Supplementary Figure from EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling
Supplementary Figure from EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling
A 2 $\times$ 56 Gb/s 0.78-pJ/b four pulse-amplitude modulation (PAM-4) single-ended multiple-input multiple-output (MIMO) crosstalk cancellation and signal reutilization (XTCR) receiver (RX) is investigated for medium-reach (MR) backplane communications. An XTCR scheme based on active crosstalk extraction (A-XTCR) is proposed to improve the signal reutilization efficiency of the RX. By adopting the proposed asymmetric-inductor current-mode logic (CML) single-ended-to-differential (S2D) converter, the pseudo-differential output mismatch is alleviated. Fabricated in 28-nm CMOS, the RX achieves a bit error rate (BER) of $<$ 1e $-$ 10 at 56-Gb/s PAM-4 transmission with a channel of 24-dB Nyquist loss. Compared with the XTCR based on the conventional passive crosstalk extraction (P-XTCR), the proposed A-XTCR technique has improved vertical and horizontal eye openings of the RX by 24% and 15% at 56-Gb/s PAM-4, respectively. The result corresponds to the best energy efficiency of 0.78 pJ/b/lane, which compares favorably with the state of the art.
<div>Abstract<p>Docetaxel-based chemotherapy is a standard-of-care treatment for metastatic prostate cancer, and chemoresistance remains a major challenge in clinical practice. Recent studies have demonstrated that circular RNAs (circRNA) play critical roles in the development and progression of prostate cancer. However, the biological roles and potential functions of circRNAs in mediating docetaxel-resistant prostate cancer have yet to be well elucidated. In this study, we analyzed the expression profiles of circRNAs in docetaxel-resistant and -sensitive prostate cancer cells through RNA sequencing and found that expression of <i>circARHGAP29</i> was significantly upregulated in docetaxel-resistant cell lines and clinical samples. Ectopic expression of <i>circARHGAP29</i> triggered docetaxel resistance and aerobic glycolysis in prostate cancer cells, which was reduced by silencing <i>circARHGAP29</i>. Moreover, eukaryotic initiation factor 4A3, which bound the back-spliced junction site and the downstream flanking sequence of <i>circARHGAP29</i>, induced cyclization and cytoplasmic export of <i>circARHGAP29</i>. <i>circARHGAP29</i> increased the stability of lactate dehydrogenase A (<i>LDHA</i>) mRNA by strengthening its interaction with insulin-like growth factor 2 mRNA-binding protein 2, leading to enhanced glycolytic metabolism. In addition, <i>circARHGAP29</i> interacted with and stabilized c-Myc mRNA and protein, which further increased LDHA expression by facilitating its transcription. These findings reveal the crucial function of <i>circARHGAP29</i> in prostate cancer glycolysis by increasing and stabilizing <i>LDHA</i> mRNA, providing a promising therapeutic target in docetaxel-resistant prostate cancer.</p>Significance:<p>Upregulation of a novel circRNA, <i>circARHGAP29</i>, promotes docetaxel resistance and glycolytic metabolism, suggesting it could be a prognostic biomarker and therapeutic target in chemoresistant prostate cancer.</p></div>
This paper presents a fully-integrated flipped-voltage-follower-based low-dropout regulator (LDO), with proposed high-gain two-stage cross-coupled error amplifier (XCEA). Besides, the effectiveness of bypass capacitors and diversified load capacitors is discussed. Consuming $\mathbf{170}-\boldsymbol{\mu} \mathbf{A}$ quiescent current and occupying area of 0.019 mm 2 , the LDO features 25-MHz unity-gain bandwidth (UGB) at 20-mA load to satisfy fast response requirement in high-speed transmitter. The simulated voltage undershoot is 38.85 mV for a load transient current stepping from $\mathbf{1}\ \boldsymbol{\mu} \mathbf{A}$ to 25 mA in 50 ps with $\boldsymbol{C}_{\mathbf{L}} =\mathbf{100}\ \mathbf{pF}$ . Owing to the proposed XCEA and the filter capacitor, the PSR is measured to be -41 dB at 100 kHz and -36 dB at 1 MHz.
Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China.We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS.The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd.WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.
Seeking light sources from Si-based materials with an emission wavelength meeting the requirements of optical telecommunication is a challenge nowadays. It was found that the subband emission centered near 1200 nm can be achieved in phosphorus-doped Si quantum dots/SiO2 multilayers. In this work, we propose the phosphorus/boron co-doping in Si quantum dots/SiO2 multilayers to enhance the subband light emission. By increasing the B co-doping ratio, the emission intensity is first increased and then decreased, while the strongest integrated emission intensity is almost two orders of magnitude stronger than that of P solely-doped sample. The enhanced subband light emission in co-doped samples can be attributed to the passivation of surface dangling bonds by B dopants. At high B co-doping ratios, the samples transfer to p-type and the subband light emission from phosphorus-related deep level is suppressed but the emission centered around 1400 nm is appeared.
The growing demand for cloud computing and artificial intelligence applications pushes wireline transceivers to higher data rates. DSP-based transmitters (TX) and receivers (RX) have achieved 224Gb/s [1–2], but unfortunately consume substantial power. Furthermore, 224Gb/s SerDes places more stringent demands on the signal integrity of the passive components, such as connectors, channels, and packages. In contrast, the single-ended scheme may be a practical and cost-effective solution for 224Gb/s data rates. First, it doubles the throughput density by delivering two single-ended signals over one differential channel. Furthermore, this scheme relaxes the Nyquist bandwidth for the passive components. Unfortunately, single-ended links exhibit severe crosstalk, particularly for long-channel scenarios. Previous crosstalk-cancellation (XTC) work [3] cancels the far-end crosstalk (FEXT), but at low data rates. The recent single-ended links achieve 40Gb/s/pin [4], FEXT is minimal but transmission is limited to short distances $(\lt100$ mm). This paper presents a $2 \times 112$ Gb/s PAM-4 single-ended reconfigurable XTC transceiver (TRX) employing a mismatch-mitigation single-ended-to-differential (S2D) converter and a 4-tap RX FFE in 28nm CMOS, compensating for up to 31dB loss at a power efficiency of 2.77pJ/b.
Abstract Epigenetic and transcriptional changes are critical for metastasis, the major cause of cancer-related deaths. Metastatic tumor cells escape immune surveillance more efficiently than tumor cells in the primary sites, but the mechanisms controlling their immune evasion are poorly understood. We found that distal metastases are more immune inert with increased M2 macrophages compared to their matched primary tumors. Acetyl-lysine reader CECR2 is an epigenetic regulator upregulated in metastases and positively associated with M2 macrophages. CECR2 specifically promotes breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting. Mechanistically, NF-κB family member RELA recruits CECR2 to activate CSF1 and CXCL1 , which are critical for macrophage-mediated immunosuppression at the metastatic sites. Furthermore, pharmacological inhibition of CECR2 bromodomain impedes NF-κB-mediated immune suppression by macrophages and inhibits breast cancer metastasis. These results reveal novel therapeutic strategies to treat metastatic breast cancer. Statement of Significance Comparison of matched primary breast tumors and distal metastases show that metastases are more immune inert with increased tumor promoting macrophages. Depletion or pharmacological inhibition of CECR2 inhibits breast cancer metastasis by suppressing macrophage inflammatory responses, nominating CECR2 as a promising therapeutic target for cancer metastasis.
Supplementary Figure from EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling
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