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Background: Lysophosphatidic acids (LPAs) belong to a class of bioactive lysophospholipids with multiple functions including immunomodulatory roles in tumor microenvironment (TME). LPA exerts its biological effects via its receptors that are highly expressed in fibroblasts among other cell types. As cancer‐associated fibroblasts (CAFs) are a key component of the TME, it is important to understand LPA signaling and regulation of receptors in fibroblasts or CAFs and associated regulatory roles on immunomodulation‐related molecules. Methods: Cluster analysis, immunoblotting, real‐time quantitative‐PCR, CRISPR‐Cas9 gene editing system, immunohistochemical staining, coculture model, and in vivo xenograft model were used to investigate the effects of LPA‐LPAR1 on B7‐H3 in tumor promotion of CAFs. Results: In this study, we found that LPAR1 and CD276 (B7‐H3) were generally highly expressed in fibroblasts with good expression correlation. LPA induced B7‐H3 up‐expression through LPAR1, and stimulated fibroblasts proliferation that could be inhibited by silencing LPAR1 or B7‐H3 as well as small molecule LPAR1 antagonist (Ki16425). Using engineered fibroblasts and non‐small cell lung carcinoma (NSCLC) cell lines, subsequent investigations demonstrated that CAFs promoted the proliferation of NSCLC in vitro and in vivo, and such effect could be inhibited by knocking out LPAR1 or B7‐H3. Conclusion: The present study provided new insights for roles of LPA in CAFs, which could lead to the development of innovative therapies targeting CAFs in the TME. It is also reasonable to postulate a combinatory approach to treat malignant fibrous tumors (such as NSCLC) with LPAR1 antagonists and B7‐H3 targeting therapies. [ABSTRACT FROM AUTHOR]

Background: The cytotoxicity of NK cells is largely dependent on IgG Fc receptor CD16a, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). The high-affinity and non-cleavable CD16 (hnCD16) is developed and demonstrated a multi-tumor killing potential. However, the hnCD16 receptor activates a single CD16 signal and provides limited tumor suppression. How to exploit the properties of hnCD16 and incorporate NK cell-specific activation domains is a promising development direction to further improve the anti-tumor activity of NK cells. Methods: To expand the applications of hnCD16-mediated ADCC for NK cell-based immunotherapy in cancer, we designed the hnCD16 Fusion Receptor (FR) constructs with the ectodomain of hnCD16 fused with NK cell-specific activating domains in the cytoplasm. FR constructs were transduced into CD16-negative NK cell line and human iPSC-derived NK (iNK) cells and effective FR constructs were screened. The up-regulation of immune activation- and cytokine-releasing-related pathways in FR-transduced NK cells was screened and validated by RNA sequencing and multiplex cytokines release assay, respectively. The tumor-killing efficiency was tested in vitro and in vivo via co-culture with tumor cell lines and xenograft mice-bearing human B-cell lymphoma, respectively. Results: We screened the most effective combination to kill B cell lymphoma, which was fused with the ectodomain of hnCD16a, NK-specific co-stimulators (2B4 and DAP10) and CD3ζ in cytoplasmic domains. The screened construct showed excellent cytotoxicity effects and sharp multiple cytokines releasing both in the NK cell line and iNK cells. The transcriptomic analysis and validation assays of hnCD16- and hnCD16FR-transduced NK cells showed that hnCD16FR transduction remodeled immune-related transcriptome in NK cells, where significant upregulation of genes related to cytotoxicity, high cytokines releasing, induced tumor cell apoptosis, and ADCC in comparison with hnCD16 transduction were highlighted. In vivo xenograft studies demonstrated that a single low-dose regimen of engineered hnCD16FR iPSC-derived NK cells co-administered with anti-CD20 mAb treatment mediated potent activity and significantly improved survival. Conclusion: We developed a novel hnCD16FR construct that exhibits more potent cytotoxicity than reported hnCD16, which is a promising approach to treat malignancies with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells. [ABSTRACT FROM AUTHOR]

This article presents a new design theory named current harmonics analysis (CHA) for designing load-independent zero voltage switching (LI-ZVS) single-switch resonant dc/dc converters. Compared to the traditional VDS shaping analysis method, the proposed CHA adopts frequency-domain harmonic analysis to eliminate the mathematical iterations and improves ZVS load variation range. The relation between circuit parameters and LI-ZVS characteristics is investigated and discussed. A step-by-step design procedure is developed for the proposed method. Furthermore, the VDS stress is investigated for better engineer practices and its alleviation method without degradation on ZVS feature is proposed and implemented. At last, to validate the design theory, a prototype with single-switch parallel resonant topology, operating at 20-MHz switching frequency for lithium battery chargers is designed, implemented, and verified experimentally. The measured results show a ZVS operation characteristic with a load variation range of 100 times by employing the proposed CHA method, while achieving a conversion efficiency of 92% in a wide load range. To the best of the authors’ knowledge, it is the widest ZVS load variation range compared to previously reported converters. [ABSTRACT FROM AUTHOR]

As an efficient and interference-resistant coding technique, multiple description coding (MDC) is proposed with the aim to solve the transmission unreliability problem caused by packet errors, loss or blocking delays. The integration of MDC with non-orthogonal multiple access (NOMA) scheme (MDC-NOMA) can effectively boost the robustness and throughput of the underlying system. Additionally, space-time block coding (STBC) can further enhance the system reliability with increased diversity gain, as well as reduced decoding complexity. In this paper, we propose a novel framework referred to as MDC-NOMA-STBC, in which we apply Alamouti STBC integrated with MDC and NOMA to implement more reliable transmission. Specifically, NOMA signals are constructed by superimposing the descriptions from different users, then transmitted by the base station (BS) using Alamouti STBC. In order to substantiate the performance of the proposed framework, first, we derive closed-form expressions of both the outage probability and ergodic rate for each user in a two-antenna BS scenario. Second, for multi-antenna BS, we investigate different antenna selection strategies to further enhance the outage performance under the considered framework, whose analytical expression is provided wherever possible. Third, Monte Carlo simulation results are presented to validate our theoretical framework and to corroborate the superiority of the proposed MDC-NOMA-STBC over state-of-the-art MDC-NOMA scheme. Moreover, under realistic contexts with image transmission, it is confirmed that MDC-NOMA-STBC outperforms its counterpart MDC-NOMA in terms of the peak signal-to-noise ratio and the bit error rate. [ABSTRACT FROM AUTHOR]

Although a number of studies have revealed the important roles of miR-34a in cancer, the regulatory roles of miR-34a in cancer immune response remain largely unknown. Our present study demonstrated a mechanism underlying miR-34a-mediated cancer immune evasion via a SIRT1/NF-κB/B7-H3/TNF-α axis. miR-34a upregulated B7-H3, an important immune checkpoint molecule, through direct inhibition of SIRT1 and consequent acetylation of NF-κB subunit p65 (a-p65), which promoted B7-H3 transcription by direct binding to its promoter. The elevated B7-H3 induced production of pro-inflammatory cytokines including TNF-α. This was further confirmed in the colon of Mir34a-deficient mice, where Sirt1 expression was boosted, and the expressions of a-p65, B7h3, and Tnf were repressed. Consequently, the in vivo inhibitory activity of miR-34a on colorectal cancer (CRC) was eradicated by the reinforced B7-H3 and TNF-α. In conclusion, our study uncovered an etiological mechanism underlying miR-34a-mediated CRC immune evasion through inhibition of SIRT1 and promotion of NF-κB/B7-H3/TNF-α axis. [ABSTRACT FROM AUTHOR]

This letter presents a novel technology for the integration of gallium nitride (GaN) power devices with silicon control circuits. It comprises stacked GaN power transistors and bipolar-CMOS-double-diffused metal-oxide-semiconductor (DMOS) (BCD) circuits. It leverages on both advantages of the high-voltage low-loss GaN devices and the high-integration BCD circuits. Using conventional manufacturing, packaging, and assembly techniques and equipment, the proposed technology is technology transferrable and applicable for commercial power electronic applications. To validate the concept, a 3.3–70 V dc–dc boost converter is designed, implemented, and verified experimentally. It features a conversion efficiency of 70.3%, output power of 1.68 W, and compact size of ${\text{0.32}}\times {\text{0.18}}\,{\text{cm}}^{2}$. [ABSTRACT FROM AUTHOR]

Chemotherapeutic regimens containing sorafenib are widely used in salvage treatment for patients with relapsed and refractory acute leukemia, especially those with FLT3-ITD mutations. However, the therapeutic effects in individuals are heterogeneous, and the effective maintenance period is relatively short. Our clinical analysis showed patients with high c-kit (CD117) expression in leukemia cells generally had a better response to sorafenib, but the reason for this finding was not clear. c-kit (CD117) is a receptor tyrosine kinase, and its signal inactivation and hydrolytic metabolism are regulated by the CBL protein, a Ring finger E3 ubiquitin ligase, encoded by the c-CBL gene. And we also found that the c-CBL gene expression in refractory and relapsed patients was significantly lower than that in healthy hematopoietic stem cell donors. Therefore, we assumed that there is a relationship among c-CBL gene function, high expression of c-kit (CD117) and a better clinical response to sorafenib. To confirm this hypothesis, we packaged interfering lentiviruses and overexpressed adenoviruses targeting the c-CBL gene respectively, and infected leukemia cell lines with these viruses to regulate the expression of the c-CBL gene, and observed the subsequent changes of these cells in various biological behaviors. Our results showed when the c-CBL gene was silenced, the cells proliferation was accelerated, drug sensitivity to cytarabine or sorafenib was decreased, and apoptosis ratio was decreased. And all these phenomena were reversed when the gene was overexpressed, which confirmed the expression of c-CBL gene was related to drug resistance in leukemia cells. At last, we explored the possible molecular mechanisms underlying these phenomena. [ABSTRACT FROM AUTHOR]

The use of data envelopment analysis (DEA) in China’s regional energy efficiency and carbon emission efficiency (EE&CE) assessment has received increasing attention in recent years. This paper conducted a comprehensive survey of empirical studies published in 2006–2015 on China’s regional EE&CE assessment using DEA-type models. The main features used in previous studies were identified, and then the methodological framework for deriving the EE&CE indicators as well as six widely used DEA models were introduced. These DEA models were compared and applied to measure China’s regional EE&CE in 30 provinces/regions between 1995 and 2012. The empirical study indicates that China’s regional EE&CE remained stable in the 9th Five Year Plan (1996–2000), then decreased in the 10th Five Year Plan (2000–2005), and increased a bit in the 11th Five Year Plan (2006–2010). The east region of China had the highest EE&CE while the central area had the lowest. By way of conclusion, some useful points relating to model selection are summarized from both methodological and empirical aspects. [ABSTRACT FROM AUTHOR]

This letter presents a compact fully differential branch‐line coupler. It is composed of folded substrate integrated suspended parallel strip line (SISPSL), which can generate slow‐wave effect and help reduce the circuit size. The used SISPSL type line is a fusion of double‐sided parallel‐strip line (DSPSL) and substrate integrated suspended line (SISL), which has the advantage of self‐packaging as compared with traditional DSPSL exposed to air. A DC to 30‐GHz differential transition from grounded coplanar waveguide (GCPW) to SISPSL is designed to test the SISPSL differential coupler. The implemented SISPSL branch‐line coupler has a compact size of 0.056 λg × 0.05 λg. This letter presents a compact fully differential branch‐line coupler using folded substrate integrated suspended parallel strip line (SISPSL), which has a compact size of 0.056 λg × 0.05 λg. A DC to 30‐GHz differential transition from grounded coplanar waveguide (GCPW) to SISPSL is designed to test the SISPSL differential coupler. [ABSTRACT FROM AUTHOR]

The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood ( P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm 3 for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective ( P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients ( P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy ( P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital. [ABSTRACT FROM AUTHOR]

Chromodomain helicase DNA binding protein 5 (CHD5) was previously proposed to function as a potent tumor suppressor by acting as a master regulator of a tumor-suppressive network. CHD5 is down-regulated in several cancers, including leukemia and is responsible for tumor generation and progression. However, the mechanism of CHD5 down-regulation in leukemia is largely unknown. In this study, quantitative reverse-transcriptase polymerase chain reaction and western blotting analyses revealed that CHD5 was down-regulated in human leukemia cell lines and samples. Luciferase reporter assays showed that most of the baseline regulatory activity was localized from 500 to 200 bp upstream of the transcription start site. Bisulfite DNA sequencing of the identified regulatory element revealed that the CHD5 promoter was hypermethylated in human leukemia cells and samples. Thus, CHD5 expression was inversely correlated with promoter DNA methylation in these samples. Treatment with DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates CHD5 expression in human leukemia cell lines. In vitro luciferase reporter assays demonstrated that methylation of the CHD5 promoter repressed its promoter activity. Furthermore, a chromatin immunoprecipitation assay combined with qualitative PCR identified activating protein 2 (AP2) as a potential transcription factor involved in CHD5 expression and indicated that treatment with DAC increases the recruitment of AP2 to the CHD5 promoter. In vitro transcription-factor activity studies showed that AP2 over-expression was able to activate CHD5 promoter activity. Our findings indicate that repression of CHD5 gene expression in human leukemia is mediated in part by DNA methylation of its promoter. [ABSTRACT FROM AUTHOR]

An integrated approach is proposed in this paper to incorporate the group heterogeneity into the framework of natural disposability and managerial disposability, which allows evaluating the CO 2 emission performance under different mitigation strategies (scale-oriented strategy and innovation-oriented strategy). It is able to deal with the intertemporal incomparability when adopting a global technology. In the empirical study, we categorized China's 27 manufacturing sectors into five groups and evaluated their emission performance under different mitigation strategies during 2003–2016. According to the empirical results, we found that there is still much potential (about 70%–80%) for improving the CO 2 emission performance considering the entire manufacturing industry. From the perspective of different groups, the global technologies/innovators group shows the highest emission efficiency, while the energy-/resource-intensive commodities' group performed the worst. Besides, different sectors showed significant technology heterogeneity. Finally, the desirable CO 2 mitigation strategies varied with the different groups. For the labor-intensive tradables' group, we found that the desirable strategy is to decrease the input of energy and other production factors, i.e. scale-oriented strategy. For the regional processing group, the innovation-oriented strategy is more efficient. • Modified global meta-frontier non-radial DDF approach is proposed. • Group heterogeneity is incorporated in natural/managerial disposability framework. • CO 2 emissions performance for China's manufacturing sectors is measured. • Global technologies/innovators group performs best, while energy-/resource-intensive commodities group performs worst. • Desirable mitigation strategies varies with respect to technology heterogeneity of different groups. [ABSTRACT FROM AUTHOR]

Facing the pressure of environment, sustainable development is the demand of the current construction industry development. Prefabricated construction technologies has been actively promoted in China. Cost has always been one of the important factors in the development of prefabricated buildings. The hidden cost of prefabricated buildings has a great impact on the total cost of the project, and it exists in the whole process of building construction. In this paper innovatively studies the cost of prefabricated buildings from the perspective of hidden cost. In order to analysis the hidden cost of prefabricated buildings, the influencing factor index system in terms of design, management, technology, policy and environment has been established, which includes 13 factors in total. And the hidden cost analysis model has been proposed based on FISM-BN, this model combines fuzzy interpretive structure model(FISM) with Bayesian network(BN). This model can comprehensively analyze the hidden cost through the combination of qualitative and quantitative methods. And the analysis process is dynamic, not fixed at a certain point in time to analyze the cost. We can get the internal logical relationship among the influencing factors of the hidden cost, and present it in the form of intuitive chart by FISM-BN. Furthermore the model could not only predict the probability of the hidden cost of prefabricated buildings and realize in-time control through causal reasoning, but also predict the posterior probability of other influencing factors through diagnostic reasoning when the hidden cost occurs and find out the key factors that lead to the hidden cost. Then the final influencing factors are determined after one by one check. Finally, the model is demonstrated on the hidden cost analysis of prefabricated buildings the probability of recessive cost is 26%. In the analysis and control of the hidden cost of prefabricated buildings, scientific and effective decision-making and reference opinions are provided for managers. [ABSTRACT FROM AUTHOR]

We present 500 and 700 au resolution 1 and 3 mm Atacama Large Millimeter/submillimeter Array observations, respectively, of protostellar cores in protoclusters Sagittarius B2 (Sgr B2) North (N) and Main (M), parts of the most actively star-forming cloud in our Galaxy. Previous lower-resolution (5000 au) 3 mm observations of this region detected ∼150 sources inferred to be young stellar objects (YSOs) with M > 8 M ⊙. With a 10-fold increase in resolution, we detect 371 sources at 3 mm and 218 sources in the smaller field of view at 1 mm. The sources seen at low resolution are observed to fragment into an average of two objects. About one-third of the observed sources fragment. Most of the sources we report are marginally resolved and are at least partially optically thick. We determine that the observed sources are most consistent with Stage 0/I YSOs, i.e., rotationally supported disks with an active protostar and an envelope, that are warmer than those observed in the solar neighborhood. We report source-counting-based inferred stellar mass and the star formation rate of the cloud: 2800 M ⊙ and 0.0038 M ⊙ yr−1 for Sgr B2 N and 6900 M ⊙ and 0.0093 M ⊙ yr−1 for Sgr B2 M, respectively. [ABSTRACT FROM AUTHOR]

We studied the unique kinematic properties in massive filament G352.63-1.07 at 103 au spatial scale with the dense molecular tracers observed with the Atacama Large Millimeter/submillimeter Array. We find the central massive core M1 (12 M ⊙) being separated from the surrounding filament with a velocity difference of v − v ¯ sys = − 2 km s − 1 and a transverse separation within 3″. Meanwhile, as shown in multiple dense-gas tracers, M1 has a spatial extension closely aligned with the main filament and is connected to the filament toward both its ends. M1 thus represents a very beginning state for a massive, young star-forming core escaping from the parental filament, within a timescale of ∼4000 yr. Based on its kinetic energy (3.5 × 1044 erg), the core escape is unlikely solely due to the original filament motion or magnetic field but requires more energetic events such as a rapid intense anisotropic collapse. The released energy also seems to noticeably increase the environmental turbulence. This may help the filament to become stabilized again. [ABSTRACT FROM AUTHOR]

Fast Radio Bursts (FRBs) are millisecond-duration transient events that are typically observed at radio wavelengths and cosmological distances but their origin remains unclear. Furthermore, most FRB origin models are related to the processes at stellar scales, involving neutron stars, blackholes, supernovae, etc. In this paper, our purpose is to determine whether multi-structural one-off FRBs and repeaters share similarities. To achieve this, we focus on analyzing the relationship between the FRB event rate and the star formation rate, complemented by statistical testing methods. Based on the CHIME/FRB Catalog 1, we calculate the energy functions for four subsamples, including apparent non-repeating FRBs (one-offs), repeaters, multi-structural one-offs, and the joint repeaters and multi-structural events, respectively. We then derive the FRB event rates at different redshifts for all four subsamples, all of which were found to share a similar cosmological evolution trend. However, we find that the multi-structural one-offs and repeaters are distinguishable from the KS and MWW tests. [ABSTRACT FROM AUTHOR]

In this paper, the stress memorization technique (SMT) effects upon ultra-wideband RF switch performance are investigated for the first time. Low insertion loss (IL), high isolation, ultra-wideband (dc to 50 GHz) single-pole double-throw (SPDT), and single-pole four-throw (SP4T) switches designed with commercial 0.13- \mu \textm high-resistivity (HR) trap-rich SOI technology with/without SMT are presented and investigated. 2.5 V nMOS transistor ( Lg = 0.2~\mu \text{m} ) with low R\mathrm{\scriptscriptstyle ON} {^\ast} C\mathrm{\scriptscriptstyle OFF} from GF 130RFSOI PDK is used. It is found that channel mobility of switch transistor is improved by SMT and thus switch performance can be further improved. Moreover, the impact of transistor channel length, which has dominant effects on both IL and isolation of the switches, under different gate bias on switch performance are also studied and verified experimentally. Low measured IL of less than 2.1 dB and good isolation of better than 27 dB from dc to 50 GHz are obtained for the SPDT switch. For SP4T switch, the measured IL of less than 2.6 dB and isolation of better than 27 dB are achieved from dc to 35 GHz. The active chip areas of designed SPDT and SP4T switches are compact with size of only 0.214 \times 0.19~\text mm^2 and 0.36 \times 0.19~ \text mm^2 , respectively. [ABSTRACT FROM AUTHOR]

This paper presents low insertion loss, high isolation, ultra-wideband double-pole-double-throw (DPDT) switch matrix designed in a 0.13- \mu \textm commercial high resistivity trap-rich silicon-on-insulator (SOI) CMOS process for the first time. The switches are designed using series–shunt–series configuration in a ring-type structure with input and output matching networks. Transistor width and transistor channel length effects on the wideband DPDT switch performance are thoroughly investigated. The designed switches achieve widest bandwidth from dc to 30 GHz with a low insertion loss of 2.5 dB and a high isolation of 32 dB up to 30 GHz. The measured input P1dB of designed switches is higher than 18 dBm. It was found both second and third harmonics can be improved by widening switch transistor channel width, and third harmonic can be improved by shortening channel length. The active chip area of designed $2 \times2$ switch matrix is very small size of only 0.28 mm $\times0.21$ mm. [ABSTRACT FROM PUBLISHER]

This paper presents two devices to detect the liquid dielectric characterization. The differential method was used to enhance the robustness and reduce tolerance. A basic sensor based on defected ground structure (DGS) was designed and the optimization for the squares of the DGS via adaptive genetic algorithm was applied to enhance the performance of the microwave sensor, which was shown by the difference of the two resonant frequencies. Furthermore, the electric field distribution was enhanced. Glass microcapillary tubes were used to hold samples to provide an environment of non-invasive. The optimized device exhibited the sensitivity of 0.076, which is more than 1.52 times than the basic structure. It could be considered a sensitive and robust sensor with quick response time for liquid dielectric characterization. [ABSTRACT FROM AUTHOR]

In this paper, the extraction of the life activity spectrum based on the millimeter (mm) wave radar is designed to realize the detection of target objects and the threshold trigger module. The maximum likelihood estimation method is selected to complete the design of the average early warning probability trigger function. The threshold trigger module is designed for the echo signal of static objects in the echo signal. It will interfere with the extraction of Doppler frequency shift results. The moving target detection method is selected, and the filter is designed. The static clutter interference is filtered without affecting the phase difference between the detection sequences, and the highlight target signal is improved. The frequency and displacement of thoracic movement are used as the detection data. Through the Fourier transform calculation of the sequence, the spectrum value is extracted within the estimated range of the heartbeat and respiration spectrum, and the heartbeat and respiration signals are picked up. The proposed design uses Modelsim and Quartus for CO-simulation to complete the simulation verification of the function, extract the number of logical units occupied by computing resources, and verify the algorithm with the vital signs experiment. The heartbeat and respiration were detected using the sports bracelet; the relative errors of heartbeat detection were 0–6.3%, the respiration detection was 0–9.5%, and the relative errors of heartbeat detection were overwhelmingly less than 5%. [ABSTRACT FROM AUTHOR]

Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6–14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52–54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately. [ABSTRACT FROM AUTHOR]

Background: Epigenetic dysregulation plays important roles in leukemogenesis and the progression of acute myeloid leukemia (AML). Histone acetyltransferases (HATs) and histone deacetylases (HDACs) reciprocally regulate the acetylation and deacetylation of nuclear histones. Aberrant activation of HDACs results in uncontrolled proliferation and blockade of differentiation, and HDAC inhibition has been investigated as epigenetic therapeutic strategy against AML.Methods: Cell growth was assessed with CCK-8 assay, and apoptosis was evaluated by flow cytometry in AML cell lines and CD45 + and CD34 + CD38- cells from patient samples after staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI). EZH2 was silenced with short hairpin RNA (shRNA) or overexpressed by lentiviral transfection. Changes in signaling pathways were detected by western blotting. The effect of chidamide or EZH2-specific shRNA (shEZH2) in combination with adriamycin was studied in vivo in leukemia-bearing nude mouse models.Results: In this study, we investigated the antileukemia effects of HDAC inhibitor chidamide and its combinatorial activity with cytotoxic agent adriamycin in AML cells. We demonstrated that chidamide suppressed the levels of EZH2, H3K27me3 and DNMT3A, exerted potential antileukemia activity and increased the sensitivity to adriamycin through disruption of Smo/Gli-1 pathway and downstream signaling target p-AKT in AML cells and stem/progenitor cells. In addition to decreasing the levels of H3K27me3 and DNMT3A, inhibition of EZH2 either pharmacologically by chidamide or genetically by shEZH2 suppressed the activity of Smo/Gli-1 pathway and increased the antileukemia activity of adriamycin against AML in vitro and in vivo.Conclusions: Inhibition of EZH2 by chidamide has antileukemia activity and increases the chemosensitivity to adriamycin through Smo/Gli-1 pathway in AML cells (Fig. 5). These findings support the rational combination of HDAC inhibitors and chemotherapy for the treatment of AML. [ABSTRACT FROM AUTHOR]

B7-H3, an important co-inhibitor, is abnormally highly expressed in a variety of malignancies. The antibodies targeting B7-H3 have exhibited beneficial therapeutic effects in clinical trials. Therefore, discovery of the regulatory factors in B7-H3 expression may provide new strategies for tumor therapy. Here, we investigated the splicing factors involved in the splicing of B7-H3. By individual knockdown of the splicing factors in colorectal cancer (CRC) cells, we found that B7-H3 expression was markedly inhibited by SRSF3 and SRSF8, especially SRSF3. Then we found that both SRSF3 and B7-H3 were highly expressed in CRC tissues. Moreover, high-expression of either SRSF3 or B7-H3 was significantly correlated with poor prognosis of patients. The expression of B7-H3 mRNA and protein were evidently reduced by SRSF3 silence, but were enhanced by overexpression of SRSF3 in both HCT-116 and HCT-8 cells. The results from the RNA immunoprecipitation (RIP) assays demonstrated that SRSF3 protein directly binds to B7-H3 mRNA. In addition, we constructed a minigene recombinant plasmid for expressing B7-H3 exons 3–6. We found that SRSF3 contributed to the retention of B7-H3 exon 4. These findings demonstrate that SRSF3 involves in the splicing of B7-H3 by directly binding to its exon 4 and/or 6. It may provide novel insights into the regulatory mechanisms of B7-H3 expression and potential strategies for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Hedgehog (Hh) signaling is involved in the pathogenesis of tumors. By performing gene chip analysis, we predicted that Hh signaling might regulate multiple downstream pathways in acute myeloid leukemia (AML). Methods: In this study, the potential role of the Hh pathway in refractory AML, and the impact of Hh expression on clinical prognosis were examined. We also investigated the role of the Hh inhibitor NVP-LDE225 in reversing drug resistance of refractory primary AML cells in vitro and the roles of multiple drug-resistant HL60/Adriamycin-resistant cells in vitro and in vivo (in a xenograft mouse model). Finally, we explored the underlying mechanisms. Results: Hh pathway was highly active in chemotherapy-resistant AML cells; by contrast, activation was less pronounced in chemosensitive cells and non-refractory primary cells. Strong activation of this pathway was associated with higher recurrence rates and poorer relapse-free and overall survival. NVP-LDE225 inhibited MRP1 protein expression, increased intracellular accumulation of Adriamycin, and reversed chemotherapeutic resistance. These effects were likely mediated through inhibition of the IGF-1R/Akt/MRP1 pathway. In the AML xenograft mouse model, NVP-LDE225 plus Adriamycin resulted in marked tumor regression. Conclusion: These findings suggest that targeting the Hh pathway might be a therapeutic avenue for overcoming MDR resistance and preventing refractory AML. [ABSTRACT FROM AUTHOR]

Extramedullary infiltration (EMI) is common in patients with acute myeloid leukemia (AML) and is closely associated with the prognosis of disease. We previously reported that patients carrying the AML1/ETO (A/E) fusion gene and expressing the amyloid precursor protein (APP) tended to develop EMI, and had a poor prognosis. In the present study, the relapse-free survival (RFS) time and overall survival (OS) time were significantly lower in patients with EMI. The results demonstrated that the EMI incidence was significantly higher (P<0.05), while the RFS and OS rates were significantly lower (P<0.05), in patients with high APP expression. Kasumi-1 cells, which are A/E+, and the APP gene were used as the in vitro cell model to detect the mechanism of action in detail. Following the knockdown of APP expression, cell migration was significantly reduced (P<0.05). Furthermore, western blotting demonstrated that the protein expression of phosphorylated extracellular-signal-regulated kinase (p-ERK), matrix metalloproteinase-2 (MMP-2) and c-Myc was markedly reduced following interference of APP, while the expression of CXCR4 and MMP-9 was not altered. Kasumi-1 cells were co-cultured with p-ERK or c-Myc inhibitors and demonstrated that the APP/p-ERK/c-Myc/MMP-2 pathway was involved in signal transduction and regulation of cell migration. MicroRNA-144 (miR-144) mimics and transfected Kasumi-1 cells were generated. Reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that miR-144 was a negative regulator of APP. Taken together, the findings of the present study suggest that miR-144 negatively targets the APP gene and regulates cell migration via the APP/p-ERK/c-Myc/MMP-2 pathway. [ABSTRACT FROM AUTHOR]

A fully integrated 93.4–104.8-GHz 57-mW fractional- ${N}$ cascaded phase-locked loop (PLL) with true in-phase injection-coupled quadrature voltage-controlled oscillator (QVCO) is reported. By cascading the fractional- ${N}$ PLL and the subsampling PLL, good phase noise, high resolution, and wide acquisition range are achieved simultaneously. The transformer-based true in-phase injection coupled technique is adopted in the QVCO to obtain both low phase noise and low-power consumption. The proposed cascaded PLL was fabricated in a 65-nm CMOS technology with silicon size of 0.88 mm2. The measured phase noise of QVCO and PLL is −113.26 and −106.63 dBc/Hz at 10-MHz offset, respectively. The FOM and FOMT of the QVCO at 10-MHz offset are −178.4 and −180.0 dBc/Hz, respectively. The frequency resolution of the 100-GHz output is less than 3.6 kHz. [ABSTRACT FROM AUTHOR]

The representation and processing of uncertainty knowledge are among the most commonly investigated problems in the rough set theory. In this paper, we apply the rough set theory to analyze the phase uncertainty of multi-tone stimulus scheme for nonlinear vector network analyzer (NVNA) phase reference frequency response in hybrid information system (HIS). Matlab was used to process the oscilloscope-based measured data for time and frequency response. The phase uncertainty experimental results revealed a significant correlation between the standard uncertainty and the response amplitude. Additionally, the lower amplitude in spectrum corresponded to higher phase uncertainty and vice versa. The proposed multi-tone stimulus scheme provides high resolution and rich intermodulation components around each harmonic for NVNA phase reference standard in HIS. The measured results were in good agreement with the theoretical formula-based results, and therefore, confirmed the validity of the proposed work. [ABSTRACT FROM AUTHOR]

Amyloid precursor protein (APP) has been reported to be highly expressed in acute myeloid leukemia (AML)1-eight-twenty one (ETO)-positive AML. In the present study, the clinical and prognostic significance of APP expression was assessed in 65 patients with AML1-ETO-positive AML using reverse transcription-quantitative polymerase chain reaction. The patients were divided into an APP-high expression (APP-H) group (n=32) and an APP-low expression (APP-L) group (n=33) according to the cut-off value of APP relative expression, which was calculated by receiver operating characteristic curve analysis. It was observed that C-KIT mutations (14/32 vs. 3/33, P=0.009), white blood cell count (median, 23.2x109 vs. 12.4x109 cells/l; P=0.011) and bone marrow cellularity (median, 91.0 vs. 84.0%; P=0.039) and incidence of extramedullary leukemia (11/32 vs. 3/33, P=0.013) were all significantly increased in the APP-H group compared with the APP-L group. Furthermore, significantly lower rate of cumulative two-cycle complete remission (83.9 vs. 100%, P=0.016), major molecular remission following two courses of consolidation (34.5 vs. 71.4%, P=0.005), and poorer relapse-free survival (RFS) (33.5±5.2% vs. 76.3±6.9%, P<0.001) and overall survival (OS) (44.5±7.0% vs. 81.9±5.8%, P=0.002) were associated with APP overexpression. Multivariate analysis revealed that APP overexpression was a significant adverse factor affecting both RFS and OS. Taken together, these data suggest that APP may be correlated with C-KIT mutations and involved in leukemia cell proliferation, and its overexpression has an adverse effect on the prognosis in AML1-ETO-positive AML. [ABSTRACT FROM AUTHOR]

Quasi-lumped-element low-pass filter (LPF) and high-pass filter (HPF) based on substrate-integrated suspended line (SISL) technology are presented in this paper. Double interdigital capacitor, which has advantages of high capacitance density and high quality factor, is analyzed and designed to minimize the filter size. Based on the theoretical analysis, quasi-lumped-element SISL LPF and HPF prototypes are designed. The experimental results show that the SISL LPF achieves ultra-wide stopband up to 24 \textfc ( \textfc is the cut-off frequency) with compact size of 0.180~\lambda g \times 0.082~\lambda g ( \lambda g is the guide wavelength at \textfc) . The SISL HPF features the low insertion loss of only 0.3 dB, while the size is only 0.108~\lambda g \times 0.085~\lambda g . Moreover, the methods of substrate excavation and packaging optimization are proposed to further enhance the performance of SISL LPF and SISL HPF. By doing so, the stopband of SISL LPF is further extended to 32 fc, and the insertion loss of SISL HPF is significantly reduced to 0.1 dB. [ABSTRACT FROM PUBLISHER]

The paper proposes a survey on three issues related to Strategic Petroleum Reserves (SPR) policy. Firstly, what are the optimal SPR acquisition, drawdown and refilling policy in response to various market risks? Secondly, how SPR policy or actions will affect the market factors, i.e. oil demand or price. Thirdly, in what extend a disruption may induce price shock. For the purpose, the study proposed a Markov Decision Process model (SPR-MDP). In the model, oil supply, disruption size and duration are considered to be highly stochastic. Oil price is determined by market fundamentals exclusively. According to the empirical study, we come to some interesting conclusions. Firstly, oil price and disruption risk show different ways in influencing the desirable SPR size. It is found that the SPR size increases with the decrease of oil price while increase of disruption risk. Secondly, SPR acquisition may increase oil price slightly by influencing the basic fundamentals. In given case, we find acquisition of 7 million barrels per month increase the price by 2.6%. But the influence weakens with decrease of acquisition size. Thirdly, disruption duration shows significant impact on SPR drawdown policy. In a two-month disruption case, it is found that 51% of SPR should be released in the first month. Another 40% is released in the following month. The other 9% SPR is left for forthcoming disruptions. Meanwhile, SPR drawdown shows high efficient in damping oil price in the disruption. In given case, after drawdown of SPR, the oil prices only increases by 0.7% in the second month though continue disruption. [ABSTRACT FROM AUTHOR]

Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly+AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly−AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly+AML and Ly−AML. With regard to the patients with normal karyotype only, the OS and RFS of MPAL were significantly lower than those of the Ly+AML and Ly−AML; but there were no significant differences in OS and RFS among the patients with complex karyotype. The OS rates of 3 groups with complex karyotype were lower than those of patients with normal karyotype. In Cox multivariate analysis, complex karyotype was an independent pejorative factor for both OS and RFS. Therefore, MPAL is confirmed to be a poor-risk disease while Ly+AML does not impact prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients with different immunophenotype. Mixed immunophenotype and complex karyotype increase the adverse risk when they coexist. [ABSTRACT FROM AUTHOR]

Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML. [ABSTRACT FROM AUTHOR]

• Optimal dietary chromium (1.22 mg/kg) improved growth of L. vannamei. • Chromium trigger glycolysis and glycogenesis and suppress gluconeogenesis to maintain glucose homeostasis. • Excess chromium (1.63 mg/kg) caused oxidative damage and apoptosis in L. vannamei. While chromium (Cr) has been recognized as an essential nutrient for all animals, and dietary supplementation can be beneficial, it can also be toxic. The present study aimed to investigate the contrasting effects of dietary chromium in Pacific white shrimp Litopenaeus vannamei. Five experimental diets were formulated to contain Cr at levels of 0.82 (Cr0.82, unsupplemented diet), 1.01 (Cr1.01), 1.22 (Cu1.22), 1.43 (Cr1.43) and 1.63 (Cr1.63) mg/kg and were fed to shrimp for 8 weeks. Highest weight gain was recorded in shrimp fed the diet containing 1.22 mg/kg Cr. Shrimp fed the diet containing the highest level of Cr (1.63 mg/kg) showed the lowest weight gain and clear signs of oxidative stress and apoptosis as evidenced by higher levels of H 2 O 2 , malondialdehyde and 8-hydroxydeoxyguanosine, and expression of caspase 2, 3, 5, and lower contents of total and oxidized glutathione, and expression of Cu/Zn sod, cat, gpx, mt, bcl2. Chromium supplementation promoted glycolysis and inhibited gluconeogenesis as shown by increased activities of hexokinase, phosphofructokinase and pyruvate kinase, and reduced activity of phosphoenolpyruvate carboxykinase in shrimp fed the diet containing 1.43 mg/kg Cr. Shrimp fed the diet with 1.63 mg/kg Cr had lowest contents of crustacean hyperglycemic hormone and insulin like peptide in hemolymph. Expression of genes involved in insulin signaling pathway and glycose metabolism including insr, irs1, pik3ca, pdpk1, akt, acc1, gys, glut1, pk, hk were up-regulated, and foxO1, gsk-3β, g6pc, pepck were down-regulated in shrimp fed the diets supplemented with Cr. This study demonstrated that optimum dietary supplementation of Cr had beneficial effects on glucose homeostasis and growth, whereas excess caused oxidative damage and impaired growth. The results contribute to our understanding of the biological functions of chromium in shrimp. [ABSTRACT FROM AUTHOR]

A survey toward 674 Planck cold clumps of the Early Cold Core Catalogue (ECC) in the J = 1-0 transitions of 12CO, 13CO, and C18O has been carried out using the Purple Mountain Observatory 13.7 m telescope. Six hundred seventy-three clumps were detected with 12CO and 13CO emission, and 68% of the sample has C18O emission. Additional velocity components were also identified. A close consistency of the three line peak velocities was revealed for the first time. Kinematic distances are given for all the velocity components, and half of the clumps are located within 0.5 and 1.5 kpc. Excitation temperatures range from 4 to 27 K, slightly larger than those of Td. Line width analysis shows that the majority of ECC clumps are low-mass clumps. Column densities span from 1020 to 4.5 × 1022 cm–2 with an average value of (4.4 ± 3.6) × 1021 cm–2. cumulative fraction distribution deviates from the lognormal distribution, which is attributed to optical depth. The average abundance ratio of the 13CO to C18O in these clumps is 7.0 ± 3.8, higher than the terrestrial value. Dust and gas are well coupled in 95% of the clumps. Blue profile asymmetry, red profile asymmetry, and total line asymmetry were found in less than 10% of the clumps, generally indicating that star formation is not yet developed. Ten clumps were mapped. Twelve velocity components and 22 cores were obtained. Their morphologies include extended diffuse, dense, isolated, cometary, and filament, of which the last is the majority. Twenty cores are starless, and only seven cores seem to be in a gravitationally bound state. Planck cold clumps are the most quiescent among the samples of weak red IRAS, infrared dark clouds, UC H II candidates, extended green objects, and methanol maser sources, suggesting that Planck cold clumps have expanded the horizon of cold astronomy. [ABSTRACT FROM AUTHOR]

Multiple-input multiple-output (MIMO) radar is playing an important role in military and civilian fields. However, radio frequency (RF) multi-links have a large data-processing capacity and the system is bulky and complex. Therefore, a single-link RF MIMO has been the subject of heated discussed in recent years. Single-link technology shares the same regularity with that of the multi-link MIMO system, which makes the MIMO system simpler in structure without affecting its performance. In this study, a 2 × 2 array single RF link MIMO radar at X band was designed by combining MIMO radar with the concept of a single RF link in the communication field, and a simulation platform for studying its properties was established using SystemVue software. The whole system is controlled by the exclusive OR (XOR) operation results of two transmission signals, and one signal can control the antenna-switching signal to form a variety of orthogonal bases. The received two original signals are demodulated and the control signals enter the corresponding matched filters. The signal is processed by fast Fourier transformation (FFT) and the cell-averaging constant false alarm rate algorithm (CA-CFAR) is used to judge the signal. For multiple measurements, the Monte Carlo method was adopted to obtain its mean value as the final result. Compared with the traditional MIMO radar performance in acquiring the target position, speed, and detection probability, the results show that the computation time can be greatly reduced (due to decrease in the number of links in MIMO radar system) without any deterioration in the MIMO radar performance. The single RF link technology provides a broad prospect for the miniaturization of small radar applications. [ABSTRACT FROM AUTHOR]