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Autonomous vehicles (AVs) have been made possible by advances in sensing and computing technologies. However, the high cost of AVs makes privatization take longer. Therefore, companies with autonomous vehicles can develop shared autonomous vehicle (SAV) projects. AVs with a high level of automation require high upgrade and use costs. In order to meet the needs of more customers and reduce the investment cost of the company, SAVs with different levels of automation may coexist for a long time. Faced with multiple travel modes (autonomous cars with different levels of automation, private cars, and buses), travelers’ travel mode choices are worth studying. To further differentiate the types of travelers, this paper defines high-income travelers and low-income travelers. The difference between these two types of travelers is whether they have a private car. The differences in time value and willingness to pay of the two types of travelers are considered. Based on the above considerations, this paper establishes a multi-modal selection model with the goal of maximizing the total utility of all travelers and uses the imperial competition algorithm to solve it. The results show that low-income travelers are more likely to choose buses and autonomous vehicles with lower levels of automation, while high-income travelers tend to choose higher levels of automation due to their high value of travel time.

Background: Acute myeloid leukaemia (AML) with t (8;21) or inv (16), called core binding factor (CBF) AML, has a favourable prognosis. However, some CBF-AML patients have persistent measurable residual disease (MRD) and are more likely to relapse after standard chemotherapy treatment. The CAG regimen, composed of cytarabine, aclarubicin and granulocyte colony-stimulating factor, has been proven to be effective and safe in treating refractory AML patients. Method: We performed a retrospective study to evaluate the efficacy of the CAG regimen to eliminate MRD detected by RUNX1::RUNX1T1 and CBFβ::MYH11 transcript levels by quantitative polymerase chain reaction (Q-PCR) among 23 patients. Molecular response was defined as the ratio of fusion transcript after treatment to that before treatment greater than or equal to 0.5. Result: The molecular response rate and median decrease ratio of fusion transcripts at themolecular level of the CAG regimen were 52.5% and 0.53, respectively. Among the 15 patients who had a poor molecular response to the high/intermediate-dose cytarabine regimen, the median decrease ratios of transcripts at the molecular level of high/intermediate-dose cytarabine and CAG were 1.55 and 0.53 (P=0.028), respectively, and 6 of 15 patients achieved amolecular response to CAG (40%). The median disease-free survival was 18 months, and the overall survival rate at three years among all patients was 72.7%±10.7%. The common treatment-related adverse events were nausea (100%), thrombocytopenia (39%) and neutropenia (37.5%). Conclusion: The CAG regimen may have activity in CBF-AML patients and could provide a new option for patients who have a poor molecular response to high/intermediate-dose cytarabine.

Understanding the biological and clinical impact of copy number aberrations (CNAs) on the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring an adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chromosome 1 (chr1q) portend high-risk MM disease, the underpinning molecular etiology remains elusive. Here, with reference to the 3-dimensional (3D) chromatin structure, we integrate multi-omics data sets from patients with MM with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM. Prominent among these genes, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed superenhancers, PBX1 directly regulates critical oncogenic pathways and a FOXM1-dependent transcriptional program. Together, PBX1 and FOXM1 activate a proliferative gene signature that predicts adverse prognosis across multiple types of cancer. Notably, pharmacological disruption of the PBX1-FOXM1 axis with existing agents (thiostrepton) and a novel PBX1 small molecule inhibitor (T417) is selectively toxic against chr1q-amp myeloma and solid tumor cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes, and proposes novel CNA-targeted therapy strategies in MM and other types of cancer.

This review highlights the encouraging advances in hydride transfer-involved dearomatization reaction during the past decade, the content of which is categorized according to the hydride acceptors, namely vinylogous imines and quinone methides.

The reaction of 2-pyridylacetates and α,β-unsaturated pyrazolamides with DBU as the catalyst has been developed. A range of unexplored multisubstituted 2,3-dihydro-4H-quinolizin-4-ones are obtained with satisfactory yields (up to 94%) and excellent diastereoselectivities (all cases >20 : 1 dr) via a dearomative [3 + 3] annulation process. This practical method also features transition metal free, mild reaction conditions, wide functional group tolerance, easy scale-up synthesis, and versatile further derivatization.

ZnO nanorod arrays (NRAs) were fabricated on polyester fabrics (PFs) by a two-step method and modified with Ag by magnetron sputtering. The photogenerated charge transport properties of the Ag/ZnO nanorod heterojunctions were studied by a self-made Kelvin probe system and a surface photovoltage (SPV) test system. The measured work functions (WFs) of the deposited Ag and ZnO nanorod are 4.67 and 5.56 eV, respectively. The SPV spectra indicate that the direction of the inner electric field is from the Ag layer to the inner of the ZnO nanorod. The enhancement of light absorption by the local surface plasma resonance (LSPR) effect of Ag/ZnO NRA was observed by Raman microspectroscopy and UV–vis diffuse reflectance spectroscopy. The photocatalytic activity of the Ag/ZnO NRA-functionalized PFs was evaluated by the photocatalytic degradation of Rhodamine B (RB) solution under visible light. The full photo-oxidation of RB and the outperforming ZnO NRA-coated PFs demonstrate that the enhanced photocatalytic performance of Ag/ZnO NRA-coated PFs results from the cooperation of the inner electric field of the Ag/ZnO nanorod heterojunction and Ag LSPR.

With the wide application of hydraulic servo technology in control systems, the requirement of hydraulic servo position control performance is greater and greater. In order to solve the problems of slow response, poor precision, and weak anti-interference ability in hydraulic servo position controls, a Kalman genetic optimization PID controller is designed. Firstly, aiming at the nonlinear problems such as internal leakage and oil compressibility in the hydraulic servo system, the mathematical model of the hydraulic servo system is established. By analyzing the working characteristics of the servo valve and hydraulic cylinder in the hydraulic servo system, the parameters in the mathematical model are determined. Secondly, a genetic algorithm is used to search the optimal proportional integral differential (PID) controller gain of the hydraulic servo system to realize the accurate control of valve-controlled hydraulic cylinder displacement in the hydraulic servo system. Under the positioning benchmark of step signal and sine wave signal, the PID algorithm and the genetic optimized PID algorithm are compared in the system simulation model established by Simulink. Finally, to solve the amplitude fluctuations caused by the GA optimized PID and reduce the influence of external disturbances, a Kalman filtering algorithm is added to the hydraulic servo system to reduce the amplitude fluctuations and the influence of external disturbances on the system. The simulation results show that the designed Kalman genetic optimization PID controller can be better applied to the position control of the hydraulic servo system. Compared with the traditional PID control algorithm, the PID algorithm optimized by genetic algorithm improves the system’s response speed and control accuracy; the Kalman filter is a good solution for the amplitude fluctuations caused by GA-optimized PID that reduces the influence of external disturbances on the hydraulic servo system.

BackgroundDexmedetomidine has been documented to reduce the dose of both intrathecal local anesthetic during cesarean delivery, and the concentration of ropivacaine needed for inducing analgesia during labor. However, few studies have compared adjuvant dexmedetomidine to fentanyl on how they impact the dose of ropivacaine required during labor. The aim of the current study was to evaluate the efficacy of epidural dexmedetomidine at doses of 0.3, 0.4, or 0.5 and 2 μg/ml of fentanyl (the traditional clinical concentration), when added to epidural 0.125% ropivacaine.MethodsThis was a randomized, double-blinded study that comprised one hundred eighty-eight patients, allocated into four groups receiving either epidural fentanyl at 2 μg/ml, or dexmedetomidine at 0.3, 0.4, or 0.5 μg/ml for labor analgesia. The primary outcome was the amount of ropivacaine necessary per hour. Secondary outcomes included visual analogue pain scale (VAS), motor block (Bromage Scale), side effects, patient satisfaction, and neonatal outcomes.ResultsAt the completion of the study, data from 165 participants were analyzed. The mean hourly amount of epidural ropivacaine administered was 16.2 ± 3.3, 14.0 ± 3.1, 13.1 ± 3.7 and 12.1 ± 2.5 ml/h in the 2 μg/ml fentanyl group, and the 0.3, 0.4 and 0.5 μg/ml dexmedetomidine groups, respectively. There was a significant difference among groups in the mean hourly consumption of epidural ropivacaine (P < 0.0001 for 1 way ANOVA). The frequency of PCEA (patient-controlled epidural analgesia) was significantly higher in the fentanyl group than in the three dexmedetomidine groups (P < 0.001), and similar among the dexmedetomidine groups. The mean values of the VAS among all groups were similar over time, P > 0.05. The incidence of pruritus in the fentanyl group was 17.5%, whereas no patient experienced pruritus in any of the dexmedetomidine groups, P < 0.0001.ConclusionThe study demonstrated that epidural dexmedetomidine (0.3 and 0.4 μg/ml) was superior to standard dose epidural fentanyl in reducing the mean hourly amount of ropivacaine administered, and minimizing opioid-related side effects. Further large and multicenter studies would be necessary to confirm the benefits of dexmedetomidine, and potentially serve as an alternative to opioids for routine use in labor analgesia.Clinical trial registration[http://www.chictr.org.cn/showproj.aspx?proj=62846], identifier [ChiCTR2000039067].

Targeting glutamine catabolism has been attracting more research attention on the development of successful cancer therapy. Catalytic enzymes such as glutaminase (GLS) in glutaminolysis, a series of biochemical reactions by which glutamine is converted to glutamate and then alpha-ketoglutarate, an intermediate of the tricarboxylic acid (TCA) cycle, can be targeted by small molecule inhibitors, some of which are undergoing early phase clinical trials and exhibiting promising safety profiles. However, resistance to glutaminolysis targeting treatments has been observed, necessitating the development of treatments to combat this resistance. One option is to use synergy drug combinations, which improve tumor chemotherapy's effectiveness and diminish drug resistance and side effects. This review will focus on studies involving the glutaminolysis pathway and diverse combination therapies with therapeutic implications.

In this study, p-GaN/AlGaN/GaN high electron mobility transistors (HEMTs) with indium–tin–oxide (ITO) gate electrodes are demonstrated. The DC measurements for the devices show a drain current ( $\text{I}_{\mathrm{ D}}$ ) of 438 mA/mm at a $\text{V}_{\mathrm{ D}}$ and a $\text{V}_{\mathrm{ G}}$ of 10 and 8 V, respectively. A maximum ${g} _{\mathrm{ m}}$ of 92.1 mS/mm and a specific ON-resistance ( $\text{R}_{\mathrm{ on}}\cdot {\mathrm{ A}}$ ) of 1.86 $\text{m}\Omega $ cm2 are obtained. Furthermore, the robustness of the ITO gate electrode atop the p-GaN layer under the forward gate bias is studied, indicating stable $\text{I}_{\mathrm{ G}}-{\mathrm{ V}}_{\mathrm{ G}}$ and $\text{I}_{\mathrm{ D}}-{\mathrm{ V}}_{\mathrm{ G}}$ characteristics for a gate voltage of less than 11 V, which is higher than the compared device with Ni/Au Schottky gate contact. Therefore, ITO gate electrodes, which are compatible with the Light-emitting diode (LED) process, are a promising alternative for p-GaN HEMT technologies.

In this study, p-GaN HEMTs with an indium-tin-oxide (ITO) electrode fabricated on the two different Mg concentration, i.e., $1 \mathbf {\mathrm {\times }} 10 ^{19}$ cm −3 and $8 \mathbf {\mathrm {\times }} 10 ^{19\,\,}$ cm −3,in p-GaN layer are investigated for the first time under the forward gate bias to understand the stability of the forward gate bias breakdown and ${\mathrm {V}}_{TH}$ shift stability. First of all, a Mg concentration in p-GaN layer results in a better Ohmic characteristic between the ITO and p-GaN contact. Furthermore, the fabricated device with a high Mg concentration of p-GaN layer shows a better forward gate breakdown voltage, which can be attributed to the better Ohmic characteristic between p-GaN and ITO electrode. Last, an obvious negative ${\mathrm {V}}_{TH}$ shift is observed, which is most probably related to the hole injections/trapping effects. In sum, the gate breakdown characteristic in p-GaN HEMTs with ITO electrode can be further improved while using high Mg concentration of p-GaN layer while an obvious a negative ${\mathrm {V}}_{TH}$ shift under a forward gate bias is observed, indicating a trade-off between the gate breakdown voltage and ${\mathrm {V}}_{TH}$ instability needs to be carefully considered to optimize the forward gate bias stability in p-GaN HEMTs with an ITO electrode.

In this study, p-GaN HEMTs with an indium-tin-oxide (ITO) electrode fabricated on the two different Mg concentration, i.e., $1 \mathbf {\mathrm {\times }} 10 ^{19}$ cm −3 and $8 \mathbf {\mathrm {\times }} 10 ^{19\,\,}$ cm −3,in p-GaN layer are investigated for the first time under the forward gate bias to understand the stability of the forward gate bias breakdown and ${\mathrm {V}}_{TH}$ shift stability. First of all, a Mg concentration in p-GaN layer results in a better Ohmic characteristic between the ITO and p-GaN contact. Furthermore, the fabricated device with a high Mg concentration of p-GaN layer shows a better forward gate breakdown voltage, which can be attributed to the better Ohmic characteristic between p-GaN and ITO electrode. Last, an obvious negative ${\mathrm {V}}_{TH}$ shift is observed, which is most probably related to the hole injections/trapping effects. In sum, the gate breakdown characteristic in p-GaN HEMTs with ITO electrode can be further improved while using high Mg concentration of p-GaN layer while an obvious a negative ${\mathrm {V}}_{TH}$ shift under a forward gate bias is observed, indicating a trade-off between the gate breakdown voltage and ${\mathrm {V}}_{TH}$ instability needs to be carefully considered to optimize the forward gate bias stability in p-GaN HEMTs with an ITO electrode.

In this study, p-GaN/AlGaN/GaN high electron mobility transistors (HEMTs) with indium–tin–oxide (ITO) gate electrodes are demonstrated. The DC measurements for the devices show a drain current ( $\text{I}_{\mathrm{ D}}$ ) of 438 mA/mm at a $\text{V}_{\mathrm{ D}}$ and a $\text{V}_{\mathrm{ G}}$ of 10 and 8 V, respectively. A maximum ${g} _{\mathrm{ m}}$ of 92.1 mS/mm and a specific ON-resistance ( $\text{R}_{\mathrm{ on}}\cdot {\mathrm{ A}}$ ) of 1.86 $\text{m}\Omega $ cm2 are obtained. Furthermore, the robustness of the ITO gate electrode atop the p-GaN layer under the forward gate bias is studied, indicating stable $\text{I}_{\mathrm{ G}}-{\mathrm{ V}}_{\mathrm{ G}}$ and $\text{I}_{\mathrm{ D}}-{\mathrm{ V}}_{\mathrm{ G}}$ characteristics for a gate voltage of less than 11 V, which is higher than the compared device with Ni/Au Schottky gate contact. Therefore, ITO gate electrodes, which are compatible with the Light-emitting diode (LED) process, are a promising alternative for p-GaN HEMT technologies.

In this study, AlGaN/GaN light-emitting HEMTs (LE-HEMT) with a single quantum well inserted in different locations in the epitaxy layers are fabricated and analyzed. For both structures, light-emitting originated from electrons in the 2DEG and holes from the p-GaN for radiative recombination is located in the quantum well. To investigate the importance of the location of single quantum well, optical characteristics are compared by simulation and experimental results. The experimental results show that the main light-emitting wavelength is shifted from 365 nm in the UV range to 525 nm in the visible range when the radiative recombination is confined in the quantum well and dominates among other mechanisms. Epi B, which has a quantum well above the AlGaN barrier layer in contrast to Epi A which has a quantum well underneath the barrier, shows better intensity and uniformity in light-emitting. According to the simulation results showing the radiative distribution and electron concentrations for both structures, the lower quantum efficiency is due to the diverse current paths in Epi A. On the other hand, Epi B shows better quantum confinement and therefore better luminescence in the same bias condition, which is consistent with experimental observations. These findings are critical for advancing the performance of LE-HEMTs.

Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. Significance: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics.

The process of cancer development and progression is driven by distinct subsets of cancer stem cells (CSCs) that contribute the self-renewal capacity as the major impetus to the metastatic dissemination and main impediments in cancer treatment. Given that CSCs are so scarce in the tumor mass, there are debatable points on the metabolic signatures of CSCs. As opposed to differentiated tumor progenies, CSCs display exquisite patterns of metabolism that, depending on the type of cancer, predominately rely on glycolysis, oxidative metabolism of glutamine, fatty acids, or amino acids for ATP production. Metabolic heterogeneity of CSCs, which attributes to differences in type and microenvironment of tumors, confers CSCs to have the plasticity to cope with the endogenous mitochondrial stress and exogenous microenvironment. In essence, CSCs and normal stem cells are like mirror images of each other in terms of metabolism. To achieve reprogramming, CSCs not only need to upregulate their metabolic engine for self-renewal and defense mechanism, but also expedite the antioxidant defense to sustain the redox homeostasis. In the context of these pathways, this review portrays the connection between the metabolic features of CSCs and cancer stemness. Identification of the metabolic features in conferring resistance to anticancer treatment dictated by CSCs can enhance the opportunity to open up a new therapeutic dimension, which might not only improve the effectiveness of cancer therapies but also annihilate the whole tumor without recurrence. Henceforth, we highlight current findings of potential therapeutic targets for the design of alternative strategies to compromise the growth, drug resistance, and metastasis of CSCs by altering their metabolic phenotypes. Perturbing the versatile skills of CSCs by barricading metabolic signaling might bring about plentiful approaches to discover novel therapeutic targets for clinical application in cancer treatments.Impact statementThis minireview highlights the current evidence on the mechanisms of pivotal metabolic pathways that attribute to cancer stem cells (CSCs) with a special focus on developing metabolic strategies of anticancer treatment that can be exploited in preclinical and clinical settings. Specific metabolic inhibitors that can overwhelm the properties of CSCs may impede tumor recurrence and metastasis, and potentially achieve a permanent cure of cancer patients.

Hexafluoroisopropanol has been demonstrated as the versatile promoter for redox-neutral α-C(sp3)–H functionalization of cyclic amines via the cascade [1,5]-hydride transfer/cyclization strategy. A ...

Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.SignificanceWe provide a comprehensive systems medicine strategy to unveil oncogenic circuitries and inform novel precision therapy decisions against CNA in cancer. This first clinical multi-omic analysis of chr1q-amp in MM identifies a central PBX1-FOXM1 regulatory axis driving high-risk prognosis, as a novel therapeutic target against chr1q-amp in cancer.

Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the effect of phenylephrine on uterine contractions in clinical practice. This study aimed to compare the dose requirement of oxytocin with or without the infusion of prophylactic phenylephrine to prevent post spinal hypotension during cesarean delivery under combined spinal and epidural anesthesia.Methods: This was a double-blinded, single-center, randomized, control study. One hundred and sixty pregnant patients provided informed consent and were randomly allocated to the phenylephrine (phenylephrine infusion) and control (saline infusion) groups. Patients randomized to the phenylephrine group received an intravenous prophylactic phenylephrine infusion at a fixed rate of 0.5 μg/kg/min. The control group received a saline placebo at the same rate and used the same apparatus for delivery. After neonatal delivery and clamping of the umbilical cord, patients received a standard institutional oxytocin protocol. The primary outcome measure was the total dose of oxytocin administered during CD. Secondary outcomes including the proportion (%) of patients requiring a secondary uterotonic agent and estimated blood loss (EBL) in the first 24 h after surgery.Results: The median oxytocin dose administered was significantly higher in the phenylephrine group than in the control group [6.9 ± 2.5 international standardized units (IU) vs. 5.4 ± 2.4 IU, p = 0.0004]. The number of patients that required a secondary uterotonic agent was significantly higher in the phenylephrine group than in the control group (24.2% vs. 9.1%; p = 0.034). The EBL in the first 24-h postoperatively was similar between the two groups (467 ± 47 ml vs. 392 ± 38 ml; p = 0.22).Conclusions: Prophylactic infusion of phenylephrine used to prevent post-spinal hypotension during CD was associated with a higher dose of oxytocin. This has important clinical implications, as the suboptimal use of oxytocin is associated with an increased risk of postpartum hemorrhage and increased maternal morbidity and mortality. Further studies are now needed to confirm these findings.

The line field (LF) design choice for the lateral image formation mechanism (lateral format) has historically been a fraction of the whole optical coherence tomography (OCT) field. However, as the OCT technology develops, the parallelised acquisition of LF-OCT formats (LF-time domain (TD)-OCT, LF-spectral domain (SD)-OCT, LF-swept source (SS)-OCT) offers benefits and capabilities, which may mean it is now becoming more mainstream. Prior reviews on OCT have focused on scanning point (SP) and, to a lesser extent, full field (FF), lateral formats, with, to our knowledge, no prior review specifically on the LF lateral format. Here, we address this gap in the literature by reviewing the history of each LF-OCT format, identifying the applications it has had and providing generic system design overviews. We then provide an analysis and discussion of the benefits and drawbacks of the format.

Cancer stem cells (CSCs) are heterogeneous cells with stem cell-like properties that are responsible for therapeutic resistance, recurrence, and metastasis, and are the major cause for cancer treatment failure. Since CSCs have distinct metabolic characteristics that plays an important role in cancer development and progression, targeting metabolic pathways of CSCs appears to be a promising therapeutic approach for cancer treatment. Here we classify and discuss the unique metabolisms that CSCs rely on for energy production and survival, including mitochondrial respiration, glycolysis, glutaminolysis, and fatty acid metabolism. Because of metabolic plasticity, CSCs can switch between these metabolisms to acquire energy for tumor progression in different microenvironments compare to the rest of tumor bulk. Thus, we highlight the specific conditions and factors that promote or suppress CSCs properties to portray distinct metabolic phenotypes that attribute to CSCs in common cancers. Identification and characterization of the features in these metabolisms can offer new anticancer opportunities and improve the prognosis of cancer. However, the therapeutic window of metabolic inhibitors used alone or in combination may be rather narrow due to cytotoxicity to normal cells. In this review, we present current findings of potential targets in these four metabolic pathways for the development of more effective and alternative strategies to eradicate CSCs and treat cancer more effectively in the future.

The purpose of this study was to assess the accuracy, repeatability, and performance limits of in vivo Mirau ultrahigh axial resolution (UHR) line field spectral domain (LF-SD) optical coherence tomography (OCT) for the measurement of Bowman's and epithelial thickness, and to provide a reference range of these values for healthy corneas.Volunteers with no history and evidence of corneal disease were included in this study. An in vivo graph search image segmentation of the central cornea was obtained at the normal interface vector orientation. The Mirau-UHR-LF-SD-OCT system used has an axial resolution down to 2.4 µm in air (1.7 µm in tissue), with an A-scan speed of 204.8 kHz and a signal to noise ratio (sensitivity) of 69 (83) dB.Nine volunteers were included, one of whom wore contact lenses. The repeatability of mean Bowman's and epithelial thicknesses were 0.3 and 1.0 µm, respectively. The measured 95% population range for healthy in vivo thickness was 13.7 to 19.6 µm for the Bowman's layer, and 41.9 to 61.8 µm for the epithelial layer.The measured thicknesses of Bowman's layer and the corneal epithelium using the Mirau-UHR-LF-SD-OCT were both accurate, with the range for healthy in vivo thicknesses matching prior confocal and OCT systems of varying axial resolutions, and repeatable, equaling the best value prior reported.T1. Development of a commercially viable clinical UHR OCT technology, enabling accurate measurement and interpretation of Bowman's and epithelial layer thickness in clinical practice.

Summary PBX1 is a transcription factor involved in diverse cellular functions including organ development, stem cell renewal, and tumorigenesis. PBX1 is localized at chr1q23.3, a frequently amplified chromosomal region, and it is overexpressed in many human malignancies. Cancer cells with elevated PBX1 signaling are particularly vulnerable to PBX1 withdrawal. We designed a series of small molecule compounds capable of docking to the interface between PBX1 and its cognate DNA target sequence. Among them, T417 is found to be a lead compound. In cell-based assays, T417 significantly suppressed self-renewal and proliferation of cancer cells expressing high levels of PBX1. T417 also re-sensitized platinum-resistant ovarian tumors to carboplatin. T417 did not affect healthy tissues likely due to their lower PBX1 expression levels. Therefore, targeting PBX-DNA interface can be a promising strategy for treating human tumors reliant on PBX1 for survival., Graphical abstract, Highlights • Developing small molecular compounds to interfere with PBX1 protein and DNA interaction • Lead compound, T417, is potent in affecting PBX1 transcription • T417 displays low in vivo toxicity and satisfactory in vivo anti-tumor potency, Chemistry; Cancer

SUMMARY N-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. In this study, we show a specific role of NAAG in cancer. We found that NAAG is more abundant in higher grade cancers and is a source of glutamate in cancers expressing glutamate carboxypeptidase II (GCPII), the enzyme that hydrolyzes NAAG to glutamate and N-acetyl-aspartate (NAA). Knocking down GCPII expression through genetic alteration or pharmacological inhibition of GCPII results in a reduction of both glutamate concentrations and cancer growth. Moreover, targeting GCPII in combination with glutaminase inhibition accentuates these effects. These findings suggest that NAAG serves as an important reservoir to provide glutamate to cancer cells through GCPII when glutamate production from other sources is limited. Thus, GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition., In Brief Nguyen et al. show that NAAG is more abundant in higher grade cancers and a source of glutamate in cancers expressing GCPII, the enzyme that hydrolyzes NAAG to glutamate and NAA. The results suggest that GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition., Graphical Abstract

The oxindole-embedded ortho-quinone methides were employed as reactive intermediates in formal [4 + 2] annulation with 1,3-dicarbonyls, providing an efficient access to spiro[chromen-4,3'-oxindole] scaffolds via a cascade conjugate addition/ketalization/dehydration process. This protocol featured metal-free conditions, wide substrate scope, and excellent yields.

Crop residue burning is the major biomass burning activity in China, strongly influencing the regional air quality and climate. As the cultivation pattern in China is rather scattered and intricate, it is a challenge to derive an accurate emission inventory for crop residue burning. In this study, we proposed a remote sensing-based method to estimate nitrogen oxide (NOx) emissions related to crop residue burning at the field level over Hubei, China. The new method considers differences in emission factors and the spatial distribution for different crop types. Fire radiative power (FRP) derived from moderate-resolution imaging spectroradiometer (MODIS) was used to quantify NOx emissions related to agricultural biomass combustion. The spatial distribution of different crops classified by multisource remote sensing data was used as an a priori constraint. We derived a new NOx emission database for Hubei from 2014 to 2016 with spatial resolution of 1 × 1 km. Significant seasonal patterns were observed from the NOx emission database. Peak NOx emission occurring in October was related to the residue burning in late autumn harvesting. Another peak was observed between January and April, which was due to the frequent burning of stubble before spring sowing. Our results were validated by comparing our emission inventory with geostationary satellite observations, previous studies, global fire emission database (GFED), NO2 vertical column densities (VCDs) from ozone monitoring instrument (OMI) satellite observations, and measurements from environmental monitoring stations. The comparisons showed NOx emission from GFED database was 47% lower than ours, while the evaluations from most of the statistical studies were significantly higher than our results. The discrepancies were likely related to the differences of methodology and data sources. The spatiotemporal variations of NOx emission in this study showed strong correlations with NO2 VCDs, which agreed well with geostationary satellite observations. A reasonable correlation between in situ NO2 observations and our results in agricultural regions demonstrated that our method is reliable. We believe that the new NOx emission database for crop residue burning derived in this study can potentially improve the understanding of pollution sources and can provide additional information for the design of pollution control measures.

Hexafluoroisopropanol has been demonstrated as the versatile promoter for redox-neutral α-C(sp

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The differentiations in nitrogen-converting activity and microbial community structure between granular size fractions in a continuous completely autotrophic nitrogen removal over nitrite (CANON) reactor, having a superior specific nitrogen removal rate of 0.24 g/(g VSS·d), were investigated by batch tests and high-throughput pyrosequencing analysis, respectively. Results revealed that a high dissolved oxygen concentration (>1.8 mg/l) could result in efficient nitrite accumulation with small granules (0.2-0.6 mm in diameter), because aerobic ammonium-oxidizing bacteria (genus Nitrosomonas) predominated therein. Meanwhile, intermediate size granules (1.4-2.0 mm in diameter) showed the highest nitrogen removal activity of 40.4 mg/(g VSS·h) under sufficient oxygen supply, corresponding to the relative abundance ratio of aerobic to anaerobic ammonium-oxidizing bacteria (genus Candidatus Kuenenia) of 5.7. Additionally, a dual substrate competition for oxygen and nitrite would be considered as the main mechanism for repression of nitrite-oxidizing bacteria, and the few Nitrospira spp. did not remarkably affect the overall performance of the reactor. Because all the granular size fractions could accomplish the CANON process independently under oxygen limiting conditions, maintaining a diversity of granular size would facilitate the stability of the suspended growth CANON system.

In this study, a high-rate CANON (Complete Autotrophic Nitrogen-removal Over Nitrite) process was started up successfully by enhancing the in-situ enrichment of anammox bacteria in aerobic granules at conditions relevant for mainstream wastewater treatment. Firstly, to provide nitrite for anammox bacteria growth efficient nitrite-oxidizing bacteria (NOB) repression was rapidly achieved and stably maintained. Both low dissolved oxygen (DO) and ammonium concentrations ratio (DO/NH4+