This article presents the 38-GHz phased array 32-element Tx and 16-element Rx with 2-GHz IF and 5-GHz LO for fifth-generation (5G) millimeter-wave (MMW) communications. The Tx and Rx beamformers and ...upconverters/downconverters are fabricated in 65-nm CMOS. The PAs and LNAs near antenna ends are fabricated in 0.15-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> GaAs pHEMT. The eight-element Tx and four-element Rx phased array printed circuit board (PCB) modules integrated with multiple integrated circuits (ICs) and endfire antennas are implemented as unit cells. Four pieces of Tx modules are vertically stacked to construct an <inline-formula> <tex-math notation="LaTeX">8\times {4} </tex-math></inline-formula> brick array (planar array), while four Rx modules are to construct a <inline-formula> <tex-math notation="LaTeX">4\times {4} </tex-math></inline-formula> array. According to 38-GHz over-the-air (OTA) measurements, the 32-element Tx shows 47.5-dBm equivalent isotropic radiated power (EIRP) at OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1 ~dB}} </tex-math></inline-formula> with −35.2-dB image rejection ratio (IMRR) and −37.4-dB <inline-formula> <tex-math notation="LaTeX">\times 8 </tex-math></inline-formula> LORR. The 16-element Rx at 38 GHz shows −4-dBm OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1~dB}} </tex-math></inline-formula> with −28-dB IMRR and −36.6-dB LORR. The Tx and Rx support the beam scanning around ±60° azimuth and ±30° elevation planes. The Tx-to-Rx wireless data link demonstrates 64 quadrature amplitude modulation (QAM)/400 M-BR, 256 QAM/200 M-BR, and 512 QAM/100 M-BR in 20 m. To the best of our knowledge, this work is the first 5G 37-/39-GHz phased array Tx/Rx using the scalable brick array configuration and demonstrating competitive performances compared with previous works.
Syk increases NLRP3 inflammasome formation through phosphorylation of ASC and enhancement of ASC oligomerization.
NLRP3 is the most crucial member of the NLR family, as it detects the existence of ...pathogen invasion and self‐derived molecules associated with cellular damage. Several studies have reported that excessive NLRP3 inflammasome‐mediated caspase‐1 activation is a key factor in the development of diseases. Recent studies have reported that Syk is involved in pathogen‐induced NLRP3 inflammasome activation; however, the detailed mechanism linking Syk to NLRP3 inflammasome remains unclear. In this study, we showed that Syk mediates NLRP3 stimuli‐induced processing of procaspase‐1 and the consequent activation of caspase‐1. Moreover, the kinase activity of Syk is required to potentiate caspase‐1 activation in a reconstituted NLRP3 inflammasome system in HEK293T cells. The adaptor protein ASC bridges NLRP3 with the effector protein caspase‐1. Herein, we find that Syk can associate directly with ASC and NLRP3 by its kinase domain but interact indirectly with procaspase‐1. Syk can phosphorylate ASC at Y146 and Y187 residues, and the phosphorylation of both residues is critical to enhance ASC oligomerization and the recruitment of procaspase‐1. Together, our results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3‐related immune diseases.
HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.
The ERASE-C Campaign is an ...outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up).
At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.
Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.
NCT03803410 and NCT03891550.
High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients ...and analyze the associated factors of persistent cryoglobulinemia.
Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy.
Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio OR- 4.13, 95% Confidence Interval 95% CI- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy.
The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the ...disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibit age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, and are ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO is also rescued by neuronally expressing UQCRC1, but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associates with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increases cyt-c in the cytoplasmic fraction and activates the caspase cascade. Depleting cyt-c or expression of the anti-apoptotic p35 ameliorates uqcrc1-mediated neurodegeneration. Our findings identify a role for UQCRC1 in regulating cyt-c-induced apoptosis.
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•Neuronal reduction of uqcrc1, the ETC complex III subunit, causes PD-like symptoms•uqcrc1 regulates DA neuronal maintenance and locomotor activity in flies•The disease-associated uqcrc1 variant fails to bind cytochrome c, triggering apoptosis•Targeting cytochrome c, but not ROS, ameliorates uqcrc1-mediated neurodegeneration
Point mutations in human UQCRC1 associate with familial parkinsonism, but the underlying mechanisms remain unclear. Using the fruit fly as a model, Hung et al. show that the disease variant fails to retain apoptosis trigger cyt-c in mitochondria, resulting in apoptotic neurodegeneration.
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer ...immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8
T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
Oxaliplatin (OXA), is a third generation platinum drug used as first‐line chemotherapy in colorectal cancer (CRC). Cancer cells acquires resistance to anti‐cancer drug and develops resistance. ...ATP‐binding cassette (ABC) drug transporter ABCG2, one of multidrug resistance (MDR) protein which can effectively discharge a wide spectrum of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular concentration of these drugs. Role of ABCG2 and plausible molecular signaling pathways involved in Oxaliplatin‐Resistant (OXA‐R) colon cancer cells was evaluated in the present study. OXA resistant LoVo cells was developed by exposing the colon cells to OXA in a dose‐dependent manner. Development of multi drug resistance in OXA‐R cells was confirmed by exposing the resistance cells to oxaliplatin, 5‐FU, and doxorubicin. OXA treatment resulted in G2 phase arrest in parental LoVo cells, which was overcome by OXA‐R LoVo cells. mRNA and protein expression of ABCG2 and phosphorylation of NF‐κB was significantly higher in OXA‐R than parental cells. Levels of ER stress markers were downregulated in OXA‐R than parental cells. OXA‐R LoVo cells exposed to NF‐κB inhibitor QNZ effectively reduced the ABCG2 and p‐NF‐κB expression and increased ER stress marker expression. On other hand, invasion and migratory effect of OXA‐R cells were found to be decreased, when compared to parental cells. Metastasis marker proteins also downregulated in OXA‐R cells. ABCG2 inhibitor verapamil, downregulate ABCG2, induce ER stress markers and induces apoptosis. In vivo studies in nude mice also confirms the same.
Present study was designed to evaluate plausible role of ABCG2, multi drug resistance protein and associated pathway involved in OXA‐R LoVo cells. Our data show that oxaliplatin resistant LoVo colon cells are resistant to oxaliplatin, 5‐FU, and doxorubicin. Multi drug resistance acquired by overexpression of ABCG2 and p‐NF‐κB and downregulation of ER stress protein thereby preventing apoptosis.
This paper presents a novel design of compact dualpolarized multi-input and multi-output (MIMO) antennas with endfire radiation for millimeter-wave wireless applications. The low-cost printed circuit ...board process serves as the basis for the design, fabrication, and measurement of the proposed dualpolarized quasi Yagi-Uda antennas. Addressing the potential antenna locations in a mobile terminal, this paper investigates both the corner and the lateral design of antenna modules. Each design incorporates dual-port dual-polarized antennas co-located in a compact area. The lateral design is further extended to a linear 1×4 array for high-gain and phased-scanning operation. Experimental results show that the proposed compact dual-polarized quasi Yagi-Uda antennas are very suitable for MIM terminals of next-generation (5G) mobile communications.
In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.
Subjects admitted ...to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.
There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).
Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pelvic inflammatory disease (PID) is an infectious disease that causes tubal occlusion and other pelvic and abdominal adhesions. The incidence of pelvic inflammatory disease (PID) has increased due ...to the sexually active status of the young population. This leads to a more serious problem and a larger effect than previously observed. However, there have been few studies on this topic in Asian populations.
We aimed to evaluate the risk of preterm labor and/or ectopic pregnancy in Taiwanese women following PID.
Using the Taiwan National Health Insurance Database, we designed a retrospective cohort study that included 12- to 55-year-old pregnant women between 2000 and 2010. We selected a 1:3 age-matched control group of non-PID women. The endpoint was any episode of preterm labor or ectopic pregnancy; otherwise, the patients were tracked until 31 December 2010.
The risk factors for preterm labor or ectopic pregnancy were explored. For cases included from the index date until the end of 2010, we analyzed the risk of incident preterm labor or ectopic pregnancy. With the use of a multivariate Cox proportional hazard regression analysis, we calculated the hazard ratio (HR) with a 95% CI and compared it with that of the control group.
This study examined 30,450 patients with PID and 91,350 controls. During the follow-up period, patients in the PID group were more likely to develop preterm labor or ectopic pregnancy than patients in the control group. The cumulative incidence rates for developing preterm labor were 1.84% (561/30,450 individuals) in patients with PID and 1.63% (1492/91,350 individuals) in patients without PID. On the other hand, the cumulative incidence rate for developing ectopic pregnancy in patients with PID was 0.05% (14/30,450 individuals) but was only 0.04% (33/91,350 individuals) in patients without PID. Compared with those without PID, the patients with PID had a 1.864 times (P<0.001) higher risk of developing preterm labor and a 2.121 times (P = 0.003) higher risk of developing ectopic pregnancy.
Our study provided evidence of an increased risk of preterm labor or ectopic pregnancy in PID patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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