NPGPx is a member of the glutathione peroxidase (GPx) family; however, it lacks GPx enzymatic activity due to the absence of a critical selenocysteine residue, rendering its function an enigma. Here, ...we show that NPGPx is a newly identified stress sensor that transmits oxidative stress signals by forming the disulfide bond between its Cys57 and Cys86 residues. This oxidized form of NPGPx binds to glucose-regulated protein (GRP)78 and forms covalent bonding intermediates between Cys86 of NPGPx and Cys41/Cys420 of GRP78. Subsequently, the formation of the disulfide bond between Cys41 and Cys420 of GRP78 enhances its chaperone activity. NPGPx-deficient cells display increased reactive oxygen species, accumulated misfolded proteins, and impaired GRP78 chaperone activity. Complete loss of NPGPx in animals causes systemic oxidative stress, increases carcinogenesis, and shortens life span. These results suggest that NPGPx is essential for releasing excessive ER stress by enhancing GRP78 chaperone activity to maintain physiological homeostasis.
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► NPGPx is an ER oxidative stress sensor by forming a Cys57/Cys86 disulfide bond ► Activated NPGPx enhances GRP78 chaperone activity though Cys41/Cys420 formation ► Dysfunction of NPGPx attenuates GRP78 to resolve misfolded protein, and increases ROS ► NPGPx deficiency generates excessive oxidative stress and causes systemic disease
A boron analogue of vinyl cation, pyridine‐stabilized N‐phosphinoamidinato N‐heterocyclic carbene (NHC)‐diboravinyl cation 2+, was synthesized by displacement of bromide in diborene 1 with excess ...pyridine. Experimental and computational studies showed that the positive charge is mainly at the B−B skeleton with delocalization to the pyridine ligand. One of the main modes of reactivity is through the B=B double bond alongside activation of the pyridine substituent, where the Bpyridine center is the predominant nucleophilic center and the predominant electrophilic center is either the activated pyridine para position or the BNHC center, illustrating the presence of diborene cation A, borylene‐borenium cation B and diborene‐pyridinium cation C resonance structures in cation 2+.
A pyridine‐stabilized N‐phosphinoamidinato N‐heterocyclic carbene‐diboravinyl cation was obtained through the displacement reaction of the bromide substituent on a diborene derivative using pyridine. This newly formed species was shown to be a boron analogue of the vinyl cation which could be used for the activation of small molecules.
To understand the origin of the activation barriers of the acyclic dioxycarbene and its heavier congeners, (HCDippN)2BO2G14 (G14=group 14 element), density functional theory calculations were used to ...study their reactivity with dihydrogen and ethene. Our computational results reveal that the insertion reaction of (HCDippN)2BO2G14 with H2 is energetically unfeasible from a kinetic viewpoint. On the other hand, only (HCDippN)2BO2C and (HCDippN)2BO2Si can readily undergo the 1+2 cycloaddition reaction with ethene. The activation strain model (ASM) was used to analyze the present computational results. The theoretical analyses indicate that when a small molecule (H2 or H2C=CH2) reacts with a big molecule ((HCDippN)2BO2G14), the former molecule must undergo a substantial deformation to gain a better overlap of electron density with the latter molecule. This circumstance, in turn, causes a large strain energy (ΔESTR,H2 or ΔESTR,C2H4) to influence the corresponding activation barrier. Accordingly, the heavier the central group 14 atom in (HCDippN)2BO2G14 is, the larger the atomic radius of G14 is, the higher the activation energies for the insertion reaction of (HCDippN)2BO2G14 with dihydrogen and the 1+2 cycloaddition reaction of (HCDippN)2BO2G14 with ethene will be, and the lower the reactivity of (HCDippN)2BO2G14 will be. This finding could help experimental chemists to design novel carbenes possessing fascinating substituents for carbenic chemistry.
Activation strain model (ASM) analysis indicates that the atomic radius of a central group 14 element in an acyclic diboryloxycarbene plays a central role in determining the chemical reactivity of this carbene.
Although refractory high-entropy alloys have exceptional strength at high temperatures, they are often brittle at room temperature. One exception is the HfNbTaTiZr alloy, which has a plasticity of ...over 50% at room temperature. However, the strength of HfNbTaTiZr at high temperature is insufficient. In this study, the composition of HfNbTaTiZr is modified with an aim to improve its strength at high temperature, while retaining reasonable toughness at room temperature. Two new alloys with simple BCC structure, HfMoTaTiZr and HfMoNbTaTiZr, were designed and synthesized. The results show that the yield strengths of the new alloys are apparently higher than that of HfNbTaTiZr. Moreover, a fracture strain of 12% is successfully retained in the HfMoNbTaTiZr alloy at room temperature.
•Both HfMoTaTiZr and HfMoNbTaTiZr alloys have simple BCC structure.•The elevated temperature properties and microstructure evolution of both alloys are investigated.•HfMoNbTaTiZr has better combination of strength and plasticity than HfMoTaTiZr.•The yield strength of HfMoNbTaTiZr is six times that of HfNbTaTiZr at 1200 °C.•HfMoTaTiZr and HfMoNbTaTiZr have great potential in high-temperature applications.
Background
Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer in Asia. Adverse effects occur in over 90% of NPC patients treated with radiotherapy or chemoradiation. Angiotensin ...II receptor blockers (ARBs) are commonly used to treat hypertension without serious adverse effects. However, the anticancer activity of ARBs in NPC remains unclear.
Methods
We investigated the survival impacts of ARBs among NPC patients in a retrospective study. The anticancer effects and related signaling pathways of the ARBs valsartan and losartan were also evaluated in vitro and in vivo.
Result
A total of 927 patients with NPC who had hypertension were enrolled in the study, 272 (29.3%) of whom received ARBs. Kaplan‐Meier analysis revealed that patients who used ARBs had higher rates of 5‐year overall survival (OS; 87.8% vs 75.1%; P = .002) and disease‐specific survival (DSS; 95.4% vs 77.7%; P < .001) than those who did not receive this treatment. Additionally, ARBs inhibited cell proliferation and induced apoptosis by increasing levels of cleaved caspase‐3, cleaved caspase‐9, and cytochrome C; the cell population in the sub‐G1 phase; and caspase‐3 activity in NPC‐TW01 cells. ARBs inhibited tumor growth and angiogenesis via apoptosis in an NPC xenografts model. Interestingly, ARBs inhibited phosphorylation of PI3K/AKT signaling in vitro and in vivo, which is markedly attributed to their antitumor effects in NPC.
Conclusion
These data indicate that ARBs not only improve 5‐year OS and DSS among patients with NPC but also exert antiproliferative and antiangiogenesis effects by inducing apoptosis in NPC, supporting that ARBs may be promising agents for treatment of NPC.
Use of angiotensin II receptor blockers (ARBs) is associated with improved survival in patients who have nasopharyngeal carcinoma (NPC). The ARBs valsartan and losartan suppress tumor growth and angiogenesis in NPC xenografts.
Purpose
The purpose of this study is to investigate the prevalence of pain, pain management, and impact of recent pain on daily functioning in patients with head and neck cancer (HNC) and patients ...with other cancers.
Methods
This multi-center survey was conducted by using Brief Pain Inventory questionnaire to evaluate pain status and its impact on daily functioning.
Results
A total of 3289 patients were analyzed including 708 HNC patients and 2581 patients with other cancers. The overall pain prevalence was 69.17%. A higher percentage of HNC patients had recent pain (60.59 vs. 44.01%,
P
< 0.001), required pain management (86.29 vs. 72.03%,
P
< 0.001), and used any analgesics (53.81 vs. 34.52%,
P
< 0.001). HNC patients with pain management had a higher prevalence of recent pain (85.83 vs. 81.14%,
P
= 0.044) and a slightly lower satisfaction rate (74.00 vs. 79.70%,
P
= 0.070). Regarding the impact of pain on daily functioning, HNC patients had a lower mean interference score for general activity such as walking, normal work, sleep, and life enjoyment.
Conclusions
The HNC patients may need more intensive pain management to achieve optimal pain control and maintain daily functioning.
Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and ...algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2–3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor Nature 574, 505 (2019). We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.
Purpose
Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the ...adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan.
Methods
Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky’s four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses.
Results
Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all
p
< 0.05). Age ≥ 50 years, head and neck or hematological malignancies, cancer-related pain, patients who agreed or strongly agreed that the side effects of analgesic drugs were tolerable, and patients who disagreed or strongly disagreed that the dosing schedule could be flexibly self-adjusted to deal with the actual pain were predictors of good adherence to analgesic drugs.
Conclusions
Awareness of the clinical factors associated with adherence to analgesic drugs may help clinicians to identify cancer patients at a greater risk of non-adherence, reinforce optimal pain management, and improve the QoL by enhancing adherence to pain medications.
Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are ...highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.
The development of white‐light‐emitting electrochemical cells (LECs) has attracted great attention owing to their numerous advantages. Recently, perovskite materials have also shown many outstanding ...optoelectronic properties in light absorption and emission, and hence they are suitable for serving as the color conversion layers (CCLs) in solid‐state white‐light‐emitting diodes (LEDs). Here, white LECs were fabricated by integrating non‐doped blue‐green LECs with CCLs made of a single composition of perovskite nanocrystal (NCs). Moreover, the correlated color temperatures (CCTs) of the white LECs can be tuned by modifying the optical properties of the perovskite NCs, in the same way as so as the color conversion properties of CCLs are tuned, through laser scan. By controlling the laser power, scanning number, and duty cycle of the scanned grating patterns on perovskite‐NC CCLs, the CCTs of the white LECs can be tuned from 2502 K to nearly 4300 K. Since this method is much different from that used with conventional CCLs, which use multiple compositions of perovskite NCs to produce white light, the inherent anion‐exchange issue of perovskite NCs can be avoided.
Tuning light: A laser‐scanning technique was used to modify the color conversion properties of perovskite nanocrystals acting as the color conversion layer in white‐light‐emitting electrochemical cells (LECs). By controlling the scanning conditions, the correlated color temperature of white LECs can be tuned widely (see figure).
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