Modularized viromimetic polymer nanoparticle vaccines (VPNVaxs) to elicit durable and effective humoral immune responses.

Virus-like particle (VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However, the time-consuming and complicated processes in establishing a current recombinant-protein-based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine (VPNVax), with subunit receptor-binding domain (RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid (PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%-25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

Ferritin-binding and ubiquitination-modified mRNA vaccines induce potent immune responses and protective efficacy against SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) incessantly engenders mutating strains via immune escape mechanisms, substantially escalating the risk of severe acute respiratory syndrome. In this context, the urgent development of innovative and efficacious mRNA vaccines is imperative. In our study, we synthesized six unique mRNA vaccine formulations: the Receptor Binding Domain (RBD) monomer vaccine, RBD dimer (2RBD) vaccine, RBD-Ferritin (RBD-Fe) vaccine, ubiquitin-modified wild-type Nucleocapsid gene (WT-N) vaccine, rearranged Nucleocapsid gene (Re-N) vaccine, and an epitope-based (COVID-19 epitope) vaccine, all encapsulated within the lipid nanoparticle SM102. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that the RBD monomer, RBD dimer (2RBD), and RBD-Fe vaccines elicited robust titers of specific antibodies, including neutralizing antibodies. In contrast, the wild-type N gene (WT-N), rearrange N gene (Re-N), and COVID-19 epitope vaccines predominantly induced potent cellular immune responses. Protective efficacy assays in golden hamsters demonstrated that vaccinated cohorts showed significant reduction in lung pathology, markedly lower viral loads in the lungs, nasal turbinates, and trachea, and substantially reduced transcriptional and expression levels of pro-inflammatory cytokines. Overall, our vaccine candidates pave the way for novel strategies in vaccine development against various infectious agents and establish a critical foundation for the formulation of advanced vaccines targeting emerging pathogens.

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation.

PURPOSE: To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. METHODS: This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. RESULTS: IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. CONCLUSION: Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods.

A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

Study on Related Factors of the Treatment Zone After Wearing Paragon CRT and Euclid Orthokeratology Lenses.

OBJECTIVE: To explore the influence factors of the treatment zone diameter (TZD) and its relationship with axial length growth (ALG) after wearing Paragon CRT and Euclid orthokeratology lenses. METHODS: The right eye data of myopic patients wearing Paragon CRT and Euclid orthokeratology in the ophthalmology department of The First Affiliated Hospital of Soochow University were retrospectively reviewed from April 2019 to October 2022. The TZD and ALG were compared between the Paragon CRT and Euclid groups. The correlation factors of TZD after wearing lens for 1 month and the relationship between the overlapping treatment zone-to-pupil area ratio and the ALG after wearing lens for 1 year were analyzed between the two groups. RESULTS: There were 160 patients (160 eyes) in the Paragon CRT group and 155 patients (155 eyes) in the Euclid group. After wearing lens for 1 month, the TZD in the Paragon CRT group (3.72±0.37 mm) was larger than that in the Euclid group (3.26±0.37 mm) ( P <0.001). The stepwise multivariate linear regression analysis showed that the eccentricity at the flattest meridians (Em) and the central corneal thickness were correlated with the TZD in both groups ( P <0.05). After wearing lens for 1 year, the ALG in the Paragon CRT group (0.32±0.20 mm) was larger than that in the Euclid group (0.25±0.20 mm) ( P =0.001). The stepwise multivariate linear regression analysis showed that the initial wearing age and the overlapping treatment zone area-to-pupil area ratio were correlated with the ALG in both groups ( P <0.05). CONCLUSION: For both the Paragon CRT and Euclid orthokeratology, the wearers with thicker central corneal thickness and smaller Em usually had a smaller TZD. In both groups, the overlapping treatment zone area-to-pupil area ratio was correlated with the ALG.

Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.

Integrating Magnetic-Bead-Based Sample Extraction and Molecular Barcoding for the One-Step Pooled RT-qPCR Assay of Viral Pathogens without Retesting.

Pooling multiple samples prior to real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis has been proposed as a strategy to minimize expenses and boost test throughput during the COVID-19 pandemic. Nevertheless, the traditional pooling approach cannot be effectively deployed in high-prevalence settings due to the need for secondary tests in the case of a positive pool. In this study, we present a pooling test platform with high adaptability and simplicity that allows sample-specific detection of multiple-tagged samples in a single run without the need for retesting. This was accomplished by labeling distinct samples with predefined ID-Primers and identifying tagged pooled samples using one-step RT-PCR followed by melting curve analysis with rationally designed universal fluorescence- and quencher-tagged oligo probes. Using magnetic beads (MBs), nucleic acid targets from different individuals can be tagged and extracted concurrently and then pooled before RT, eliminating the need for extra RNA extraction and separate RT and enzyme digestion steps in the recently developed barcoding strategies. Pools of six samples (positive and negative) were successfully identified by melting temperature values under two fluorescent channels, with a detection sensitivity of 5 copies/µL. We validated the reproducibility of this assay by running it on 40 clinical samples with a hypothetical infection rate of 15%. In addition, to aid the scenario of large-scale pooling tests, we constructed a melting curve autoreadout system (MCARS) for statistical analysis of melting curve plots to eliminate error-prone manual result readout. Our results suggest that this strategy could be a simple and adaptable tool for alleviating existing bottlenecks in diagnostic pooling testing.

Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants.

A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into the inactivated vaccine-induced antibody responses after prime-boost vaccination at both the polyclonal and monoclonal levels. We characterized the VDJ sequence of 118 monoclonal antibodies (mAbs) and found that 20 neutralizing mAbs showed varied potency and breadth against a range of variants including XBB.1.5, BQ.1.1, and BN.1. Bispecific antibodies (bsAbs) based on nonoverlapping mAbs exhibited enhanced neutralizing potency and breadth against the most antibody-evasive strains, such as XBB.1.5, BQ.1.1, and BN.1. The passive transfer of mAbs or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta or Omicron BA.2 variant. The neutralization mechanisms of these antibodies were determined by structural characterization. Overall, a broad spectrum of potent and distinct neutralizing antibodies can be induced in individuals immunized with the SARS-CoV-2 inactivated vaccine BBIBP-CorV, suggesting the application potential of inactivated vaccines and these antibodies for preventing infection by SARS-CoV-2 circulating variants.

Visual field improvement after endoscopic transsphenoidal surgery in patients with pituitary adenoma.

Purpose: To analyze and predict the possibility of visual field (VF) recovery after endoscopic transsphenoidal surgery (ETSS) in patients with pituitary adenoma, we investigated the factors affecting the improvement of the visual field defect (VFD) and built a nomogram predictive model based on these risk factors. We further investigated specific recovery regions of VF associated with the improvement of VFD. Methods: The clinical data of patients who underwent ETSS for pituitary adenomas at a single center between the January 2021 and April 2022 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the predictive factors affecting the improvement in the VF defect and specific recovery regions in patients with pituitary adenomas after ETSS. Results: We enrolled 28 patients (56 eyes) who were hospitalized at our institution. Four clinical features, including compression of the optic chiasm, preoperative mean defect (MD), diffuse defect, and duration of the visual symptom, were chosen from the least absolute shrinkage and selection operator regression analysis to establish the predictive nomogram. The nomogram's area under the curve (AUC) was 0.912, indicating a good degree of differentiation. A calibration plot was used to evaluate the predictive model's calibration, and a decision curve was used to evaluate its clinical application value. The VF defects were improved in the 270-300° range (270-300: RR = 361.00, 95% CI: 21.01-6,202.41). Conclusion: We developed a predictive nomogram model based on significant visual field improvement-associated factors after ETSS in patients with pituitary adenoma. Postoperative visual field improvement is likely to begin at 270-300° in the inferior temporal quadrant. This improvement would enable personalized counselling for individual patients by precisely predicting the visual field recovery after surgery.

Identification of a Novel Interferon Lambda Splice Variant in Chickens.

Type III interferons (IFNLs) have critical roles in the host's innate immune system, also serving as the first line against pathogenic infections of mucosal surfaces. In mammals, several IFNLs have been reported; however, only limited data on the repertoire of IFNLs in avian species is available. Previous studies showed only one member in chicken (chIFNL3). Herein, we identified a novel chicken IFNL for the first time, termed chIFNL3a, which contains 354 bp, and encodes 118 amino acids. The predicted protein is 57.1% amino acid identity with chIFNL. Genetic, evolutionary, and sequence analyses indicated that the new open reading frame (ORF) groups with type III chicken IFNs represent a novel splice variant. Compared to IFNs from different species, the new ORF is clustered within the type III IFNs group. Further study showed that chIFNL3a could activate a panel of IFN-regulated genes and function mediated by the IFNL receptor, and chIFNL3a markedly inhibited the replication of Newcastle disease virus (NDV) and influenza virus in vitro. These data collectively shed light on the repertoire of IFNs in avian species and provide useful information that further elucidate the interaction of the chIFNLs and viral infection of poultry. IMPORTANCE Interferons (IFNs) are critical soluble factors in the immune system, and are composed of 3 types (I, II, and III) that utilize different receptor complexes (IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively). Herein, we identified IFNL from the genomic sequences of chicken and termed it chIFNL3a, located on chromosome 7 of chicken. Phylogenetically clustered with all known types of chicken IFNs, the finding of this IFN is considered a type III IFN. To further evaluate the biological properties of chIFNL3a, the target protein was prepared by the baculovirus expression system (BES), which could markedly inhibit the replication of NDV and influenza viruses. In this study, we uncovered a new interferon lambda splice variant of chicken, termed chIFNL3a, which could inhibit viral replication in cells. Importantly, these novel findings may extend to other viruses, offering a new direction for therapeutic interventions.

Efficient large-scale screening of viral pathogens by fragment length identification of pooled nucleic acid samples (FLIPNAS).

The necessity for the large-scale screening of viral pathogens has been amply demonstrated during the COVID-19 pandemic. During this time, SARS-CoV-2 nucleic acid pooled testing, such as Dorfman-based group testing, was widely adopted in response to the sudden increased demand for detection. However, the current approach still necessitates the individual retesting of positive pools. Here, we established an efficient method termed the fragment-length identification of pooled nucleic acid samples (FLIPNAS), where all subsamples (n = 8) can be uniquely labelled and tested in a single-time detection among pools of samples. We used a novel and simple design of unique primers (UPs) to generate amplicons of unique lengths after reverse transcription and polymerase chain reaction to reach this aim. As a result, the unique lengths of the amplicons can be recognized and traced back to the corresponding UPs and specific samples. Our results demonstrated that FLIPNAS could recognize one to eight positive subsamples in a single test without retesting positive pools. The system also showed sufficient sensitivity for the mass monitoring of SARS-CoV-2 and no cross-reactivity against three common respiratory diseases. Moreover, the FLIPNAS results of 40 samples with a positive ratio of 7.8% were in 100% agreement with their individual detection results using the gold standard. Collectively, this study shows that the efficiency of nucleic acid pooling detection can be further improved by FLIPNAS, which can speed up testing and mitigate the urgent demand for resources.

Correlative factors of ocular surface lesions after allogeneic hematopoietic stem cell transplantation: A retrospective study.

Background: Ocular graft-versus-host disease (oGVHD) is one of the complications after allogeneic hematopoietic stem cell transplantation (HSCT), which impairs the quality of life and may indicate poor prognosis. In this retrospective study, the aim was to investigate the characteristics of ocular surface after HSCT, and analyze the risk factors related to the severity of ocular surface lesions. Methods: 248 post-HSCT patients were enrolled in this retrospective study. Subjects were divided into no lesion group, mild lesion group and severe lesion group, according to the severity of ocular surface lesions. The correlations between grades of ocular surface lesions and gender, age, primary disease, donor source, human leukocyte antigen (HLA) type, kinship, donor-recipient relationship, blood type, source of stem cell and systemic GVHD were analyzed. Results: The median scores of corneal epitheliopathy, lid margin lesions and meibomian gland loss were 3, 6 and 2 points, respectively. The grade of corneal epitheliopathy was related to donor source (P<0.001), kinship (P=0.033), HLA-matching (P<0.001), and systemic GVHD (P=0.007), especially oral GVHD (P<0.001) and liver GVHD (P=0.002). The grade of lid margin lesions was related to donor source (P=0.019), HLA-matching (P=0.006), and systemic GVHD (P=0.013), especially skin GVHD (P=0.019) and oral GVHD (P=0.019). The grade of meibomian gland loss was related to age (P=0.035) and gastrointestinal GVHD (P=0.007). The grade of corneal epitheliopathy after HSCT was related to the lid margin lesion score (P<0.001). Conclusions: The occurrence and development of ocular GVHD are mostly accompanied by the history of systemic GVHD. While in few cases, ocular surface lesions related to GVHD can be observed prior to the rejection of other tissues and organs. Severe corneal epitheliopathy occurs in patients with severe lid margin lesions in ocular GVHD. The lesions of corneal epithelium and lid margin are milder in HLA partially matching transplantation.

How Can Resource-Exhausted Cities Get Out of "The Valley of Death"? An Evaluation Index System and Obstacle Degree Analysis of Green Sustainable Development.

Resource-based cities are suffering from resource scarcity and environmental deterioration. Spirit, vitality and prosperity are disappearing and cities have moved towards "the valley of death" in terms of urban development. This typically appears in environments where it is difficult to maintain sustainable development. Based on empirical analysis, a qualitative analysis method for the selection of evaluation indicators, as well as a quantitative analysis method for index weighting and principal component extraction for constructing a three-level evaluation index system of green development for coal-resource-exhausted cities, was adopted. This study also discussed the life cycle at different development stages of resource-based cities, including mature resource-based and growing resource-based cities. We further argued that the obstacle degree can act as an evaluation basis and make recommendations accordingly to improve the green development of cities. Through star-standard divisions and statistical analysis, it can be explicated that the increase in green development in the first stage is greater than that in the later stage, which is more obvious in cities with lower stars. The results also show the evolution trend and stability coefficient. There is no end in sight for urban green development, and this study can provide a new perspective to relieve the declining trend and promote green sustainable development.

Past-Present-Future: Urban Spatial Succession and Transition of Rail Transit Station Zones in Japan.

In today's environmentally conscious society, advocated by a global point of view, land and building use around rail transit stations have changed in the urbanization process. Promoting urban construction and development centered on rail transit stations not only meets the actual needs of urban sustainable development but is also an important means to guide the development of innovative cities. Therefore, it is meaningful to study the characteristics of urban spatial succession, development rules, and future trends based on this new perspective. We analyzed the relationship between rail transit networks and urban form in Japan using GIS by investigating changes in land and building use around rail transit stations over 30 years in the 1980s, 1990s and 2000s (from 1985-2010) using factor analysis and cluster analysis, and we discussed the impact of land consolidation planning and the setting and site selection of new stations based on urban development to understand the development trends inside and outside station zones and urban spatial succession. The results showed the following: (1) There are certain relationships between the development of urban form and traffic demand, and the rail transit network in Japan has the characteristics of high accessibility and aggregation of a small network; (2) Commercial development with a high plot ratio is dispersed and diverted by high-density rail transit stations in the commercial center of Japan; and (3) Commercial sub-centers form complexes by integrating multi-line transfers and form regional linkages through clustered commercial development. Regional business centers realize the agglomeration and radiation of functions through the compound development of station zones. This case study on rail transit zones and urban spatial succession in Japan has important enlightenment significance for urban construction toward optimizing the location and development of suburban rail transit lines, promoting the compact development of cities, exploring new ways to build more reasonable transport, planning city design and layout for rail transit station zones, and providing decision-making references for urban regeneration and sustainable development.

Corneal perforation associated with ocular graft-versus-host disease.

Corneal perforation is a rare and serious complication of ocular graft-versus-host disease (oGVHD) patients. This study was to retrospectively report seven corneal perforation patients after allogeneic hematopoietic stem cell transplantation (HSCT). Demographic, hematologic, and ophthalmological data of patients were clarified in detail. Nine eyes of seven corneal perforation patients were clarified (Cases 3 and 6 were bilateral and the others are unilateral). All the cases had other affected GVHD organs, especially skin involvement. The duration between HSCT and corneal perforation was usually long with 21 (17-145) months as median interval, whereas the duration between oGVHD diagnosis and corneal perforation was relatively shorter with 4 (2-81) months as median interval. Most patients presented to ophthalmology department with poor visual acuity, BUT and Schirmer's test. Eyelid marginal hyperemia and irregularity were observed in most corneal perforation eyes. Keratoplasty or conjunctival flap covering (CFC) surgeries was performed after corneal perforation. After a long-term follow-up for most patients (median 21 months, range: 2-86 months), only two eyes of two patients (22.22%) had a final BCVA of 20/100 or better. Patients involved in both cutaneous GVHD and blepharitis indicate the aggressive development of oGVHD. Early diagnosis, long-term follow-up, and effective multi-disciplinary treatments for oGVHD patients are essential. Corticosteroids and immunosuppressor remain essential, whereas the use of topical corticosteroids should be carefully considered in corneal ulceration patients. In addition, appropriate surgeries should be performed to control oGVHD development in time.

Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice.

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.

A decoy microrobot that removes SARS-CoV-2 and its variants in wastewater.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can persist in wastewater for several days, has a risk of waterborne-human transmission. The emergence of SARS-CoV-2 variants with increased infection capacity further highlights the need to remove the virus and restrict its spread in wastewater. Here, we report a decoy microrobot created by camouflaging algae with cell membranes displaying angiotensin-converting enzyme 2 (ACE2) for effective elimination of SARS-CoV-2 and its variants. The decoy microrobots show fast self-propulsion (>85 µm/s), allowing for successful "on-the-fly" elimination of SARS-CoV-2 spike proteins and pseudovirus in wastewater. Moreover, relying on the robust binding between ACE2 and SARS-CoV-2 variants, the decoy microrobots exhibit a broad-spectrum elimination of virus with a high efficiency of 95% for the wild-type strain, 92% for the Delta variant, and 93% for the Omicron variant, respectively. Our work presents a simple and safe decoy microrobot aimed toward eliminating viruses and other environmental hazards from wastewater.

Hydrophosphorylation of electron-deficient alkenes and alkynes mediated by convergent paired electrolysis.

A straightforward and practical strategy for hydrophosphorylation of electron-deficient alkenes and alkynes to access γ-ketophosphine oxides, enabled by a convergent paired electrolysis (CPE) in the absence of a metal, base, and redox reagent, has been described. Mechanistic studies have revealed that the diarylphosphane oxides play the dual role of a phosphorus radical precursor and hydrogen donor in this transformation.

Experiment and numerical investigation of inhalable particles and indoor environment with ventilation system.

After the outbreak of COVID-19, the indoor environment has become particularly important in closed spaces, being a common concern in environmental science and public health, and of great significance for the building environment. To improve the indoor air quality and control the spread of viruses, the analysis of inhalable particles in indoor environments is critical. In this research, we study standards focused on inhalable particles and indoor environmental quality, as well as analyzing the movement and diffusion of indoor particles. Based on our analysis, we conduct an experimental study to determine the distribution of indoor inhalable particles of different sizes before and after diffusion under the conditions of underfloor air distribution. Furthermore, the mathematical modeling method is adopted to simulate the indoor flow field, particle trajectories, and pollutant dispersion process. The k-ε two-equation model is applied as the turbulence model in the numerical simulation, while the Lagrangian discrete phase model is adopted to trace the motion of particles and analyze the distribution characteristics of indoor particles. The results demonstrate that fine particles (i.e., those with size less than 0.5 µm) have a significant impact on the indoor particle concentration, while coarse particles (i.e., with size above 2.5 µm) have a greater influence on the total mass concentration of indoor particles. Small-sized particles can easily follow the airflow and diffuse to upper parts of the room. Overall, the effects of indoor particles on indoor air quality, including the potential threat of aerosol transmission of respiratory infectious diseases, are non-negligible. Application of the presented research can contribute to improving the health-related aspects of the building environment.

The global succinylation of SARS-CoV-2-infected host cells reveals drug targets.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.