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In industry, m‐dinitrobenzene is mainly obtained by two‐step nitration of benzene, but still faces the problem of being heterogeneous and highly exothermic. In this work, a two‐step continuous‐flow nitration was developed in a microreactor, combining benzene nitration and mononitrobenzene nitration in series. The waste acid after the mononitrobenzene nitration stage was utilized in the benzene mononitration stage, and the waste acid in the benzene mononitration stage was treated and concentrated for reuse. The whole process consumes almost no sulfuric acid. Under optimal conditions, the yield of dinitrobenzene was more than 99.0 % and the selectivity of m‐dinitrobenzene was more than 91 % with a residence time of 4 min at 70 °C. In addition, the space‐time yield of the continuous microreactor was 800 times higher than the batch reactor. It provides a safe and efficient method for the industrial production of m‐dinitrobenzene. [ABSTRACT FROM AUTHOR]

TBC1Domain Family Member 25 (TBC1D25) is a protein that contains a TBC/RAB‐GTPase activating protein (GAP) domain, which was shown to participate in autophagy in previous studies. However, the role of TBC1D25 in cerebral ischemia‐reperfusion (I/R) injury remains unknown. In this study, we found that the mRNA and protein expression levels of TBC1D25 decreased in mouse brain after I/R injury and primary cortical neurons treated with oxygen and glucose deprivation/reoxygenation (OGD/R). Then TBC1D25 knockout (KO) mice were applied to demonstrate that TBC1D25 ablation aggravated cerebral I/R‐induced neuronal loss and infarct size. In addition, neuronal apoptosis and inflammation were significantly potentiated in the TBC1D25‐KO group. In in vitro OGD/R model, TBC1D25 knockdown can attenuate neuronal cell viability and aggravate the process of inflammation and apoptosis. Conversely, over‐expression of TBC1D25 in primary neurons ameliorated the aforementioned processes. Mechanistically, RNA‐sequencing (RNA‐seq) analysis revealed mitogen‐activated protein kinase (MAPK) signaling pathway was the most significant pathway that contributed to TBC1D25‐mediated brain I/R injury process. Through experimental verification, TBC1D25 deficiency increased the phosphorylation of the transforming growth factor‐β‐activated kinase 1 (TAK1)‐c‐Jun N‐terminal kinase (JNK)/p38 axis in neurons during the brain I/R injury. Furthermore, we found that TAK1 blockade abrogated the apoptosis and inflammatory response produced by TBC1D25 knockdown in vitro. In conclusion, this study is the first to demonstrate the functional significance of TBC1D25 in the pathophysiology of brain I/R injury, and the protective mechanism of TBC1D25 is dependent on the TAK1‐JNK/p38 pathway. [ABSTRACT FROM AUTHOR]

Background: Determining the status of lymph node (LN) metastasis in rectal cancer patients preoperatively is crucial for the treatment option. However, the diagnostic accuracy of current imaging methods is low. Purpose: To develop and test a model for predicting metastatic LNs of rectal cancer patients based on clinical data and MR images to improve the diagnosis of metastatic LNs. Study type: Retrospective. Subjects: In all, 341 patients with histologically confirmed rectal cancer were divided into one training set (120 cases) and three validation sets (69, 103, 49 cases). Field strength/sequence: 3.0T, axial and sagittal T2‐weighted turbo spin echo and diffusion‐weighted imaging (b = 0 s/mm2, 800 s/mm2) Assessment: In the training dataset, univariate logistic regression was used to identify the clinical factors (age, gender, and tumor markers) and MR data that correlated with LN metastasis. Then we developed a prediction model with these factors by multiple logistic regression analysis. The accuracy of the model was verified using three validation sets and compared with the traditional MRI method. Statistical tests: Univariate and multivariate logistic regression. The area under the curve (AUC) value was used to quantify the diagnostic accuracy of the model. Results: Eight factors (CEA, CA199, ADCmean, mriT stage, mriN stage, CRM, EMVI, and differentiation degree) were significantly associated with LN metastasis in rectal cancer patients (P<0.1). In the training set (120) and the three validation sets (69, 103, 49), the AUC values of the model were much higher than the diagnosis by MR alone (training set, 0.902 vs. 0.580; first validation set, 0.789 vs. 0.743; second validation set, 0.774 vs. 0.573; third validation set, 0.761 vs. 0.524). Data Conclusion: For the diagnosis of metastatic LNs in rectal cancer patients, our proposed logistic regression model, combining clinical and MR data, demonstrated higher diagnostic efficiency than MRI alone. Level of Evidence: 4 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Cetuximab therapy, which heavily relies on the activation of Ras pathway, has been used in KRAS, NRAS, BRAF, and PIK3CA wild‐type colorectal cancer (CRC) (Ras‐normal). However, the response rate only reached 60%, due to false‐negative mutation detection and mutation‐like transcriptome features in wild‐type patients. Herein, by integrating RNA‐seq, microarray, and mutation data, we developed a Ras pathway signature by characterizing KRAS/NRAS/BRAF/PIK3CA mutations to identify the hidden nonresponders from the Ras‐normal patients by mutation detection. Using public and in‐house data of CRC patients treated with cetuximab, discovery of the signature could identify cetuximab‐resistant samples from the Ras‐normal samples. Cetuximab resistance‐related genes, such as PTEN, were significantly and frequently mutated in the identified Ras‐activated samples, whereas two cetuximab sensitivity‐related genes, APC and TP53, showed comutation and significantly higher mutation frequencies in the remaining Ras‐normal samples. Furthermore, all the NF1‐ and BCL2L1‐mutated samples were identified as Ras‐activated from the Ras‐normal samples by the Ras pathway signature with significantly under‐regulated expression. Genes co‐expressed with the two genes were both involved in Ras signaling pathway, the out‐of‐control of which could be attributed by the genes' loss‐of‐function mutations. To improve the treatment of cetuximab in CRC, NF1 and BCL2L1 could be used as complementary detection technique to those applied in clinical. In conclusion, the proposed Ras pathway signature could identify the hidden CRC patients resistant to cetuximab therapy and help to reveal resistance mechanisms. [ABSTRACT FROM AUTHOR]

All‐inorganic zero‐dimensional (0D) metal halides have recently received increasing attention due to their excellent photoluminescence (PL) performance and high stability. Herein, we present the successful doping of copper(I) into 0D Cs2ZnBr4. The incorporating of Cu+ cations enables the originally weakly luminescent Cs2ZnBr4 to exhibit an efficient blue emission centered at around 465 nm, with a high photoluminescence quantum yield (PLQY) of 65.3 %. Detailed spectral characterizations, including ultrafast transient absorption (TA) techniques, were carried out to investigate the effect of Cu+ dopants and the origin of blue emission in Cs2ZnBr4:Cu. To further study the role of the A‐site cation and halogen, A2ZnCl4:Cu (A=Cs, Rb) were also synthesized and found to generate intense sky‐blue emission (PLQY≈73.1 %). This work represents an effective strategy for the development of environmentally friendly, low‐cost and high‐efficiency blue‐emitting 0D all‐inorganic metal halides. [ABSTRACT FROM AUTHOR]

We developed a miniaturized electrochemiluminescence (ECL) instrument coupled with a light‐emitting diode‐based bipolar electrochemical sensor (LED‐BPES). This instrument composes of a microcontroller circuit, a power supply circuit, a potentiostat, an optical detecting circuit, and a communication circuit. The multi‐pixel photon counter (MPPC), which is low‐cost, small‐size, and wide‐range in optical measurements, is chosen as the optical detector. The LED‐BPES composes of a disposable screen‐printed carbon electrode (SPCE) and a surface‐mount red LED. Depended on the closed bipolar electrode (C‐BPE) structure, the LED‐BPES not only avoids the employment of unstable and complex ECL reactions but also offers a cost‐effective alternative for the over‐priced ECL reagents by using a mini‐size commercial LED as the luminescent producer. The combination of MPPC and LED‐BPES helps to set up the simplified and downsized instrument system with low price and high efficiency. The presented instrument coupled with LED‐BPES works excellent in electroactive molecules detection and has great potential in the application of heavy metal ions detection. [ABSTRACT FROM AUTHOR]

FOLFOX (5‐fluorouracil, leucovorin and oxaliplatin) is one of the main chemotherapy regimens for colorectal cancer (CRC), but only half of CRC patients respond to this regimen. Using gene expression profiles of 96 metastatic CRC patients treated with FOLFOX, we first selected gene pairs whose within‐sample relative expression orderings (REO) were significantly associated with the response to FOLFOX using the exact binomial test. Then, from these gene pairs, we applied an optimization procedure to obtain a subset that achieved the largest F‐score in predicting pathological response of CRC to FOLFOX. The REO‐based qualitative transcriptional signature, consisting of five gene pairs, was developed in the training dataset consisting of 96 samples with an F‐score of 0.90. In an independent test dataset consisting of 25 samples with the response information, an F‐score of 0.82 was obtained. In three other independent survival datasets, the predicted responders showed significantly better progression‐free survival than the predicted non‐responders. In addition, the signature showed a better predictive performance than two published FOLFOX signatures across different datasets and is more suitable for CRC patients treated with FOLFOX than 5‐fluorouracil‐based signatures. In conclusion, the REO‐based qualitative transcriptional signature can accurately identify metastatic CRC patients who may benefit from the FOLFOX regimen. [ABSTRACT FROM AUTHOR]

Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non‐CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non‐CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application. [ABSTRACT FROM AUTHOR]

Background: The effect of stress on alcohol consumption in humans is highly variable, and the underlying processes are not yet understood. Attempts to model a positive relationship between stress and increased ethanol (EtOH) consumption in animals have been only modestly successful. Our hypothesis is that individual differences in stress effects on EtOH consumption are mediated by genetics. Methods: We measured alcohol consumption, using the drinking‐in‐the‐dark (DID) paradigm in females from 2 inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), and 35 of their inbred progeny (the BXD family). A control group was maintained in normal housing and a stress group was exposed to chronic mild stress (CMS), consisting of unpredictable stressors over 7 weeks. These included predator, social, and environmental perturbations. Alcohol intake was measured over 16 weeks in both groups during baseline (preceding 5‐week period), CMS (intervening 7‐week period), and post‐CMS (final 4‐week period). Results: We detected a strong effect of CMS on alcohol intake. A few strains demonstrated CMS‐related increased alcohol consumption; however, most showed decreased intake. We identified 1 nearly significant quantitative trait locus on chromosome 5 that contains the neuronal nitric oxide synthase gene (Nos1). The expression of Nos1 is frequently changed following alcohol exposure, and variants in this gene segregating among the BXD population may modulate alcohol intake in response to stress. Conclusions: The results we present here represent the first study to combine chronic stress and alcohol consumption in a genetic reference population of mice. Differences in susceptibility to the effects of stressful environments vis‐à‐vis alcohol use disorders would suggest that the differences have at least some basis in genetic constitution. We have also nominated a likely candidate gene underlying the large individual differences in effects of stress on alcohol consumption. [ABSTRACT FROM AUTHOR]

Background and Aim: Differentially expressed (DE) genes detected at the population‐level through case–control comparison provide no information on the dysregulation frequencies of DE genes in a cancer. In this work, we aimed to identify the genes with universally upregulated or downregulated expressions in colorectal cancer (CRC). Methods: We firstly clarified that DE genes in an individual cancer tissue should be the disease‐relevant genes, which are dysregulated in the cancer tissue in comparison with its own previously normal state. Then, we identified DE genes at the individual level for 2233 CRC samples collected from multiple data sources using the RankComp algorithm. Results: We found 26 genes that were upregulated or downregulated in almost all the 2233 CRC samples and validated the results using 124 CRC tissues with paired adjacent normal tissues. Especially, we found that two genes (AJUBA and EGFL6), upregulated universally in CRC tissues, were extremely lowly expressed in normal colorectal tissues, which were considered to be oncogenes in CRC oncogenesis and development. Oppositely, we found that one gene (LPAR1), downregulated universally in CRC tissues, was silenced in CRC tissues but highly expressed in normal colorectal tissues, which were considered to be tumor suppressor genes in CRC. Functional evidences revealed that these three genes may induce CRC through deregulating pathways for ribosome biogenesis, cell proliferation, and cell cycle. Conclusions: In conclusion, the individual‐level DE genes analysis can help us find genes dysregulated universally in CRC tissues, which may be important diagnostic biomarkers and therapy targets. [ABSTRACT FROM AUTHOR]

Lead‐free zero‐dimensional (0D) organic‐inorganic metal halide perovskites have recently attracted increasing attention for their excellent photoluminescence properties and chemical stability. Here, we report the synthesis and characterization of an air‐stable 0D mixed metal halide perovskite (C8NH12)4Bi0.57Sb0.43Br7⋅H2O, in which individual [BiBr6]3− and [SbBr6]3− octahedral units are completely isolated and surrounded by the large organic cation C8H12N+. Upon photoexcitation, the bulk crystals exhibit ultra‐broadband emission ranging from 400 to 850 nm, which originates from both free excitons and self‐trapped excitons. This is the first example of 0D perovskites with broadband emission spanning the entire visible spectrum. In addition, (C8NH12)4Bi0.57Sb0.43Br7⋅H2O exhibits excellent humidity and light stability. These findings present a new direction towards the design of environmentally‐friendly, high‐performance 0D perovskite light emitters. Fully visible: An air‐stable, zero‐dimensional (0D) organic‐inorganic mixed Bi–Sb halide perovskite (C8H12N)4Bi0.57Sb0.43Br7⋅H2O, in which individual [BiBr6]3− and [SbBr6]3− octahedrons are completely isolated and surrounded by the large organic cation C8H12N+ is reported. This is the first example of 0D perovskites with broadband emission spanning the entire visible spectrum. [ABSTRACT FROM AUTHOR]

5‐Fluorouracil (5‐FU)‐based adjuvant chemotherapy (ACT) is widely used for the treatment of colon cancer. Colon cancers with different primary tumor locations are clinically and molecularly distinct, implied through their response to 5‐FU‐based ACT. In this work, using 69 and 133 samples of patients with stage II‐III right‐sided and left‐sided colon cancer (RCC and LCC) treated with post‐surgery 5‐FU‐based ACT, we preselected gene pairs whose relative expression orderings were significantly correlated with the disease‐free survival of patients by univariate Cox proportional hazards model. Then, from the identified prognostic‐related gene pairs, a forward‐stepwise selection algorithm was formulated to search for an optimal subset of gene pairs that resulted in the highest concordance index, referred to as the gene pair signature (GPS). We identified prognostic signatures, 3‐GPS and 5‐GPS, for predicting response to 5‐FU‐based ACT of patients with RCC and LCC, respectively, which were validated in independent datasets of GSE14333 and GSE72970. With the aid of the signatures, the transcriptional and genomic characteristics between the predicted responders and non‐responders were explored. Notably, both in RCC and LCC, the predicted responders to 5‐FU‐based ACT were characterized by hypermutation, whereas the predicted non‐responders were characterized by frequent copy number alternations. Finally, in comparison with the established relative expression ordering‐based signature, which was developed without considering the differences between RCC and LCC, the newly proposed signatures had a better predictive performance. In conclusion, 3‐GPS or 5‐GPS can robustly predict response to 5‐FU‐based ACT for patients with RCC or LCC, respectively, in an individual level. [ABSTRACT FROM AUTHOR]

Our laboratory previously reported an individual-level signature consisting of nine gene pairs, named 9- GPS. This signature was developed by training on microarray expression data and validated using three independent integrated microarray data sets, with samples of stage I non-small-cell lung cancer after complete surgical resection. In this study, we first validated the cross-platform robustness of 9- GPS by demonstrating that 9- GPS could significantly stratify the overall survival of 213 stage I lung adenocarcinoma ( LUAD) patients detected with RNA-sequencing platform in The Cancer Genome Atlas (TCGA; log-rank P = 0.0318, C-index = 0.55). Applying 9- GPS to all the 423 stage I- IV LUAD samples in TCGA, the predicted high-risk samples were significantly enriched with clinically diagnosed metastatic samples (Fisher's exact test, P = 0.0015). We further modified the voting rule of 9- GPS and found that the modified 9- GPS had a better performance in predicting metastasis states (Fisher's exact test, P < 0.0001). With the aid of the modified 9- GPS for reclassifying the metastasis states of patients with LUAD, the reclassified metastatic samples presented clearer transcriptional and genomic characteristics compared to the reclassified nonmetastatic samples. Finally, regulator network analysis identified TP53 and IRF1 with frequent genomic aberrations in the reclassified metastatic samples, indicating their key roles in driving tumor metastasis. In conclusion, 9- GPS is a robust signature for identifying early-stage LUAD patients with potential occult metastasis. This occult metastasis prediction was associated with clear transcriptional and genomic characteristics as well as the clinical diagnoses. [ABSTRACT FROM AUTHOR]

The reaction of NiCl2 and 3-hydrazine-4-amino-1,2,4-triazole (Hatr) in the mixed solvent of EtOH and H2O yielded a dimer compound ([Ni2(Hatr)2(H2O)2(EtOH)2Cl2]Cl2·EtOH) with water and EtOH molecules coordinated to nickle ions. It crystallized in trigonal space group R-3, a= b=29.67(1) Å, c=8.95(7) Å, β=120(1)°, as determined by single-crystal X-ray diffraction. Then, they were fully characterized by the IR spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TG), and elemental analysis. [ABSTRACT FROM AUTHOR]

Two nitrogen-rich alkali metal salts based on nitrogen-rich anion [Zn(bta)2]2-: {[Na2Zn(bta)2(H2O)8] ·H2O} n ( 1) and {[K2Zn(bta)2(H2O)4]} n ( 2) were synthesized by reactions of alkali hydroxide, N, N-bis(1 H-tetrazol-5-yl)amine (H2bta), and zinc chloride in aqueous solutions. The crystal structures of 1 and 2 were determined by low temperature single-crystal X-ray diffraction and fully characterized by elemental analysis and FT-IR spectroscopy. The structures demonstrate that an infinite 1-dimensional (1D) chain structure is constructed by Na+ ions and bridging water molecules in compound 1, which is connected by extensive hydrogen bonds forming a complex 3D network, whereas compound 2 features a more complicated 3D metal-organic framework (MOF). The thermal behaviors of 1 and 2 were investigated by differential scanning calorimetry (DSC) measurements. The DSC results illustrate that both compounds exhibit high thermal stabilities (decomposition temperature > 345 °C). In addition, the heats of formation were calculated on the basis of the experimental constant-volume energies of combustion measured by using bomb calorimetry. Lastly, the sensitivities towards impact and friction were assessed according to Bundesamt für Materialforschung (BAM) standard methods. [ABSTRACT FROM AUTHOR]

The article discusses results of a study that investigates the crystallization, distribution and comprehensive performance of graphite and high-density polyethylene (HDPE) composites. An overview of the use of four graphites with different particle diameters as HDPE/graphite conductive fillers is given. The study showed that the effect of positive temperature coefficient (PTC) is related to the graphite's particle diameter.