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Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that amyloid proteins, like Abeta (Aβ), are important innate immune effectors in preventing infections. In some previous studies, amyloid peptides have been linked to antimicrobial peptides due to their common mechanisms in membrane-disruption ability, while the other mechanisms of bactericidal protein aggregation and protein function knockdown are less discussed. Besides, another important function of amyloid peptides in pathogen agglutination is rarely illustrated. In this review, we summarized and divided the different roles and mechanisms of amyloid peptides against microbes in antimicrobial activity and microbe agglutination activity. Besides, the range of amyloids' antimicrobial spectrum, the effectiveness of amyloid peptide states (monomers, oligomers, and fibrils), and cytotoxicity are discussed. The good properties of amyloid peptides against microbes might provide implications for the development of novel antimicrobial drug. KEY POINTS: • Antimicrobial and/or microbial agglutination is a characteristic of amyloid peptides. • Various mechanisms of amyloid peptides against microbes are discovered recently. • Amyloid peptides might be developed into novel antimicrobial drugs.

With the increasingly serious problem of environmental pollution and resource scarcity, remanufacturing has become one of the popular research fields to solve these issues. However, the practical information of end-of-life products is different (e.g. type and degree of damage) because of their various operation conditions, which complicates the reprocessing routes. Therefore, a new remanufacturing system scheduling model is proposed in this study that considers not only the coordination of remanufacturing subsystems but also job-shop-type reprocessing shops related to the diversified reprocessing routes. A hybrid meta-heuristic algorithm combining differential evolution algorithm and biogeography-based optimization algorithm through a new representation scheme is presented to address the model efficiently. Furthermore, the basic algorithms are improved by integrating the self-adaptive parameters, efficient migration and mutation operators, local search strategy, and restart strategy. Simulation experiments are performed to demonstrate the effectiveness and practicality of the proposed method compared with four baseline algorithms.

The three-dimensional electronic structure and the nature of Ce 4f electrons of the Kondo insulator CeRu4Sn6 are investigated by angle-resolved photoemission spectroscopy, utilizing tunable photon energies. Our results reveal (i) the three-dimensional k-space nature of the Fermi surface, (ii) the localized-to-itinerant transition of f electrons occurs at a much high temperature than the hybridization gap opening temperature, and (iii) the "relocalization" of itinerant f electrons below 25 K, which could be the precursor to the establishment of magnetic order., 6 pages, 4 figures

Background: Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons’ experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. Methods:This study is designed as a single-centered and randomized controlled trial. Altogether 22 hemifacial microsomia patients are randomly assigned to the experiment group and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height and body length), pain scale and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. Discussion: This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patients outcomes including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. Trial registration: Trial registration: Chinese Clinical Trial Registry: No. ChiCTR2200061565. Registered on June29, 2022.

Elucidation of the mechanisms of T-cell–mediated antitumor responses will provide information for the rational design and development of cancer immunotherapies. Here, we found that calnexin, an endoplasmic reticulum (ER) chaperone protein, is significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells is associated with inhibited T-cell infiltration in tumor tissues and correlates with poor survival of patients with OSCC. We found that calnexin inhibits the proliferation of CD4+ and CD8+ T cells isolated from the whole blood of healthy donors and patients with OSCC and inhibits the secretion of IFNγ, TNFα, and IL2 from these cells. Furthermore, in a melanoma model, knockdown of calnexin enhanced the infiltration and effector functions of T cells in the tumor microenvironment and conferred better control of tumor growth, whereas treatment with a recombinant calnexin protein impaired the infiltration and effector functions of T cells and promoted tumor growth. We also found that calnexin enhanced the expression of PD-1 on CD4+ and CD8+ T cells by restraining the DNA methylation status of a CpG island in the PD-1 promoter. Thus, this work uncovers a mechanism by which T-cell antitumor responses are regulated by calnexin in tumor cells and suggests that calnexin might serve as a potential target for the improvement of antitumor immunotherapy.

Supplementary Data from Porphyromonas gingivalis Promotes Colorectal Carcinoma by Activating the Hematopoietic NLRP3 Inflammasome

Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in colorectal cancer. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted colorectal cancer via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome.Significance:This study demonstrates that the periodontal pathogen P. gingivalis can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment.

Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in colorectal cancer. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted colorectal cancer via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome. Significance: This study demonstrates that the periodontal pathogen P. gingivalis can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment.

Craniosynostosis is one of the most common craniofacial deformities demanding surgical treatment in infancy. LncRNA HOTAIR has verified its important role in osteogenesis and osteoarthritis. However, whether HOTAIR plays an essential role in the development of craniosynostosis is still unclear. In this study, we aimed to investigate the molecular role of HOTAIR in the osteoclast function and development of craniosynostosis.For osteoclast differentiation, RAW264.7 cells were induced by 50 ng/ml of RANKL and 10 ng/mL M-CSF, followed by TRAP staining. Cell proliferation and apoptosis were assayed by the CCK-8 kit and Annexin V-FITC apoptosis detection kit, respectively. The expression of HOTAIR was determined in PBMCs by qRT-PCR. Protein levels of all those involved genes were measured by Western blot assay. A luciferase reporter assay was used to determine the miRNA target validation. The HOTAIR expression in PBMCs from children with craniosynostosis was significantly downregulated. The results of cell proliferation and apoptosis assays indicated that silencing of HOTAIR could inhibit osteoclast differentiation and increase cell apoptosis. Moreover, the luciferase reporter assay revealed that the regulatory axis and HOTAIR-miR-152-CAMKIIα were the regulatory mechanisms of HOTAIR in the osteoclast function and development of craniosynostosis.In this study, our data showed that HOTAIR could promote osteoclast differentiation by binding miR-152. Furthermore, the HOTAIR/HOTAIR-miR-152-CAMKIIα axis was found to regulate osteoclast differentiation. These results indicate that the HOTAIR plays a crucial role in the development of osteoclasts.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8

Background Augmented reality (AR) is a new technology that increases users’ perception of the real world. The purpose of this study is to evaluate the efficacy and safety of augmented reality navigation system in treatment with craniofacial fracture reduction. Methods This will be a single-center prospective randomized controlled trial. Twenty-two patients will be assigned to two groups of 11, and those with zygomaticomaxillary complex fractures will undergo preoperative three-dimensional CT modeling and have operational plans designed. The control team will use traditional optical navigation to perform the surgery, and the experimental team will use an AR navigation system. The primary outcome measures will be the accuracy of the key points of surgical area between the preoperational surgical plan and post-operation. The secondary outcome measures will be the blood loss, operation time, bone reduction time, hospital time, and complication rate. The findings obtained through this study are expected to evaluate efficacy and safety of the augmented reality navigation system in the treatment of zygomaticomaxillary complex fractures. Discussion This controlled trial of augmented reality navigation system in treatment with zygomaticomaxillary complex fracture reduction will clarify the efficacy and safety of this technology by measuring the accuracy of the key points of surgical area and blood loss, operation and bone reduction times, hospital stay duration, and complication rates. This is a single-center study, and the results are expected to promote the application of augmented reality in craniofacial fracture reduction to improve surgery accuracy and efficacy. Trial registration Chinese Clinical Trial Registry ChiCTR1900022626. Registered on April 19, 2019.

Subsequently to the publication of the above article, the authors have found that Fig. 4A on p. 1532 contained some errors. Owing to mistakes made during the preparation and revision of the manuscript, the invasion assay data images selected to show both the 'Control' and 'shRNA2' groups of the invasion and migration experiments were derived from the same original sources. A corrected version of the Fig. 4, showing the correct data for the invasion and migration assay experiments with the Control and shRNA2 groups, is shown below. These inadvertent errors did not affect the conclusions reported in this paper, and all the authors agree with this Corrigendum. The authors thank the editor of Oncology Reports for presenting them with the opportunity to publish this Corrigendum, and apologize to the editor and to the readership of the journal for any inconvenience caused. [the original article was published in Oncology Reports 42: 1527-1538, 2019; DOI: 10.3892/or.2019.7257].

It has been becoming increasingly evident that long non‐coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome‐wide analysis with a lncRNA microarray found that lncRNA HOXA‐AS2 was up‐regulated in HB. Stable transfected cell lines with HOXA‐AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA‐AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up‐regulation of HOXA‐AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA‐AS2 was modulated by chromatin remodelling factor ARID1B and transcription co‐activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA‐AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA‐AS2‐mediated HB carcinogenesis. In conclusion, HOXA‐AS2 is significantly overexpressed in HB and the ARID1B/HOXA‐AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy.

Context Berberine (Ber) can increase the survival rate of septic mice and inhibit inflammation, but whether it has a protective effect on septic cardiomyopathy (SCM) is unclear. Objective To investigate whether Ber ameliorates SCM in a rat model and its potential mechanism. Materials and methods Male SD rats were randomly divided into three groups: control (Con, n = 6) (DD H2O, 2 mL/100 g, ig, qd × 3 d, then saline, 10 mg/kg, ip); sepsis [LPS (lipopolysaccharide), n = 18] (LPS 10 mg/kg instead of saline, ip); and berberine intervention (Ber, n = 18) (Ber, 50 mg/kg instead of DD H2O, ig, qd × 3 d, LPS instead of saline, ip). Hemodynamics, HE staining, ELISA and western blot were performed at 6, 24, and 48 h after intraperitoneal injection of LPS to evaluate the effect of berberine in septic rats. Result Berberine could recover myocardial injury by partially increased ± dp/dt max (1151, 445 mmHg/s) and LVEDP levels (1.49 mmHg) with LPS-induced rats, as well as an ameliorated increase of cTnT (217.53 pg/mL) in the Ber group compared with that in the LPS group (at 24 h). In addition, HE staining results showed that berberine attenuated the myocardial cell swelling induced by LPS. In contrast to the LPS group, the up-regulation of TLR4, p65 TNF-α, and IL-1β were attenuated in the Ber group. Discussion and conclusions Berberine showed a protective effect on septic cardiomyopathy rats possibly through inhibiting the activation of TLR4/NF-κB signalling pathway. Whether it improves SCM through other mechanisms is our ongoing research.

The promise of speech disorders as biomarkers in clinical examination has been identified in a broad spectrum of neurodegenerative diseases. However, to the best of our knowledge, a validated acoustic marker with established discriminative and evaluative properties has not yet been developed for oral tongue cancers. Here we cross‐sectionally collected a screening dataset that included acoustic parameters extracted from 3 sustained vowels /ɑ/, /i/, /u/ and binary perceptual outcomes from 12 consonant‐vowel syllables. We used a support vector machine with linear kernel function within this dataset to identify the formant centralization ratio (FCR) as a dominant predictor of different perceptual outcomes across gender and syllable. The Acoustic analysis, Perceptual evaluation and Quality of Life assessment (APeQoL) was used to validate the FCR in 33 patients with primary resectable oral tongue cancers. Measurements were taken before (pre‐op) and four to six weeks after (post‐op) surgery. The speech handicap index (SHI), a speech‐specific questionnaire, was also administrated at these time points. Pre‐op correlation analysis within the APeQoL revealed overall consistency and a strong correlation between FCR and SHI scores. FCRs also increased significantly with increasing T classification pre‐operatively, especially for women. Longitudinally, the main effects of T classification, the extent of resection, and their interaction effects with time (pre‐op vs. post‐op) on FCRs were all significant. For pre‐operative FCR, after merging the two datasets, a cut‐off value of 0.970 produced an AUC of 0.861 (95% confidence interval: 0.785–0.938) for T3‐4 patients. In sum, this study determined that FCR is an acoustic marker with the potential to detect disease and related speech function in oral tongue cancers. These are preliminary findings that need to be replicated in longitudinal studies and/or larger cohorts., Formant centralization Ratio was primarily approved a sensitive acoustic parameter to imply the general articulation function in patients with oral tongue cancer by support vector machine. Clinical validation in the context of preoperative analysis and longitudinal follow‐up further approved its discriminative and evaluative properties, which need to be reproduced in longitudinal studies with larger cohorts.

Background Conjoined twins are a rare congenital anomaly. If separation of the conjoined organs is feasible, reconstruction of the skin and tissue defects is a challenge for the plastic surgeon. This article describes the use of opposing triangle flaps in the separation of three different kinds of conjoined twins. Methods Plastic surgeons measured each conjoined area and designated the vertical length as a and the width as b. The length of the base of the opposing triangle flap was calculated to match a, and the height of the triangle to match b. Results After detailed calculations and careful surgery, the area of the opposing triangle flaps nearly covered the areas exposed after separation, and the three conjoined twins achieved primary closure of their wounds. The pygopagus and ischiopagus twins recovered uneventfully. The omphalopagus twins developed a wound infection, but after daily wound care, the twins recovered within a week. Conclusions With precise calculations, the opposing triangle flap is a feasible and effective method for defect closure after separation of conjoined twins in certain cases. Clinicians may prefer this technique because it avoids the complications and second surgery necessitated by tissue expanders.

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%, P P = 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498–9.562) and RFS rate (HR = 3.296; 95% CI, 1.279–8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P

Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up- and 571 genes were downregulated, with 32 lncRNAs up- and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

Background/Aims: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. Methods: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. Results: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were “chromosome organization”, “cytoplasm”, and “organic cyclic compound binding”. Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. Conclusions: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

Previous research from our group revealed that the long coding RNA (lncRNA) linc01105 is associated with neuroblastoma proliferation and apoptosis, and that its expression is correlated with the International Neuroblastoma Staging System stage. The purpose of the present study was to investigate the functions of Linc01105 in neuroblastoma. Lentivirus‑mediated linc01105 knockdown was performed in the neuroblastoma cell line SH‑SY5Y. The expression levels of linc01105 and of other associated genes were measured by reverse transcription‑quantitative PCR. Cell Counting Kit‑8 assay and flow cytometry were used to determine cell viability and apoptosis. The levels of proteins were detected using western blot analysis. Bioinformatics analysis and luciferase reporter assays were used to examine the relationship between linc01105, miR‑6769b‑5p and vascular endothelial growth factor A (VEGFA). Angiogenesis ability was measured using a tube formation assay. The results demonstrated that HIF‑1α overexpression promoted the transcription of linc01105 by acting as a transcription factor. Knockdown of linc01105 inhibited neuroblastoma cell proliferation, migration and invasion, and it induced apoptosis. In addition, linc01105 affected the expression of p53 and Bcl‑2 family proteins and activated the caspase signaling pathway. Further functional experiments revealed that linc01105 promoted the expression of the miR‑6769b‑5p target gene VEGFA by acting as a sponge of miR‑6769b‑5p. In conclusion, linc01105 may contribute to neuroblastoma tumorigenesis and development. The present findings indicated that the interplay between the p53/caspase pathway and the linc01105/miR‑6769b‑5p/VEGFA axis may have important roles in the development of neuroblastoma.

Chemodynamic therapy, which produces cytotoxic hydroxyl radicals through intratumoral Fenton reactions, has been extensively explored in nanomedicine for cancer treatment. However, the limited endogenous hydrogen peroxide (H2O2) levels, which serve as the reactant, weakens the anticancer effect of the Fenton reaction. In this work, a cascade catalytically reactive nanosystem has been constructed for the treatment of epithelial and embryonal tumors with high synergetic efficacy through the integration of natural glucose oxidase (GOD) and polyethylene glycol (PEG) onto the surface of Fe3S4 nanoplates (abbreviated as Fe3S4-PEG-GOD NPs). The GOD component consumes glucose in tumor and produces a large amount of H2O2, which provides rich substrates for the Fenton reaction catalyzed by the Fe catalytic center of the nanoplates. The intriguing photothermal conversion efficiency (45%) of the constructed composite nanocatalysts in the second near infrared (NIR-II) biowindow allows for photothermal treatment to substantially strengthen and synergize the anticancer effects of nanocatalysts both in vitro and in vivo. This synergy occurs through generation of a hyperthermic effect necessary for promoting the sequential catalytic reaction. The synergistic anticancer effect has been verified in both epithelial and embryonal tumor mouse models, and provides justification for the biomedical use of multifunctional nanocatalysts for versatile tumor nanotherapeutics.

With the peak in diesel consumption and the impact of new energy in the coming years, research will be focused on the treatment of excess diesel. In addition, low carbon aromatics such as benzene, toluene, and xylene (BTX) are important chemical raw materials that will be in high demand in the next few years but are still in short supply. Thus, many researchers have proposed the use of excess diesel, especially the inferior diesel-like light cycle oil (LCO) to produce BTX. The hydrocracking process is typically used to convert LCO to BTX. To provide some guidance on this topic, this review summarizes the typical group compositions in LCO from different refineries, hydrocracking reaction mechanisms of aromatics and cycloalkanes in LCO, hydrocracking catalysts, improved hydrocracking conditions, related hydrocracking technologies, and future developments in the production of BTX. The amount of aromatics with different ring numbers in LCO has been clearly analyzed, and their part types have also been studied. However, some complex types of aromatics in LCO remain unknown. In addition, the hydrocracking mechanisms and pathways of aromatics in LCO to produce BTX have garnered great attention since the 1990s. Based on this, hydrocracking catalysts and related technologies have been developed by many institutions and corporations to convert aromatics to BTX; however, there are still some problems including an insufficient selectivity of BTX, low yield of liquid products, and excessive energy consumption. In the future, more advanced technologies can be applied to analyze all types of aromatics in LCO, which, along with the aid and application of computational chemistry tools, could help deepen the understanding of the reaction pathways of aromatics and develop more efficient catalysts by balancing the properties of the active phase and supporting the surmounting of current shortcomings. Owing to this high value utilization of inferior diesel, the upcoming problem of diesel surplus can be solved effectively, and the utilization of LCO to produce BTX is one possible path.

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.

Extreme learning machine (ELM), as a new learning mechanism for single hidden layer feedforward neural networks (SLFNs), has shown its good performance, such as fast computation speed and good generalization performance. However, the weak robustness of ELM is an unavoidable defect for image classification tasks. Thus, we propose a novel ensemble method combined rotation forest and selective ensemble model to overcome this problem in this paper. Firstly, ELM and rotation forest are integrated to construct an ensemble classifier (RF-ELM), which combines the advantages of both rotation forest and ELM. The purpose of rotation forest here is to enhance the diversity of each base classifier, thus improving the robustness of classification. Then several ELMs are removed from the ensemble pool by using genetic algorithm (GA) based selective ensemble model to further enhance the generalization performance. Finally, the remaining ELMs are grouped as a selected ensemble classifier (RFSEN-ELM) for image classification. The performance is analysed and compared with several existing methods on benchmark datasets and the experimental results demonstrate that the proposed algorithm substantially improves the accuracy and robustness of classification at an acceptable level of training cost.

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

Purpose: Multiple negative regulators restrict the ability of T cells to attack tumors. This work demonstrates the role of PI3K-interacting protein 1 (Pik3ip1) in restraining T-cell responses and antitumor immunity. Experimental Design: An anti-Pik3ip1 mAb was generated to identify the Pik3ip1 expression pattern of hematopoietic cells. Pik3ip1−/− mice and a Pik3ip1 fusion protein were generated to investigate the effect of Pik3ip1 on T-cell–mediated antitumor immunity in MC38 and B16-F10 tumor models. Immunoblotting and confocal microscopy were used to identify inhibitory effects of Pik3ip1 on T-cell receptor (TCR) signaling. Pik3ip1 expression was quantified, and its impact on T-cell function in human tumors was measured. Results: We demonstrated that Pik3ip1 was predominantly expressed on T cells and served as an essential rheostat for T-cell–mediated immunity. A Pik3ip1 genetic deficiency led to enhanced T-cell responsiveness upon immunization with a neoantigen. Pik3ip1−/− mice exhibited a marked increase in antitumor immunity and were resistant to tumor growth. Furthermore, Pik3ip1 extracellular domain fusion protein enhanced MC38 tumor growth was observed. Mechanistically, we found that Pik3ip1 inhibited TCR signaling by mediating the degradation of SLP76 through Pik3ip1 oligomerization via its extracellular region. Consistent with the results from the mouse models, PIK3IP1 expression correlated with T-cell dysfunction in human tumors. Conclusions: Our data reveal a critical role for Pik3ip1 as a novel inhibitory immune regulator of T-cell responses and provide a potential molecular target for cancer immunotherapy.

This article presents an intelligent algorithm based on extreme learning machine and sequential mutation genetic algorithm to determine the inverse kinematics solutions of a robotic manipulator with six degrees of freedom. This algorithm is developed to minimize the computational time without compromising the accuracy of the end effector. In the proposed algorithm, the preliminary inverse kinematics solution is first computed by extreme learning machine and the solution is then optimized by an improved genetic algorithm based on sequential mutation. Extreme learning machine randomly initializes the weights of the input layer and biases of the hidden layer, which greatly improves the training speed. Unlike classical genetic algorithms, sequential mutation genetic algorithm changes the order of the genetic codes from high to low, which reduces the randomness of mutation operation and improves the local search capability. Consequently, the convergence speed at the end of evolution is improved. The performance of the extreme learning machine and sequential mutation genetic algorithm is also compared with that of a hybrid intelligent algorithm, and the results showed that there is significant reduction in the training time and computational time while the solution accuracy is retained. Based on the experimental results, the proposed extreme learning machine and sequential mutation genetic algorithm can greatly improve the time efficiency while ensuring high accuracy of the end effector.

Potassium (K+) ion is an important biological substance in the human body and plays a critical role in the maintenance of transmembrane potential and hormone secretion. Several detection techniques, including fluorescent, electrochemical, and electrical methods, have been extensively investigated to selectively recognize K+ ions. In this work, a highly sensitive and selective biosensor based on single-layer graphene has been developed for K+ ion detection under Van der Pauw measurement configuration. With pre-immobilization of guanine-rich DNA on the graphene surface, the graphene devices exhibit a very low limit of detection (≈1 nM) with a dynamic range of 1 nM–10 μM and excellent K+ ion specificity against other alkali cations, such as Na+ ions. The origin of K+ ion selectivity can be attributed to the fact that the formation of guanine-quadruplexes from guanine-rich DNA has a strong affinity for capturing K+ ions. The graphene-based biosensors with improved sensing performance for K+ ion recognition can be applied to health monitoring and early disease diagnosis.

Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in "activated" T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

Objective The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.

Caffeine (1, 3, 7-trimethylxanthine) and theobromine (3, 7-dimethylxanthine) are the major purine alkaloids in plants, e.g., tea (Camellia sinensis) and coffee (Coffea arabica). Caffeine is a major component of coffee and is used widely in food and beverage industries. Most of the enzymes involved in the caffeine biosynthetic pathway have been reported previously. Here, we demonstrated the biosynthesis of caffeine (0.38 mg/L) by co-expression of Coffea arabica xanthosine methyltransferase (CaXMT) and Camellia sinensis caffeine synthase (TCS) in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this production platform for making other purine-based alkaloids. To increase the catalytic activity of TCS in an effort to increase theobromine production, we identified four amino acid residues based on structural analyses of 3D-model of TCS. Two TCS1 mutants (Val317Met and Phe217Trp) slightly increased in theobromine accumulation and simultaneously decreased in caffeine production. The application and further optimization of this biosynthetic platform are discussed.