A 640 nA IQ Output-Capacitor-Less Low Dropout (LDO) Regulator with Sub-Threshold Slew-Rate Enhancement for Narrow Band Internet of Things (NB-IoT) Applications.

An ultra-low quiescent current output-capacitor-less low dropout (OCL-LDO) regulator for power-sensitive applications is proposed in this paper. To improve the gain of the OCL-LDO feedback loop, the error amplifier employs a combination of a cross-coupled input stage for boosting the equivalent input transconductance and a negative resistance technique to improve the gain. Meanwhile, in order to address the issue of transient response of the ultra-low quiescent current OCL-LDO, a sub-threshold slew-rate enhancement circuit is proposed in this paper, which consists of a transient signal input stage and a slew-rate current increase branch. The proposed OCL-LDO is fabricated in a 0.18 µm CMOS process with an effective area of 0.049 mm2. According to the measurement results, the proposed OCL-LDO has a maximum load current of 100 mA and a minimum quiescent current of 640 nA at an input voltage of 1.2 V and an output voltage of 1 V. The overshoot and undershoot voltages are 197 mV and 201 mV, respectively, and the PSR of the OCL-LDO is -72.4 dB at 1 kHz when the load current is 100 µA. In addition, the OCL-LDO has a load regulation of 7.6 µV/mA and a line regulation of 0.87 mV/V.

First-line immune checkpoint inhibitors in low programmed death-ligand 1-expressing population.

Introduction: Inhibitors of programmed cell death 1 (PD1) and its ligand (PDL1) have exhibited favorable long-term survival in many types of advanced-stage cancer and current approvals have to date been granted in certain tumour types irrespective of PD-L1 status. Methods: We extracted the following information: study sample size, trial period, cancer types, intervention of treatment, type of PD-L1 antibody, immunohistochemistry (IHC) scoring method, number and percentage of PD-L1 < 1% population, and median follow- up time. PD-L1 expression was defined as percentage of number of PD-L1-stained tumor cells (TPS), area of tumor infiltrated by PD-L1-stained immune cells (IPS), number of PD-L1-stained cells (tumor cells, lymphocytes and macrophages; CPS). Different trials used distinct method to define low PD-L1 expression. The risk of bias of the included trials was assessed by using the Cochrane risk of bias tool for RCTs. Results: Here, a total of 34 trials were included to extract individual patient data (IPD) to evaluate the survival benefit of first line PD1/PDL1 inhibitors vs. standard-of-care (SOC) in patients with PDL1 < 1%. In term of anti-PD-1/PD-L1 monotherapy, OS (HR = 0.90, 0.81-1.01) and PFS (HR = 1.11, 0.97-1.27) between PD-1/PD-L1 inhibitor group and SOC group were comparable. In term of anti-PD-1/PD-L1 combination therapy, PD-1/PD-L1 inhibitor group exhibited longer OS (median 19.5 months vs. 16.3 months; HR = 0.83, 0.79-0.88, p < 0.001) and PFS than those of SOC group (median 8.11 months vs. 6.96 months; HR = 0.82, 0.77-0.87, p < 0.001).Subgroup analysis showed that survival benefit was mainly observed in non-small cell lung cancer (NSCLC) (HROS = 0.74; HRPFS = 0.69; p < 0.001), small-cell lung cancer (SCLC) (HROS = 0.58, p < 0.001; HRPFS = 0.55, p = 0.030), esophageal squamous cell carcinoma (ESCC) (HROS = 0.62, p = 0.005; HRPFS = 0.79, p < 0.001), melanoma (HROS = 0.53, p < 0.001) and nasopharyngeal carcinoma (NPC) (HRPFS = 0.35, p = 0.013). Conclusion: Anti-PD-1/PD-L1 combinational therapy rather than monotherapy exhibit survival benefit in the low PD-L1 population in the first-line setting, and the survival benefit was mainly observed in specific tumor types.

Analyzing the factors influencing speeding behavior based on quasi-induced exposure and random parameter logit model with heterogeneity in means.

INTRODUCTION: Speeding behavior is a major threat to road traffic safety, which can increase crash risks and result in severe injury outcomes. Although several studies have been conducted to analyze speeding crashes and relevant influential factors, the heterogeneity of variables has not been fully explored. Based on the traffic crash data extracted from the Crash Report Sampling System, the study aims to identify the factors that influence speeding driving with the consideration of variable heterogeneity. METHOD: Quasi-induced exposure technique is adopted to identify the disparities in the propensities of speeding for various driving cohorts. The random parameter logit model with heterogeneity in means is employed to examine the factors impacting speeding behavior. RESULTS: Results indicate that: (a) driving cohorts such as young drivers, male drivers, passenger cars, and pickups appear to have higher propensities of engaging in speeding driving; (b) the propensity of speeding is higher when the driver is drinking, distracted, changing lanes, negotiating a curve, driving in lighted condition, and on curved roads; and (c) the random parameter logit model with heterogeneity in means has better performance as opposed to that without heterogeneity in means. CONCLUSIONS: Speeding behavior can be influenced by various factors in terms of driver-vehicle characteristics, physical condition, driving actions, and environmental conditions. PRACTICAL APPLICATIONS: The findings could serve to develop effective countermeasures to reduce speeding behavior and improve traffic safety.

Method and system design for spectral imaging based on dual micro-lens array field-of-view segmentation.

The function of a mask in the integral field imaging spectrometer (IFIS), which segments image and samples, leads to the drawback of low spectral energy transmittance. Here, we improve field-of-view segmentation method and propose a dual micro-lens array imaging spectrometer (DMAIS). DMAIS comprises a projection lens (PL), a segmentation collimation module (SCM), and a telecentric lens (TL). And SCM, based on a dual micro-lens array, is the core component of it. By employing a lens array focusing approach instead of aperture sampling, DMAIS effectively enhances energy transmittance and reduces spectral bending. The ZEMAX simulation results indicate that compared to IFIS, DMAIS demonstrates a 109.2% increase in energy transmittance and a 32.9% reduction in spectral bending.

lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

A lexicon-based diachronic comparison of emotions and sentiments in literary translation: A case study of five Chinese versions of David Copperfield.

In the Chinese context, translations have served as a useful conduit for providing access to wider literature authored in other languages. A prominent question has been whether translators' linguistic choices are influenced by factors such as translators' social and cultural background and emotions towards the texts they are translating. When multiple translations of the same text over a span of time are produced, another layer of complexity is introduced, and research such as the present study, must examine how or whether variation in the expression of emotions within translations produced over a period of time is discernible. To this end, the present study made use of Lexicon-based Sentiment Analysis (LBSA), a common natural language processing (NLP) approach, to study people's attitudes, opinions or emotions towards a certain person or thing. LBSA has attracted much attention in the literary works or translated works for analyzing reader response and appraisal of the works themselves. The present study undertook a diachronic comparison of emotions and sentiments in five translations of David Copperfield based on the emotion lexicons. The corpus of the study comprised translations of five books and 3,084,599 tokens. We applied the computational method of emotion and sentiment analysis to the emotion words in the five translations. In addition, we used python and R package to analyze the positive and negative words in five versions. The study revealed that translators as social beings in the target world express unique reactions towards the same emotion in the original text as well as in literary translations. Yet, the modern vernacular Chinese versions also showcase a similarity in the expression of emotions thus demonstrating the decisive role of the overall flow of emotion in the original plays and in translation. The contribution of the study is significant as it is a pioneering investigation given that it undertakes a sentiment and emotion analysis of literary translations in Chinese.

STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.

SPINK4 promotes colorectal cancer cell proliferation and inhibits ferroptosis.

BACKGROUND: Little is known about the role of serine peptidase inhibitor Kazal type 4 (SPINK4) in colorectal cancer (CRC) and ferroptosis. Therefore, this study aimed to determine the effect of SPINK4 on CRC pathogenesis and ferroptosis. METHODS: SPINK4 expression was analyzed in public datasets and examined using immunohistochemistry. The biological function of SPINK4 in CRC cell lines and its effect on ferroptosis were tested. An immunofluorescence assay was performed to determine the location of SPINK4 in cells, and mouse models were established to determine the effects of SPINK4 in vivo. RESULTS: CRC datasets and clinical samples analysis revealed that SPINK4 mRNA and protein levels were significantly reduced in CRC tissues compared to control tissues (P < 0.05). Two CRC cell lines (HCT116 and LoVo) were selected, and the in vitro and in vivo experiments showed that overexpression of SPINK4 greatly promotes the proliferation and metastasis of CRC cells and tumor growth (P < 0.05). The immunofluorescence assay indicated that SPINK4 is mainly located in the nucleoplasm and nucleus of CRC cells. Furthermore, SPINK4 expression was reduced after cell ferroptosis induced by Erastin, and overexpression of SPINK4 greatly inhibited ferroptosis in CRC cells. The results of mouse model further demonstrated that SPINK4 overexpression inhibited CRC cell ferroptosis and facilitated tumor growth. CONCLUSIONS: SPINK4 was decreased in CRC tissues and promoted cell proliferation and metastasis; overexpression of SPINK4 inhibited CRC cell ferroptosis.

Retrospect and prospect of aerobic biodegradation of aniline: Overcome existing bottlenecks and follow future trends.

Aniline is a highly bio-toxic industrial product, even at low concentrations, whose related wastewater has been flowing out worldwide on a large scale along with human production. As a green technology, aerobic biological treatment has been widely applied in industrial wastewater and exhibited various characteristics in the field of aniline wastewater. Meanwhile, this technology has shown its potential of synchronous nitrogen removal, but it still consumes energy badly. In the face of resource scarcity, this review comprehensively discusses the existing research in aerobic biodegradation of aniline wastewater to find out the developmental dawn of aerobic biological treatment. Primarily, it put forward the evolution history details of aniline biodegradation from pure culture to mixed culture and then to simultaneous nitrogen removal. On this basis, it presented the existing challenges to further expand the application of aerobic biotechnology, including the confusions of aniline metabolic mechanism, the development of co-degradation of multiple pollutants and the lack of practical experience of bioreactor operation for aniline and nitrogen removal. Additionally, the prospects of the technological shift to meet the needs of an energy-conserving society was described according to existing experiences and feasibility. Including but not limiting to the development of multifunctional bacteria, the reduction of greenhouse gases and the combination of green technologies.

Distributed Neural-Network-Based Cooperation Control for Teleoperation of Multiple Mobile Manipulators Under Round-Robin Protocol.

This article addresses the distributed cooperative control design for a class of sampled-data teleoperation systems with multiple slave mobile manipulators grasping an object in the presence of communication bandwidth limitation and time delays. Discrete-time information transmission with time-varying delays is assumed, and the Round-Robin (RR) scheduling protocol is used to regulate the data transmission from the multiple slaves to the master. The control task is to guarantee the task-space position synchronization between the master and the grasped object with the mobile bases in a fixed formation. A fully distributed control strategy including neural-network-based task-space synchronization controllers and neural-network-based null-space formation controllers is proposed, where the radial basis function (RBF) neural networks with adaptive estimation of approximation errors are used to compensate the dynamical uncertainties. The stability and the synchronization/formation features of the single-master-multiple-slaves (SMMS) teleoperation system are analyzed, and the relationship among the control parameters, the upper bound of the time delays, and the maximum allowable sampling interval is established. Experiments are implemented to validate the effectiveness of the proposed control algorithm.

Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity.

The clinical application of cisplatin is limited by its adverse events, of which nephrotoxicity is the most commonly observed. In a cisplatin-induced pathological response, oxidative stress is one of the upstream reactions which inflicts different degrees of damages to the intracellular material components. Reactive oxygen species (ROS) are also one of the early signaling molecules that subsequently undergo a series of pathological reactions, such as apoptosis and necrosis. This review summarizes the mechanism of intracellular ROS generation induced by cisplatin, mainly from the consumption of endogenous antioxidants, destruction of antioxidant enzymes, induction of mitochondrial crosstalk between the endoplasmic reticulum by ROS and Ca2+, and destruction of the cytochrome P450 (CYP) system in the endoplasmic reticulum, all of which result in excessive accumulation of intracellular ROS and oxidative stress. In addition, studies demonstrated that natural antioxidants can protect against the cisplatin-induced nephrotoxicity, by reducing or even eliminating excess free radicals and also affecting other nonredox pathways. Therefore, this review on the one hand provides theoretical support for the research and clinical application of natural antioxidants and on the other hand provides a new entry point for the detailed mechanism of cisplatin nephrotoxicity, which may lay a solid foundation for the future clinical use of cisplatin.

Fabrication of lanthanum/chitosan co-modified bentonite and phosphorus removal mechanism from low-concentration landscape water.

It is essential to solve the problem of phosphorus pollution in urban landscape water and reduce the degree of eutrophication. In this paper, lanthanum-modified bentonite (La-B) was prepared by high-temperature calcination and liquid-phase precipitation. Then La-B was modified with chitosan to prepare a low-cost environment-friendly functional material: lanthanum/chitosan co-modified bentonite (La-BC). It can reach the adsorption equilibrium within 30 min, and the maximum adsorption capacity is 15.5 mg/g (initial phosphate concentration 50 mg/L); when the target concentration is 2 mg/L, the removal rate can reach 98.5%. La-BC has a stronger anti-interference ability to common coexisting anions SO42-, HCO3-, NO3- and Cl- in the urban landscape water body. La-BC has excellent performance in weakly acidic to neutral water, and its pH applicable range has been improved, making it possible to apply in practical water. The fitting results show that the adsorption behavior conforms to the pseudo-second-order kinetic model and the Freundlich model. After 5 regenerations, the removal efficiency remained around 80%. In the actual water test results, the phosphate concentration can be controlled below 0.1 mg/L and the removal rate is above 75%. Due to its low cost and reusability, it has great potential in the practical application of phosphate removal from landscape water.

Construction and Validation of an Oxaliplatin-Resistant Gene Signature in Colorectal Cancer Patients Who Underwent Chemotherapy.

Aberrant expression of genes contributes to the chemoresistance of colorectal cancer (CRC) treatment. This study aimed to identify genes associated with the chemoresistance of oxaliplatin-based chemotherapy in CRC patients and to construct a signature. Oxaliplatin resistance-related genes were screened by analyzing the gene profiles of cell lines and tissue samples that underwent oxaliplatin-based treatment. Oxaliplatin resistance-related genes were used to establish a signature. The association of the signature had clinical significance, so the prognostic value of the signature was analyzed. Independent cohorts and CRC cell lines were used to validate the value of the gene signature and the oxaliplatin-resistant genes. There were 64 oxaliplatin resistance-related genes identified after overlapping the genes from the dataset of oxaliplatin-treated CRC cells and the dataset of patients treated with oxaliplatin-based chemotherapy. A gene signature based on five oxaliplatin resistance-related genes was established. This gene signature effectively predicted the prognosis of CRC patients who underwent chemotherapy. No significant associations were found between the gene mutations and survival of the patients; however, two genes were associated with microsatellite instability status. Two external independent cohorts and CRC cell line experiments validated the prognostic values of the signature and expression of the genes after oxaliplatin treatment. In conclusion, the oxaliplatin resistance-related gene signature involving five genes was a novel biomarker for the prediction of the chemotherapy response and prognosis of CRC patients who underwent oxaliplatin-based chemotherapy.

Genomic Analysis Uncovers the Prognostic and Immunogenetic Feature of Pyroptosis in Gastric Carcinoma: Indication for Immunotherapy.

Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.

Nitrogen removal by a strengthened comprehensive floating bed with embedded pellets made by a newly isolated Pseudomonas sp. Y1.

A newly heterotrophic nitrification aerobic denitrification(HN-AD) bacterium Pseudomonas sp. Y1 with highly nitrogen removal ability was isolated from the activated sludge, TN removal rate of which was 99.73%. In this study, two types of different ecology floating bed systems were designed to achieve efficient nitrogen removal in the urban eutrophic landscape water body, one is the comprehensive ecological floating bed(CEFB) system with only Lythrum salicari and the other is the strengthened comprehensive ecological floating bed (SCEFB) system with both Lythrum and embedded pellets made by Y1. The TN removal rates of the CEFB system were 33.82%, 83.84% and 88.91% at 8±1℃, 15±1℃ and 25±1℃, respectively, while the TN removal rates of the SCEFB system increased by nearly 40%, 16% and 11% at the same environment, respectively. The result shows that the SCEFB system can purify the simulated water from surface water body class V to class IV. Thus it has a broad application prospect in the urban eutrophic landscape water body.

Hypoxia-Related Signature Is a Prognostic Biomarker of Pancreatic Cancer.

Background: Hypoxia plays a significant role in the pathogenesis of pancreatic cancer, but the effect of hypoxia-related genes in pancreatic cancer remains to be elucidated. This study aimed to identify hypoxia-related genes related to pancreatic cancer and construct a prognostic signature. Methods: Pancreatic cancer datasets were retrieved from TCGA database. Cox regression analyses were used to identify hypoxia-related genes and construct a prognostic signature. Datasets from International Cancer Genome Consortium and GEO databases were used as validated cohorts. The CIBERSORT method was applied to estimate the fractions of immune cell types. DNA methylation and protein levels of the genes in pancreatic cancer were examined. Results: Three hypoxia-related genes (TES, LDHA, and ANXA2) were identified as associated with patient survival and selected to construct a prognostic signature. Patients were divided into high- and low-risk groups based on the signature. Those in the high-risk group showed worse survival than those in the low-risk group. The signature was shown to be involved in the HIF-1 signaling pathway. The time-dependent ROC analyses of three independent validated cohorts further revealed that this signature had a better prognostic value in the prediction of the survival of pancreatic cancer patients. Immune cells analysis for three datasets demonstrated that high-risk signature was significantly associated with macrophages and T cells. DNA methylation and protein levels of the three genes validated their aberrant expression in pancreatic cancer. Conclusions: Our research provided a novel and reliable prognostic signature that composes of three hypoxia-related genes to estimate the prognosis of pancreatic cancer.

Integrative Analysis Revealed Stemness Features and a Novel Stemness-Related Classification in Colorectal Cancer Patients.

Cancer stem cells play crucial roles in colorectal cancer (CRC) tumorigenesis and treatment response. This study aimed to determine the value of the mRNA stemness index (mRNAsi) in CRC and introduce a stemness-related classification to predict the outcome of patients. mRNAsi scores and RNA sequence data of CRC patients were analyzed. We found that high mRNAsi scores were related to early-stage CRC and a better patient prognosis. Two stemness-based subtypes (subtype I and II) were identified. Patients in subtype I presented a significantly better prognosis than those in subtype II. Patients in these two subtype groups presented significantly different tumor immunity scores and immune cell infiltration patterns. Genomic variations revealed that patients in subtype I had a lower tumor mutation burden than those in subtype II. A three-gene stemness subtype predictor was established, showing good diagnostic value in discriminating patients in different subtypes. A prognostic signature based on five stemness-related genes was established and validated in two independent cohorts and clinical samples, showing a better predictive performance than other clinical parameters. We concluded that mRNAsi scores were associated with the clinical outcome in CRC patients. The stemness-related classification was a promising prognostic predictor for CRC patients.