Corrigendum to "Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors" [Genes Dis 10 (2023) 389-392].

[This corrects the article DOI: 10.1016/j.gendis.2022.07.001.].

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

Nitric Oxide-Releasing Platforms for Treating Cardiovascular Disease.

Cardiovascular disease (CVD) is the first leading cause of death globally. Nitric oxide (NO) is an important signaling molecule that mediates diverse processes in the cardiovascular system, thereby providing a fundamental basis for NO-based therapy of CVD. At present, numerous prodrugs have been developed to release NO in vivo. However, the clinical application of these prodrugs still faces many problems, including the low payloads, burst release, and non-controlled delivery. To address these, various biomaterial-based platforms have been developed as the carriers to deliver NO to the targeted tissues in a controlled and sustained manner. This review aims to summarize recent developments of various therapeutic platforms, engineered to release NO for the treatment of CVD. In addition, two potential strategies to improve the effectiveness of existing NO therapy are also discussed, including the combination of NO-releasing platforms and either hydrogen sulfide-based therapy or stem cell therapy. Hopefully, some NO-releasing platforms may provide important therapeutic benefits for CVD.

Crystal structure of the Ilheus virus helicase: implications for enzyme function and drug design.

BACKGROUND: The Ilheus virus (ILHV) is an encephalitis associated arthropod-borne flavivirus. It was first identified in Ilheus City in the northeast Brazil before spreading to a wider geographic range. No specific vaccines or drugs are currently available for the treatment of ILHV infections. The ILHV helicase, like other flavivirus helicases, possesses 5'-triphosphatase activity. This allows it to perform ATP hydrolysis to generate energy as well as sustain double-stranded RNA's unwinding during ILHV genome replication. Thus, ILHV helicase is an ideal target for inhibitor design. RESULTS: We determined the crystal structure of the ILHV helicase at 1.75-Å resolution. We then conducted molecular docking of ATP-Mn2+ to the ILHV helicase. Comparisons with related flavivirus helicases indicated that both the NTP and the RNA-ILHV helicase binding sites were conserved across intra-genus species. This suggested that ILHV helicase adopts an identical mode in recognizing ATP/Mn2+. However, the P-loop in the active site showed a distinctive conformation; reflecting a different local structural rearrangement. ILHV helicase enzymatic activity was also characterized. This was found to be relatively lower than that of the DENV, ZIKV, MVE, and ALSV helicases. Our structure-guided mutagenesis revealed that R26A, E110A, and Q280A greatly reduced the ATPase activities. Moreover, we docked two small molecule inhibitors of DENV helicase (ST-610 and suramin) to the ILHV helicase and found that these two molecules had the potential to inhibit the activity of ILHV helicase as well. CONCLUSION: High-resolution ILHV helicase structural analysis demonstrates the key amino acids of ATPase activities and could be useful for the design of inhibitors targeting the helicase of ILHV.

Liver injury in COVID-19: A minireview.

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.

Response of activity and community composition of nitrite-oxidizing bacteria to partial substitution of chemical fertilizer by organic fertilizer.

Nitrite oxidation as the second step of nitrification can become the determining step in disturbed soil systems. As a beneficial fertilization practice to maintain high crop yield and soil fertility, partial substitution of chemical fertilizer (CF) by organic fertilizer (OF) may exert a notable disturbance to soil systems. However, how nitrite oxidation responds to different proportions of CF to OF is still unclear. We sampled soils from a 4-year field experiment subject to a gradient of increasing proportions of OF to CF application. Activity, size, and structure of Nitrospira-like and Nitrobacter-like nitrite-oxidizing bacteria (NOB) community were measured. The results revealed that with increasing proportion of OF to CF application, potential nitrite oxidation activity (PNO) showed a marked decreasing trend. PNO was significantly correlated with the abundance of Nitrobacter-like but not Nitrospira-like NOB. The abundance of Nitrobacter-like was significantly influenced by soil organic matter, organic nitrogen (N), and available N. In addition, PNO was also affected by the structure of Nitrobacter-like NOB. The relative abundance of Nitrobacter hamburgensis, alkalicus, winogradskyi, and vulgaris responded differently to the proportions of OF to CF application. Organic N, organic matter, and available N were the main factor shaping their community structure. Overall, Nitrobacter-like NOB is more sensitive and plays a more important role than Nitrospira-like NOB in responding to different proportions of OF to CF application.