet-based quasi-solid-state lithium-metal batteries to improve lifespan.

Garnet oxide is one of the most promising solid electrolytes for solid-state lithium metal batteries. However, the traditional interface modification layers cannot completely block electron migrating from the current collector to the interior of the solid-state electrolyte, which promotes the penetration of lithium dendrites. In this work, a highly electron-blocking interlayer composed of potassium fluoride (KF) is deposited on garnet oxide Li6.4La3Zr1.4Ta0.6O12 (LLZTO). After reacting with melted lithium metal, KF in-situ transforms to KF/LiF interlayer, which can block the electron leakage and inhibit lithium dendrite growth. The Li symmetric cells using the interlayer show a long cycle life of ~3000 hours at 0.2 mA cm-2 and over 350 hours at 0.5 mA cm-2 respectively. Moreover, an ionic liquid of LiTFSI in C4mim-TFSI is screened to wet the LLZTO|LiNi0.8Co0.1Mn0.1O2 (NCM) positive electrode interfaces. The Li|KF-LLZTO | NCM cells present a specific capacity of 109.3 mAh g-1, long lifespan of 3500 cycles and capacity retention of 72.5% at 25 °C and 2 C (380 mA g-1) with an average coulombic efficiency of 99.99%. This work provides a simple and integrated strategy on high-performance quasi-solid-state lithium metal batteries.

Inhibition of miR-21 induces biological and behavioral alterations in diffuse large B-cell lymphoma.

MicroRNA-21 (miR-21) has been ascribed a key role in many cellular processes, e.g. tumorigenesis via inhibition of target gene expression. However, its role in diffuse large B-cell lymphoma (DLBCL) is still unclear, and there are no in-depth studies on the relationship between miR-21 and the cellular phenotype of DLBCL. In this study, we investigated the expression and role of miR-21 in the regulation of cell biological processes in DLBCL. Firstly, miR-21 expression was evaluated in three DLBCL cell lines by real-time quantitative reverse-transcription (qRT) polymerase chain reaction (PCR). Then, to determine the possible role of miR-21 in the biological and behavioral characteristics of DLBCL, we performed miR-21 knockdown by transfection with anti-miR-21. In addition, PDCD4 and PTEN were assessed by luciferase reporter assay, qRT-PCR, and Western blot. Our study revealed that miR-21 was significantly upregulated in activated B-cell-like DLBCL cells compared to germinal center-like DLBCL cells. We demonstrated that inhibition of miR-21 induced suppression of proliferation and invasion, as well as increased apoptosis in DLBCL. Moreover, knockdown of miR-21 increased PDCD4 and PTEN expression at the protein level but not at the mRNA level. In conclusion, miR-21 can regulate proliferation, invasion, and apoptosis, and thus it has a potential therapeutic application in DLBCL.

The roles of ADIPOQ genetic variations in cancer risk: evidence from published studies.

Adiponectin produced by adipose tissue, which is involved in complex diseases related to obesity, such as cancer. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. However, epidemiological results were inconsistent. To examine this controversy, we assessed reported studies of association between ADIPOQ polymorphisms and cancer risk. Relevant studies were selected by PUBMED, EMBASE update to January 12th, 2012. According to the acceptance and exclusion criteria, 15 studies involved three polymorphisms (rs266729, rs2241766, rs1501299) of ADIPOQ were included. Summary odds ratio (ORs) and 95 % confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. A total of 15 case-control studies related rs266729 (5,615 cases and 6,425 controls), rs2241766 (5,318 cases and 6,118 controls) and rs1501299 (3,751 cases and 5,104 controls) were included to analyze the ADIPOQ polymorphisms and cancer risk. For rs1501299, T allele was associated with decreased cancer risk. In addition, cancer type subgroup analysis revealed T allele was associated with decreased colorectal and prostate cancer risk. Ethnicity subgroup analysis observed a decreased risk in both Asian and Caucasian descendents. As to rs2241766, a borderline decreased cancer risk was observed. This meta-analysis indicated T allele of rs1501299 was an obvious protection factor for cancer risk, and G allele of rs2241766 was a potential protection factor for cancer risk, especially in Caucasian descendents. Further studies should be performed to clarify the roles of ADIPOQ polymorphisms in the cancer risk.

Snap-through Crack Propagation in Architected Bonded Interfaces Analyzed Using a Mechanoluminescent SAO/E Coating.

We investigate the mechanics of crack propagation in architected adhesive joints whose adherends are inspired to the base plate of the barnacle Amphibalanus (=Balanus) amphitrite, and feature an array of buried hollow cylindrical channels located perpendicularly to the direction of crack growth. Selective laser sintering is used to obtain the adherends that are subsequently bonded in the double cantilever beam configuration to ascertain the mechanics of crack growth. Finite element (FE) simulations are deployed to determine the strain energy release rate (ERR) and to elucidate the salient features of the fracture process. It is shown that the channels induce a modulation of the ERR and enable a crack tip shielding mechanism. Besides, FE simulations based on a cohesive zone approach indicate the occurrence of crack pinning/depinning cycles that are validated via experiments. A highlight of the present study is the use of a mechanoluminescent (ML) coating to unravel the evolution of the transient stress field in the crack tip region. The coating comprises an optical epoxy resin loaded with doped strontium aluminate phosphors (SrAl2O4/Eu2+) and converts mechanical energy into light emission with intensity proportional to the magnitude of mechanical stress. By combining the ML emission patterns with the stress distribution obtained from FEA, we unveil interesting details of snap-through cracking in architected bio-inspired adhesive joints.

Diagnosis of invasive pulmonary fungal infections by a real-time panfungal PCR assay in non-neutropenic patients.

This study explored the utility of quantitative real-time panfungal PCR assay in diagnosing invasive pulmonary fungal diseases (IPFD) in non-neutropenic patients. Panfungal PCR assay was performed on respiratory tract specimens from patients whose clinical signs could not exclude fungal infection. At the same time, the samples were subjected to bacterial and fungal culture, microscopic examination and galactomannan antigen (GM) test in order to find the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 4 diagnostic methods in proven and probable cases. 518 specimens were collected while 63 respiratory tract specimens tested by PCR had positive results. According to diagnostic criteria, 40 patients were diagnosed with IPFD, with 12 proven, 20 probable and 8 possible cases. Among these, 33 patients of PCR results were positive, most of which were from BALF samples (44.12%). 23 cases were caused by Aspergillus species, with Aspergillus fumigatus was the major cause. Other Aspergillus species, including Aspergillus flavus, Aspergillus terreus and Aspergillus nidulans were found in 1 sample respectively. Candida species were found in 5 samples, Pneumocystis jeroveci pneumonia (PJP) in 4 samples and Mucormycosis in 1 sample. An analysis of proven/probable diagnosis showed a sensitivity of 78.13%, specificity of 92.18%, PPV of 39.68% and NPV of 98.46% for PCR and 50%, 85.27%, 35.7%, 95.65% for GM test respectively. The Ct value difference between proven/probable and possible cases had no statistical significance (P = .824). Fungal culture showed a sensitivity of 17.5% while microscopic examination sensitivity of 32.5%. Through stratified analysis, no apparent correlation was found between the Ct value of the PCR assay and GM value (r: 0.223, P = .294). But a conjunction of the 2 tests raised the PPV of Aspergillus to 90%. As shown in this study, the panfungal RT-PCR assay has high sensitivity and consistency with serological test and culture. Its high PPV in the detection of Aspergillus and PJP were also evident.

Fabrication of nitrogen-doped graphene quantum dots based fluorescent probe and its application for simultaneous, sensitive and selective detection of umami amino acids.

In this work, nitrogen-doped graphene quantum dots (N-GQDs) were synthesized by an efficient one-step hydrothermal using hydrated citric acid and urea as the carbon and nitrogen sources, respectively. The fluorescent quantum yield of the N-GQDs was up to 88.20 %, and the fluorescence lifetime was 12.29 ns. Based on the excellent fluorescence property, water-soluble and low cytotoxicity of N-GQDs, a novel fluorescent probe was fabricated and used for simultaneous detection of l-glutamic acid (l-Glu) and l-aspartic acid (l-Asp). Herein, Al3+ was used as a chelant agent for l-Glu shielding. The sensitive response of the probe towards l-Glu and l-Asp presented a wide concentration range with a low detection limit (S/N = 3). The fluorescent probe showed good selectivity, high stability and acceptable reproducibility in the application of l-Glu/l-Asp simultaneous detection in chicken soup. Meanwhile, the detection results of the fluorescent probe were correlated well with those obtained by amino acid analyzer.