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The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses. Here Zhao et al. report a promising broad-spectrum antiviral alkaline peptide—P9R—that is active against several respiratory, pH-dependent viruses, including Influenza and SARS-CoV-2. P9R interferes with virus internalization by binding to the virus and subsequent inhibition of endosomal acidification.

Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19. Until today effective antivirals for COVID-19 treatment are not widely available. Here, Zhao et al. characterize a dual-functional cross-linking peptide, 8P9R, that can inhibit SARS-CoV-2 virus entry in vitro and suppresses viral replication in vivo in golden Syrian hamster.

The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell-cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.

Programmable metasurfaces (PMSs) exhibit great potentials in target detection techniques, because they can take actions to change channel propagation characteristics which introduces further degrees of freedom for system optimizations. However, responses of most traditional PMSs are sensitive to incident angles of impinging electromagnetic waves, resulting in a failure of angular estimation to dynamic targets coming from different directions. Herein, by proposing a fully resonant structure and introducing a mode-alignment technology, we report an isotropic angle-insensitive PMS whose phase response is stable with respect to different incident angles in both elevation- and azimuth-planes. A radar scheme that uses such a PMS as a periscope is also demonstrated, to detect drones in a non-line-of-sight (N-LOS) scenario which usually happens in an urban environment. Our proposed scheme enables those targets even falling in shadow areas caused by high buildings to be successfully detected and tracked, which shows promising potentials in N-LOS target detections. An isotropic angle-insensitive PMS is reported by proposing a fully resonant structure and introducing a mode-alignment technology. A radar scheme that uses such a PMS as a periscope shows promising potentials in N-LOS target detections.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with the high transmissibility and increased immune escape against vaccines. Because of the multiple basic amino acids in the S1-S2 junction of spike protein, the widespread distribution of angiotensin-converting enzyme 2 (ACE2) receptor in human body and the high transmissibility, SARS-CoV-2 can infect multiple organs and has led to over 0.7 billion infectious cases. Studies showed that SARS-CoV-2 infection can cause more than 10% patients with the Long-COVID syndrome, including pathological changes in brains. This review mainly provides the molecular foundations for understanding the mechanism of SARS-CoV-2 invading human brain and the molecular basis of SARS-CoV-2 infection interfering with human brain and memory, which are associated with the immune dysfunction, syncytia-induced cell death, the persistence of SARS-CoV-2 infection, microclots and biopsychosocial aspects. We also discuss the strategies for reducing the Long-COVID syndrome. Further studies and analysis of shared researches will allow for further clarity regarding the long-term health consequences.

Singlet oxygen ( 1 O 2 ), one of the most sought-after species in oxidative chemical reactions and photodynamic cancer therapy, is activated and neutralized in the atmosphere and living cells. It is essential to see \"when\" and \"where\" 1 O 2 is produced and delivered to understand and utilize it. There is an increasing demand for molecular sensor tools to capture, store, and supply 1 O 2 , controlled by light and engineered singlet and triplet states, indicating the 1 O 2 -capturing-releasing state. Here, we demonstrate the outstanding potential of an aminocoumarin-methylanthracene-based electron donor–acceptor molecule ( 1 ). Spectroscopic measurements confirm the formation of an endoperoxide ( 1-O 2 ) which is not strongly fluorescent and remarkably different from previously reported 1 O 2 sensor molecules. Moreover, the photoexcitation on the dye in 1-O 2 triggers fluorescence enhancement by the oxidative rearrangement and a competing 1 O 2 release. The unique ability of 1 will pave the way for the spatially and temporally controlled utilization of 1 O 2 in various areas such as chemical reactions and phototherapies.

The time-domain coding metasurface (TDCM) offers a rapid and efficient approach for manipulating frequency spectra of electromagnetic waves. To date, not only finite-order harmonics can be generated and coded discretely, frequency modulation of continuous waves has also been investigated. However, limited phase-tuning speed still constrains the modulation bandwidth and practical applications. Here, we report a TDCM capable of nanosecond-level phase tuning as fast as 20 ns within a full 360° tuning cycle. Unlike conventional varactor-based approaches, the proposed TDCM adopts a reconfigurable PIN-diode array, reducing transition time between adjacent states to only several nanoseconds. Furthermore, this approach can be extended to Ku - and even millimeter-wave bands, overcoming the frequency constraint of varactors. To validate its effectiveness, we built a C -band frequency-modulated continuous-wave radar prototype with the metasurface as the signal generator. A high-quality 10-MHz-bandwidth FMCW signal was generated, enabling accurate measurement of a flying drone’s range and speed. A nanosecond-level time-coding metasurface is proposed to achieve rapid phase tuning and high-quality radar signal generation, allowing precise detection of small, slow-moving targets and opening new possibilities for advanced radar applications.

Guidewire entrapment (GE) is a rare complication that warrants complex interventions or surgical procedures. Here, we report the removal of an entrapped guidewire using excimer laser coronary angioplasty (ELCA) in a case of chronic total occlusion (CTO). Plaque tissue trapped with the guidewire was also removed. Histopathological examination revealed that although specific components were entrapped with the guidewire, loosening the adjacent collagen fibres during ELCA contributed to the successful removal of the guidewire. This case showed that ELCA may be a novel modality for the removal of an entrapped guidewire in cases of CTO.

Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating the photosensitizer rTPA into MITO-Porter (MP), a mitochondria-targeted Drug Delivery System (DDS), aimed at mitochondrial delivery of the photosensitizer while maintaining its activity. In this study, we report the results of our studies to alleviate rTPA aggregation in an effort to improve drug efficacy and assess the usefulness of modifying the rTPA side chain to improve the mitochondrial retention of MITO-Porter, which exhibits high therapeutic efficacy. Conventional rTPA with anionic side chains and two rTPA analogs with side chains that were converted to neutral or cationic side chains were encapsulated into MITO-Porter. Low-MP (MITO-Porter with Low Drug/Lipid) exhibited high drug efficacy for all three types of rTPA, and in Low-MP, charged rTPA-encapsulated MP exhibited high drug efficacy. The cellular uptake and mitochondrial translocation capacities were similar for all particles, suggesting that differences in aggregation rates during the incorporation of rTPA into MITO-Porter resulted in differences in drug efficacy.

Woven coronary artery (WCA) is a rare anomaly and its etiology remains speculative. Both congenital and acquired factors are considered to be concerned with the pathogenesis. In a 35-year-old man, the tissue characteristics of WCA were evaluated by optical coherence tomography. Serial coronary angiography indicated that acquired factor is the cause, and thrombus recanalization is the most likely pathological mechanism.