Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation.

Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreased N -glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy. Highlights: The interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo.ER-localized GBP5 restricts N-linked glycosylation of SARS-CoV-2 spike protein, leading to protein misfolding and preventing transport to the Golgi apparatus.GBP5 binds to OST complex accessory proteins and potentially blocks access of the catalytic subunit to the spike protein.GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2Pharmacological inhibition of OST blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV. Significance: Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. We found that the interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo. GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2. Importantly, pharmacological inhibition of Oligosaccharyltransferase (OST) Complex blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV, indicating future translational application of our findings.

MSC-derived exosomes deliver ZBTB4 to mediate transcriptional repression of ITIH3 in astrocytes in spinal cord injury.

BACKGROUND: BMSC-secreted exosomes (BMSC-Exos) have shown potential for promoting behavioral recovery following spinal cord injury (SCI). However, its role in blocking astrocyte activation remains unclear. Thus, this study aimed to determine whether BMSC-Exos impair the function of astrocytes following SCI in mice and to seek the mechanism. METHODS: BMSC-Exos were collected by ultracentrifugation and identified. The SCI mice were developed by laminectomy combined with spinal cord shock, followed by BMSC-Exos or nerve growth factor (positive control) treatment. HE staining, Nissl staining, and TUNEL were conducted to analyze the pathological structural damage and neuronal damage in the mouse spinal cord. Bioinformatics was used to screen altered molecules under the BMSC-Exos treatment. Effects of BMSC-Exos and changes in ZBTB4 and ITIH3 expression on neuronal damage induced by activated astrocytes in the co-culture system were analyzed by CCK-8 and flow cytometry. RESULTS: Nerve growth factor and BMSC-Exos promoted motor function recovery, alleviated nerve injury, and reduced apoptosis in mice with SCI. ZBTB4 was enriched in BMSC-Exos and lowly expressed in SCI. Downregulation of ZBTB4 diminished the therapeutic effects of BMSC-Exos against SCI. ITIH3 was a downstream target of ZBTB4. Neurotoxic activation of astrocytes induced neuronal injury, which was alleviated by BMSC-Exos. However, ZBTB4 knockdown overturned the effects of BMSC-Exos in vitro and combined ITIH3 knockdown alleviated the accentuating effects of ZBTB4 knockdown on neuronal injury. CONCLUSION: BMSC-Exos protected against astrocyte-induced neuronal injury by delivering ZBTB4 to repress ITIH3, ultimately improving motor function in mice with SCI.

Manganese Dioxide Coated Piezoelectric Nanosonosensitizer for Cancer Therapy with Tumor Microenvironment Remodeling and Multienzyme-Like Catalysis.

Sonodynamic therapy (SDT) as an emerging method for cancer therapy has encountered difficulty in insufficient production of reactive oxygen species (ROS), especially in tumor microenvironment (TME) with elevated antioxidants and hypoxic conditions. In this work, the authors have fabricated heterostructured manganese dioxide (MnO2)-coated BaTiO3 nanoparticles (BTO@M NPs) as a piezoelectric sonosensitizer, which exhibits the capacity of remodeling TME and multienzyme-like catalysis for boosting SDT. Benefitting from the piezotronic effect, the formation of a p-n junction between MnO2 and piezoelectric BTO with a built-in electric field and band bending efficiently promotes the separation of charge carriers, facilitating the generation of superoxide anion (•O2 -) and hydroxyl radical (•OH) under ultrasound (US) stimulation. Moreover, BTO@M NPs can catalyze the overexpressed hydrogen peroxide (H2O2) in TME to produce oxygen for replenishing the gas source in SDT, and also deplete antioxidant glutathione (GSH), realizing TME remodeling. During this process, the reduced Mn(II) can convert H2O2 into •OH, further amplifying cellular oxidative damage. With these combination effects, the versatile BTO@M NPs exhibit prominent cytotoxicity and tumor growth inhibition against 4T1 breast cancer. This work provides a feasible strategy for constructing high-efficiency sonosensitizers for cancer SDT.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

YOLOH: You Only Look One Hourglass for Real-Time Object Detection.

Multi-scale detection based on Feature Pyramid Networks (FPN) has been a popular approach in object detection to improve accuracy. However, using multi-layer features in the decoder of FPN methods entails performing many convolution operations on high-resolution feature maps, which consumes significant computational resources. In this paper, we propose a novel perspective for FPN in which we directly use fused single-layer features for regression and classification. Our proposed model, You Only Look One Hourglass (YOLOH), fuses multiple feature maps into one feature map in the encoder. We then use dense connections and dilated residual blocks to expand the receptive field of the fused feature map. This output not only contains information from all the feature maps, but also has a multi-scale receptive field for detection. The experimental results on the COCO dataset demonstrate that YOLOH achieves higher accuracy and better run-time performance than established detector baselines, for instance, it achieves an average precision (AP) of 50.2 on a standard 3× training schedule and achieves 40.3 AP at a speed of 32 FPS on the ResNet-50 model. We anticipate that YOLOH can serve as a reference for researchers to design real-time detection in future studies. Our code is available at https://github.com/wsb853529465/YOLOH-main.

Improving the professionalization level of a new generation of construction workers to reduce their unsafe behaviour: an empirical study in China.

Objectives. Improvement of the professionalization level for the new generation of construction workers (NGCWs) is critical to upgrade the construction industry. It also provides a new approach to reduce their unsafe behaviour. The purpose of this study is to analyse the correction mechanism of the professionalization level on NGCWs' unsafe behaviour. We examined the mediating role of work-family conflict and job burnout on impacting NGCWs' unsafe behaviour. The moderation effect of the NGCWs' perceived organizational support was also examined. Methods. The cross-sectional study was conducted based on structural equation modelling, confirmatory factor analysis and regression analysis with a sample of 496 NGCWs in China. Results. The professionalization level can effectively correct NGCWs' unsafe behaviour. Job burnout can independently mediate the relationship between professionalization level and unsafe behaviour and act as a serial mediator for work-family conflict. Moreover, the high level of perceived organizational support will effectively suppress the effect of work-family conflict on job burnout. Conclusions. Improving the professionalization level is an effective way to correct NGCWs' unsafe behaviour. Moreover, management should help the NGCWs balance work and family, to alleviate burnout. Additionally, it is suggested that management should ensure the NGCWs perceive the organizational support.

Chirality of Copper-Amino Acid Nanoparticles Determines Chemodynamic Cancer Therapeutic Outcome.

Chirality is a prevalent characteristic in nature, where biological systems exhibit a significant preference for specific enantiomers of biomolecules. However, there is a limited exploration into utilizing nanomaterials' chirality to modulate their interactions with intracellular substances. In this study, self-assembled copper-cysteine chiral nanoparticles and explore the influence of their charity on cancer chemodynamic therapy (CDT) are fabricated. Experimental and molecular dynamics (MD) simulation results demonstrate that the copper-l-cysteine chiral nanoparticles (Cu-l-Cys NPs) exhibit a stronger affinity toward l-glutathione (l-GSH) that is overproduced in cancer cells, compared to the copper-d-cysteine enantiomer (Cu-d-Cys NPs). The interaction between Cu-l-Cys NPs and l-GSH triggers a redox reaction that depletes l-GSH and converts Cu2+ into Cu+ . Subsequently, Cu+ catalyzes a Fenton-like reaction, decomposing H2 O2 into highly cytotoxic hydroxyl radicals (•OH) for cancer CDT. In vivo, results confirm that Cu-l-Cys NPs with good biocompatibility elicit a pronounced cancer cell death and effectively inhibit tumor growth. This work proposes a new perspective on chirality-enhanced cancer therapy.

Kinetic 18F-FDG PET/CT imaging of hepatocellular carcinoma: a dual input four-compartment model.

BACKGROUND: The endoplasmic reticulum plays an important role in glucose metabolism and has not been explored in the kinetic estimation of hepatocellular carcinoma (HCC) via 18F-fluoro-2-deoxy-D-glucose PET/CT. METHODS: A dual-input four-compartment (4C) model, regarding endoplasmic reticulum was preliminarily used for kinetic estimation to differentiate 28 tumours from background liver tissue from 24 patients with HCC. Moreover, parameter images of the 4C model were generated from one patient with negative findings on conventional metabolic PET/CT. RESULTS: Compared to the dual-input three-compartment (3C) model, the 4C model has better fitting quality, a close transport rate constant (K1) and a dephosphorylation rate constant (k6/k4), and a different removal rate constant (k2) and phosphorylation rate constant (k3) in HCC and background liver tissue. The K1, k2, k3, and hepatic arterial perfusion index (HPI) from the 4C model and k3, HPI, and volume fraction of blood (Vb) from the 3C model were significantly different between HCC and background liver tissues (all P < 0.05). Meanwhile, the 4C model yielded additional kinetic parameters for differentiating HCC. The diagnostic performance of the top ten genes from the most to least common was HPI(4C), Vb(3C), HPI(3C), SUVmax, k5(4C), k3(3C), k2(4C), v(4C), K1(4C) and Vb(4C). Moreover, a patient who showed negative findings on conventional metabolic PET/CT had positive parameter images in the 4C model. CONCLUSIONS: The 4C model with the endoplasmic reticulum performed better than the 3C model and produced additional useful parameters in kinetic estimation for differentiating HCC from background liver tissue.

Copy number gain of FAM131B-AS2 promotes the progression of glioblastoma by mitigating replication stress.

BACKGROUND: Glioblastoma (GBM) is characterized by chromosome 7 copy number gains, notably 7q34, potentially contributing to therapeutic resistance, yet the underlying oncogenes have not been fully characterized. Pertinently, the significance of long noncoding RNAs (lncRNAs) in this context has gained attention, necessitating further exploration. METHODS: FAM131B-AS2 was quantified in GBM samples and cells using qPCR. Overexpression and knockdown of FAM131B-AS2 in GBM cells were used to study its functions in vivo and in vitro. The mechanisms of FAM131B-AS2 were studied using RNA-seq, qPCR, Western blotting, RNA pull-down, coimmunoprecipitation assays, and mass spectrometry analysis. The phenotypic changes that resulted from FAM131B-AS2 variation were evaluated through CCK8 assay, EdU assay, comet assay, and immunofluorescence. RESULTS: Our analysis of 149 primary GBM patients identified FAM131B-AS2, a lncRNA located in the 7q34 region, whose upregulation predicts poor survival. Mechanistically, FAM131B-AS2 is a crucial regulator of the replication stress response, stabilizing RPA1 through recruitment of USP7 and activating the ATR pathway to protect single-stranded DNA from breakage. Furthermore, FAM131B-AS2 overexpression inhibited CD8+ T-cell infiltration, while FAM131B-AS2 inhibition activated the cGAS-STING pathway, increasing lymphocyte infiltration and improving the response to immune checkpoint inhibitors. CONCLUSION: FAM131B-AS2 emerges as a promising indicator for adjuvant therapy response and could also be a viable candidate for combined immunotherapies against GBMs.

Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells.

Neuronal activity can drive progression of high-grade glioma by mediating mitogen production and neuron-glioma synaptic communications. Glioma stem cells (GSC) also play a significant role in progression, therapy resistance, and recurrence in glioma, which implicates potential cross-talk between neuronal activity and GSC biology. Here, we manipulated neuronal activity using chemogenetics in vitro and in vivo to study how it influences GSCs. Neuronal activity supported glioblastoma (GBM) progression and radioresistance through exosome-induced proneural-to-mesenchymal transition (PMT) of GSCs. Molecularly, neuronal activation led to elevated miR-184-3p in neuron-derived exosomes that were taken up by GSCs and reduced the mRNA N6-methyladenosine (m6A) levels by inhibiting RBM15 expression. RBM15 deficiency decreased m6A modification of DLG3 mRNA and subsequently induced GSC PMT by activating the STAT3 pathway. Loss of miR-184-3p in cortical neurons reduced GSC xenograft growth, even when neurons were activated. Levetiracetam, an antiepileptic drug, reduced the neuronal production of miR-184-3p-enriched exosomes, inhibited GSC PMT, and increased radiosensitivity of tumors to prolong survival in xenograft mouse models. Together, these findings indicate that exosomes derived from active neurons promote GBM progression and radioresistance by inducing PMT of GSCs. SIGNIFICANCE: Active neurons secrete exosomes enriched with miR-184-3p that promote glioblastoma progression and radioresistance by driving the proneural-to-mesenchymal transition in glioma stem cells, which can be reversed by antiseizure medication levetiracetam.

Piezoelectric Ba0.85 Sr0.15 TiO3 Nanosonosensitizer with Nitric Oxide Delivery for Boosting Cancer Therapy.

The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (•O2 - ) and hydroxyl radical (•OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.

Self-Driven Electric Field Control of Orbital Electrons in AuPd Alloy Nanoparticles for Cancer Catalytic Therapy.

The free radical generation efficiency of nanozymes in cancer therapy is crucial, but current methods fall short. Alloy nanoparticles (ANs) hold promise for improving catalytic performance due to their inherent electronic effect, but there are limited ways to modulate this effect. Here, a self-driven electric field (E) system utilizing triboelectric nanogenerator (TENG) and AuPd ANs with glucose oxidase (GOx)-like, catalase (CAT)-like, and peroxidase (POD)-like activities is presented to enhance the treatment of 4T1 breast cancer in mice. The E stimulation from TENG enhances the orbital electrons of AuPd ANs, resulting in increased CAT-like, GOx-like, and POD-like activities. Meanwhile, the catalytic cascade reaction of AuPd ANs is further amplified after catalyzing the production of H2 O2 from the GOx-like activities. This leads to 89.5% tumor inhibition after treatment. The self-driven E strategy offers a new way to enhance electronic effects and improve cascade catalytic therapeutic performance of AuPd ANs in cancer therapy.

Hypoxia-Induced Neuronal Activity in Glioma Patients Polarizes Microglia by Potentiating RNA m6A Demethylation.

PURPOSE: Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. EXPERIMENTAL DESIGN: By applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. RESULTS: We demonstrate that hypoxia drove glioma stem cells (GSC) to produce higher levels of glutamate, which activated local neurons. Neuronal activity promoted GBM progression by facilitating microglial M2 polarization through enriching miR-200c-3p in neuron-derived exosomes, which decreased the expression of the m6A writer zinc finger CCCH-type containing 13 (ZC3H13) in microglia, impairing methylation of dual specificity phosphatase 9 (DUSP9) mRNA. Downregulation of DUSP9 promoted ERK pathway activation, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted microglial M2 polarization whereas cortical neuronal inhibition decreased microglial M2 polarization in GBM xenografts. miR-200c-3p knockdown in cortical neurons impaired microglial M2 polarization and GBM xenograft growth, even when cortical neurons were activated. Treatment with the anti-seizure medication levetiracetam impaired neuronal activation and subsequently reduced neuron-mediated microglial M2 polarization. CONCLUSIONS: These findings indicated that hypoxic GSC-induced neuron activation promotes GBM progression by polarizing microglia via the exosomal miR-200c-3p/ZC3H13/DUSP9/p-ERK pathway. Levetiracetam, an antiepileptic drug, blocks the abnormal activation of neurons in GBM and impairs activity-dependent GBM progression. See related commentary by Cui et al., p. 1073.

Unconstrained Piezoelectric Vascular Electronics for Wireless Monitoring of Hemodynamics and Cardiovascular Health.

The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.

Will economic development come at the cost of environmental pollution under fiscal pressure? evidence from resource-based cities in China.

The traditional view is that local governments are inclined to ease environmental regulations in response to fiscal pressure (FP) and alleviate FP by sacrificing the environment for economic development (ED). This paper takes Chinese Mainland resource-based cities (RBC) as the research sample but draws different conclusions. The research results are as follows: firstly, for RBC, although FP reduces environmental pollution (EP), it is not conducive to ED. Compared with non-resource-based cities (NRBC), the economic negative effect of FP in RBC is more obvious. Secondly, FP is detrimental to ED by reducing EP, and RBC have not sacrificed the environment to promote ED in the context of FP. This paper summarizes that the development path of RBC should be "optimizing government behavior → increasing FP → improving environmental quality → reducing ED level." Thirdly, the impact of FP on cities with slower economic growth and smaller economic gap is greater, and the impact of FP on cities with better environment is more obvious. This paper argues that facing FP, RBC in China will not trade EP for ED; at the same time, we suggest RBC in other countries in the face of the FP, not only thinking of promoting ED at the expense of the EP and ease the FP, but also the development of green ecological requirement, overall consideration of the relationship between EP and ED, and then achieve green and sustainable ED without degrading the environment as far as possible.

Plasma cell-free DNA 5-hydroxymethylcytosine and whole-genome sequencing signatures for early detection of esophageal cancer.

Esophageal cancer is a highly incidence and deadly disease with a poor prognosis, especially in developing countries. Owing to the lack of specific symptoms and early diagnostic biomarkers, most patients are diagnosed with advanced disease, leading to a 5-year survival rate of less than 15%. Early (n = 50) and middle-advanced (n = 50) esophageal squamous cell carcinoma (ESCC) patients, as well as 71 healthy individuals, underwent 5-hydroxymethylcytosine (5hmC) sequencing on their plasma cell-free DNA (cfDNA). A Northern Chinese cohort of cfDNA 5hmC dataset of 150 ESCC patients and 183 healthy individuals were downloaded for validation. A diagnostic model was developed using cfDNA 5hmC signatures and then improved by low-pass whole genome sequencing (WGS) features of cfDNA. Conserved cfDNA 5hmC modification motifs were observed in the two independent ESCC cohorts. The diagnostic model with 5hmC features achieved an AUC of 0.810 and 0.862 in the Southern and Northern cohorts, respectively, with sensitivities of 69.3-74.3% and specificities of 82.4-90.7%. The performance was well maintained in Stage I to Stage IV, with accuracy of 70-100%, but low in Stage 0, 33.3%. Low-pass WGS of cfDNA improved the AUC to 0.934 with a sensitivity of 82.4%, a specificity of 88.2%, and an accuracy of 84.3%, particularly significantly in Stage 0, with an accuracy up to 80%. 5hmC and WGS could efficiently differentiate very early ESCC from healthy individuals. These findings imply a non-invasive and convenient method for ESCC detection when clinical treatments are available and may eventually prolong survival.

Comparative analysis of clinical and immunological profiles across Omicron BA.5.2 subvariants using next-generation sequencing in a Chinese cohort.

Objective: The Omicron BA.5.2 variant of SARS-CoV-2 has undergone several evolutionary adaptations, leading to multiple subvariants. Rapid and accurate characterization of these subvariants is essential for effective treatment, particularly in critically ill patients. This study leverages Next-Generation Sequencing (NGS) to elucidate the clinical and immunological features across different Omicron BA.5.2 subvariants. Methods: We enrolled 28 patients infected with the Omicron variant, hospitalized in Zhangjiajie People's Hospital, Hunan, China, between January 20, 2023, and March 31, 2023. Throat swabs were collected upon admission for NGS-based identification of Omicron subvariants. Clinical data, including qSOFA scores and key laboratory tests, were collated. A detailed analysis of lymphocyte subsets was conducted to ascertain the extent of immune cell damage and disease severity. Results: Patients were infected with various Omicron subvariants, including BA.5.2.48, BA.5.2.49, BA.5.2.6, BF.7.14, DY.1, DY.2, DY.3, and DY.4. Despite having 43 identical mutation sites, each subvariant exhibited unique marker mutations. Critically ill patients demonstrated significant depletion in total lymphocyte count, T cells, CD4, CD8, B cells, and NK cells (P < 0.05). However, there were no significant differences in clinical and immunological markers across the subvariants. Conclusion: This study reveals that critically ill patients infected with different Omicron BA.5.2 subvariants experience similar levels of cellular immune dysfunction and inflammatory response. Four mutations - ORF1a:K3353R, ORF1a:L3667F, ORF1b:S997P, S:T883I showed correlation with immunological responses although this conclusion suffers from the small sample size. Our findings underscore the utility of NGS in the comprehensive assessment of infectious diseases, contributing to more effective clinical decision-making.

Comprehensive evaluation of the risk system for heavy metals in the rehabilitated saline-alkali land.

A comprehensive assessment of the heavy metal system in the rehabilitated saline-alkali land holds significant importance, as the in-situ remediation process utilizing amendments substantially alters the initial physicochemical properties of the soil, which could lead to the migration or reactivation of previously stabilized heavy metals. In this context, the present study aims to evaluate the heavy metal content and health risk within the improved saline-alkali soil-plant system. Moreover, a comprehensive evaluation based on the TOPSIS-RSR method is carried out to accurately gauge the soil health status. The findings indicate that the modification process has an impact on the concentrations of heavy metals in the soil and crops, causing either an increase or decrease. However, the level of heavy metal pollution in the improved saline-alkali soil and rape remains within safe limits. The results of the migration of heavy metals after amendment application indicated that the migration of heavy metals in the soil was influenced by the properties of the heavy metals, the composition of the amendment, and leaching. Furthermore, the total non-carcinogenic hazard quotients in the soil and rape were within the safe threshold for all populations. The findings provided novel insights into the status and risk assessment of the pollution of improved saline-alkali soil.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Effective strategies for reclamation of saline-alkali soil and response mechanisms of the soil-plant system.

The combination of amendments has emerged as a potential strategy to efficiently alleviate salt stress in saline-alkali soil. However, knowledge regarding how to optimize the proportion of different amendment materials, comprehensively assess the contribution of each component, and clarify the response mechanisms of the amendment-saline-alkali soil-plant system is incomplete. Based on this, we conducted a pot experiment to evaluate the improvement effect of the combined application of different amendment materials at varying levels and the contribution of the amendment components to alleviating salt stress. Overall, T6 exhibited the most significant improvement effect on the physicochemical and biological properties of the saline-alkali soil and promoted the growth of oilseed rape, with the levels of 2.0 % phosphogypsum, 2.0 % humic acid, 0.25 % bentonite, and 0.03 % sodium carboxymethyl cellulose. Compared with the control group, the EC decreased by 1.51 % to 33.49 %, the soil salt content dropped by 11.40 % to 35.46 %, and the soil soluble Na + concentration significantly declined by 39.47 % to 63.20 %. Additionally, the soil nutrient content and soil microbial community structure were enhanced in treatment groups. Meanwhile, amendments alleviated salt stress in the oilseed rape plant by activating anti-oxidative enzymes and osmoregulatory substances such as soluble sugar and proline, thus improving their ability to remove reactive oxygen species (ROS). The anti-oxidative enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly increased, with an increase of 10.68 % (SOD, T2) ∼207.31 % (CAT, T6) compared to the control group. The structural equation modeling (SEM) analysis and simulation experiments indicated that the amendment components synergically promoted the amelioration effect on salt stress, and effectively improved soil properties, which affected the response of oilseed rape to soil environment. This research paper provides the relevant reference for the combined application of different amendment materials for soil reclamation.