Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China.

OBJECTIVE: This study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer's perspective. METHODS: A Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: According to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost-utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY). CONCLUSIONS: In China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Two-Photon Nanoparticle Probe for Formaldehyde Detection via the AILE Luminescence Mechanism.

A two-photon nanoparticle probe was designed and developed based on the principle of intermolecular interaction of the aggregation-induced locally excited emission luminescence mechanism. The probe has the advantages of simple synthesis, convenient use, strong atomic economy, good biocompatibility, and photobleaching resistance. It can produce a specific and sensitive response to formaldehyde, help detect FA in normal cells and cancer cells, and is expected to become a specific detection probe for FA in vitro and in vivo.

"Ion-imprinting" strategy towards metal sulfide scavenger enables the highly selective capture of radiocesium.

Highly selective capture of radiocesium is an urgent need for environmental radioactive contamination remediation and spent fuel disposal. Herein, a strategy is proposed for construction of "inorganic ion-imprinted adsorbents" with ion recognition-separation capabilities, and a metal sulfide Cs2.33Ga2.33Sn1.67S8·H2O (FJSM-CGTS) with "imprinting effect" on Cs+ is prepared. We show that the K+ activation product of FJSM-CGTS, Cs0.51K1.82Ga2.33Sn1.67S8·H2O (FJMS-KCGTS), can reach adsorption equilibrium for Cs+ within 5 min, with a maximum adsorption capacity of 246.65 mg·g-1. FJMS-KCGTS overcomes the hindrance of Cs+ adsorption by competing ions and realizes highly selective capture of Cs+ in complex environments. It shows successful cleanup for actual 137Cs-liquid-wastes generated during industrial production with removal rates of over 99%. Ion-exchange column filled with FJMS-KCGTS can efficiently treat 540 mL Cs+-containing solutions (31.995 mg·L-1) and generates only 0.12 mL of solid waste, which enables waste solution volume reduction. Single-crystal structural analysis and density functional theory calculations are used to visualize the "ion-imprinting" process and confirm that the "imprinting effect" originates from the spatially confined effect of the framework. This work clearly reveals radiocesium capture mechanism and structure-function relationships that could inspire the development of efficient inorganic adsorbents for selective recognition and separation of key radionuclides.

[Digital twin hospitals: transforming the future of healthcare].

Since the concept of digital twin technology has been put forward, after decades of rapid development and wide application, it has not only made great achievements in many fields, but also brought broader prospects for the development of the medical field. As an important trend in the medical industry, digital twin hospitals play multiple roles by connecting physical hospitals and virtual hospitals and benefit the "patient-medical staff-hospital administrators", highlighting the immeasurable promising application of digital twin technology in smart hospitals. This review takes digital twin technology as an entry point, briefly introduces the progress of its application in various fields, focuses on the characteristics of digital twin technology, practical application cases in hospitals and their limitations, and also looks forward to its future development prospects, aiming to provide certain useful insights and guidance for the future of digital twin hospitals, and also expecting it to play an important role in changing the future of healthcare to a certain extent.

Comparative transcriptome analysis provides insights into the resistance regulation mechanism and inhibitory effect of fungicide phenamacril in Fusarium asiaticum.

Fusarium asiaticum is a destructive phytopathogenic fungus that causes Fusarium head blight of wheat (FHB), leading to serious yield and economic losses to cereal crops worldwide. Our previous studies indicated that target-site mutations (K216R/E, S217P/L, or E420K/G/D) of Type I myosin FaMyo5 conferred high resistance to phenamacril. Here, we first constructed one sensitive strain H1S and three point mutation resistant strains HA, HC and H1R. Then we conducted comparative transcriptome analysis of these F. asiaticum strains after 1 and 10 µg·mL-1 phenamacril treatment. Results indicated that 2135 genes were differentially expressed (DEGs) among the sensitive and resistant strains. The DEGs encoding ammonium transporter MEP1/MEP2, nitrate reductase, copper amine oxidase 1, 4-aminobutyrate aminotransferase, amino-acid permease inda1, succinate-semialdehyde dehydrogenase, 2, 3-dihydroxybenzoic acid decarboxylase, etc., were significantly up-regulated in all the phenamacril-resistant strains. Compared to the control group, a total of 1778 and 2097 DEGs were identified in these strains after 1 and 10 µg·mL-1 phenamacril treatment, respectively. These DEGs involved in 4-aminobutyrate aminotransferase, chitin synthase 1, multiprotein-bridging factor 1, transcriptional regulatory protein pro-1, amino-acid permease inda1, ATP-dependent RNA helicase DED1, acetyl-coenzyme A synthetase, sarcoplasmic/endoplasmic reticulum calcium ATPase 2, etc., showed significantly down-regulated expression in phenamacril-sensitive strain but not in resistant strains after phenamacril treatment. In addition, cyanide hydratase, mating-type protein MAT-1, putative purine nucleoside permease, plasma membrane protein yro2, etc., showed significantly co-down-regulated expression in all the strains after phenamacril treatment. Taken together, This study provides deep insights into the resistance regulation mechanism and the inhibitory effect of fungicide phenamacril and these new annotated proteins or enzymes are worth for the discovery of new fungicide targets.

Knowledge, attitudes, and practice toward tuberculosis in high school students in Qingdao, China.

INTRODUCTION: The purpose of this study is to assess the levels of knowledge, attitude, and practice (KAP) related to TB, and to analyze the differences among various demographic groups. METHODOLOGY: A total of 621 students enrolled in Qingdao High School, coming from high TB burden settings. The cross-sectional study was conducted from May to July of 2022. Participants completed an online questionnaire. Differences in knowledge and practice based on participant characteristics were analyzed using the Wilcoxon rank test and Kruskal-Wallis rank test. Group differences were assessed using a rank-based analysis of variance. RESULTS: The mean percentage of correct answers for TB knowledge and practice was 82.09% and 83.25%, respectively. Grade Three students showed higher knowledge and practice scores than Grade One or Grade Two students (t = -3.9935, p = 0.0002, t = 3.4537, p = 0.0018. 8.58 vs 7.94, 8.58 vs 8.23. t = 3.4562, p = 0.0018, t = -2.8688, p = 0.0128. 1.78 vs 1.61, 1.78 vs 1.64). A significant majority (78.42%) of students expressed fear of being affected by TB. 49.28% of the students would support and help TB patients. 88.08% of participants had heard of TB, with 72.94% learning about it at school, mainly through visual aids like posters. Information was predominantly obtained from online sources (websites, microblogs, WeChat, etc.). CONCLUSIONS: It is recommended to develop a TB curriculum for lower-grade students to enhance awareness of TB prevention through various means, including the internet and social media.

Research progress of post-acute sequelae after SARS-CoV-2 infection.

SARS-CoV-2 has spread rapidly worldwide and infected hundreds of millions of people worldwide. With the increasing number of COVID-19 patients discharged from hospitals, the emergence of its associated complications, sequelae, has become a new global health crisis secondary to acute infection. For the time being, such complications and sequelae are collectively called "Post-acute sequelae after SARS-CoV-2 infection (PASC)", also referred to as "long COVID" syndrome. Similar to the acute infection period of COVID-19, there is also heterogeneity in PASC. This article reviews the various long-term complications and sequelae observed in multiple organ systems caused by COVID-19, pathophysiological mechanisms, diagnosis, and treatment of PASC, aiming to raise awareness of PASC and optimize management strategies.

Enhanced Hydrogen Evolution Catalysis of Pentlandite due to the Increases in Coordination Number and Sulfur Vacancy during Cubic-Hexagonal Phase Transition.

The search for new phases is an important direction in materials science. The phase transition of sulfides results in significant changes in catalytic performance, such as MoS2 and WS2 . Cubic pentlandite [cPn, (Fe, Ni)9 S8 ] can be a functional material in batteries, solar cells, and catalytic fields. However, no report about the material properties of other phases of pentlandite exists. In this study, the unit-cell parameters of a new phase of pentlandite, sulfur-vacancy enriched hexagonal pentlandite (hPn), and the phase boundary between cPn and hPn are determined for the first time. Compared to cPn, the hPn shows a high coordination number, more sulfur vacancies, and high conductivity, which result in significantly higher hydrogen evolution performance of hPn than that of cPn and make the non-nano rock catalyst hPn superior to other most known nanosulfide catalysts. The increase of sulfur vacancies during phase transition provides a new approach to designing functional materials.

Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation.

BACKGROUND: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera. PURPOSE: We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice. METHODS: We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin-eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells. RESULTS: SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

Pregnane X Receptor Activation in Liver Macrophages Protects against Endotoxin-Induced Liver Injury.

Endotoxemia-related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic liver injury remain largely unknown. Here, the expression of PXR is reported in human and murine macrophages, and PXR activation modified immunotypes of macrophages. Moreover, PXR activation significantly attenuated endotoxemic liver injury and promoted macrophage M2 polarization. Macrophage depletion by GdCl3 confirmed the essential of macrophages in the beneficial effects observed with PXR activation. The role of PXR in macrophages is further validated using AAV8-F4/80-Pxr shRNA-treated mice; the PXR-mediated hepatoprotection is impaired, and M2 polarization enhancement is blunted. Additionally, treatment with PXR agonists inhibited lipopolysaccharide (LPS)-induced M1 polarization and favored M2 polarization in BMDM, Raw264.7, and THP-1 cells. Further analyses revealed an interaction between PXR and p-STAT6 in vivo and in vitro. Moreover, blocking Pxr or Stat6 abolished the PXR-induced polarization shift. Collectively, macrophage PXR activation attenuated endotoxin-induced liver injury and regulated macrophage polarization through the STAT6 signaling pathway, which provided a potential therapeutic target for managing endotoxemic liver injury.

All-in-one treatment: Capture and immobilization of 137Cs by ultra-stable inorganic solid acid materials HMMoO6·nH2O (M = Ta, Nb).

Capture and immobilization of 137Cs is urgent for radioactive contamination remediation and spent fuel treatment. Herein, an effective all-in-one treatment method to simultaneously adsorb and immobilize Cs+ without high-temperature treatment is proposed. According to the strategy of incorporating high-valency metal ions into molybdates to increase the material stability and affinity towards radionuclides, layered HMMoO6·nH2O (M = Ta (1), Nb (2)) are prepared. Both materials exhibit excellent acid resistance (even 15 mol/L HNO3). They maintain remarkable adsorption capacity for Cs+ in 1 mol/L HNO3 solutions and can selectively capture Cs+ under excessive competitive ions. Furthermore, they show successful cleanup for actual 137Cs-liquid-wastes generated during industrial production. In particular, adsorbed Cs+ can be firmly immobilized in interlayer spaces of materials due to the highly stable anionic framework. The removal mechanism is attributed to ion exchange between Cs+ and interlayer H+ by multiple characterizations. Study of the structure-function relationship shows that the occurrence of Cs+ ion exchange is closely related to plate-like layered structure. This work develops an efficient all-in-one treatment method for capturing and immobilizing radiocesium by ultra-stable inorganic solid acid materials with low energy consumption and high safety for radionuclide remediation.

Lowering Entropic Barriers in Triplex DNA Switches Facilitating Biomedical Applications at Physiological pH.

Triplex DNA switches are attractive allosteric tools for engineering smart nanodevices, but their poor triplex-forming capacity at physiological conditions limited the practical applications. To address this challenge, we proposed a low-entropy barrier design to facilitate triplex formation by introducing a hairpin duplex linker into the triplex motif, and the resulting triplex switch was termed as CTNSds. Compared to the conventional clamp-like triplex switch, CTNSds increased the triplex-forming ratio from 30 % to 91 % at pH 7.4 and stabilized the triple-helix structure in FBS and cell lysate. CTNSds was also less sensitive to free-energy disturbances, such as lengthening linkers or mismatches in the triple-helix stem. The CTNSds design was utilized to reversibly isolate CTCs from whole blood, achieving high capture efficiencies (>86 %) at pH 7.4 and release efficiencies (>80 %) at pH 8.0. Our approach broadens the potential applications of DNA switches-based switchable nanodevices, showing great promise in biosensing and biomedicine.

A novel alternavirus with three dsRNA segments from Fusarium pseudograminearum, the pathogen of Fusarium crown rot in wheat.

Three dsRNA segments were detected in Fusarium pseudograminearum strain CF14029, a pathogen causing Fusarium crown rot in China. Characterization and sequence analysis confirmed that these dsRNA sequences originated from the same virus. The viral genome consists of three dsRNA segments: dsRNA1 (3,560 nt in length), encoding an RNA-dependent RNA polymerase (RdRp), dsRNA2 (2,544 nt in length), encoding a hypothetical protein, and dsRNA3 (2,478 nt in length), encoding a putative coat protein (CP). Phylogenetic analysis based on the RdRp and CP amino acid sequences revealed a high degree of similarity of this virus to members of the genus Alternavirus, family Alternaviridae, isolated from other Fusarium fungi. As a novel member of the genus Alternavirus, this virus was provisionally named "Fusarium pseudograminearum alternavirus 1" (FpgAV1). Like other alternaviruses found in Fusarium species, the positive-sense strand of each genomic dsRNA of FpgAV1 possesses a poly(A) tail and a distinctive 5'-terminal octamer sequence (5'-GCT GTG TG-3'). This is the first report of the genomic sequence of an alternavirus identified in F. pseudograminearum.

Characterization of Rhizosphere Microbial Diversity and Selection of Plant-Growth-Promoting Bacteria at the Flowering and Fruiting Stages of Rapeseed.

Plant rhizosphere microorganisms play an important role in modulating plant growth and productivity. This study aimed to elucidate the diversity of rhizosphere microorganisms at the flowering and fruiting stages of rapeseed (Brassica napus). Microbial communities in rhizosphere soils were analyzed via high-throughput sequencing of 16S rRNA for bacteria and internal transcribed spacer (ITS) DNA regions for fungi. A total of 401 species of bacteria and 49 species of fungi in the rhizosphere soil samples were found in three different samples. The composition and diversity of rhizosphere microbial communities were significantly different at different stages of rapeseed growth. Plant-growth-promoting rhizobacteria (PGPRs) have been widely applied to improve plant growth, health, and production. Thirty-four and thirty-one PGPR strains were isolated from the rhizosphere soil samples collected at the flowering and fruiting stages of rapeseed, respectively. Different inorganic phosphorus- and silicate-solubilizing and auxin-producing capabilities were found in different strains, in addition to different heavy-metal resistances. This study deepens the understanding of the microbial diversity in the rapeseed rhizosphere and provides a microbial perspective of sustainable rapeseed cultivation.

Efficacy of cyclobutrifluram in controlling Fusarium crown rot of wheat and resistance risk of three Fusarium species to cyclobutrifluram.

Cyclobutrifluram (TYMIRIUM® technology), a new succinate dehydrogenase inhibitor (SDHI) fungicide, is currently being registered by SYNGENTA for controlling Fusarium crown rot (FCR) of wheat in China. The application of 15 or 30 g of active ingredient/100 kg seed of cyclobutrifluram significantly reduced pre-emergence damping-off, discoloration on the stem base and formation of whiteheads caused by FCR. The EC50 values of cyclobutrifluram for 60 isolates of F. pseudograminearum, 30 isolates of F. asiaticum and 30 isolates of F. graminearum ranged from 0.016 to 0.142 mg L-1, 0.010 to 0.041 mg L-1 and 0.012 to 0.059 mg L-1, respectively. One hundred and seven cyclobutrifluram-resistant (CR) mutants were obtained from three Fusarium species isolates, with ten types of mutations identified in Sdh genes. Three Fusarium species isolates exhibited similar resistance mechanisms, with the most prevalent mutations, SdhC1A83V and SdhC1R86K, accounting for 61.68% of mutants. The CR mutants possessed comparable or slightly impaired fitness compared to the corresponding parental isolates. The CR mutants carrying FpSdhBH248Y/Q/D exhibited increased sensitivity to fluopyram. An overall moderate risk of resistance development in three Fusarium species was recommended for cyclobutrifluram.

Genome analyses reveal the secondary metabolites potentially influence the geographical distribution of Fusarium pseudograminearum populations.

Fusarium crown rot (FCR), caused by Fusarium pseudograminearum, significantly impacts wheat yield and quality in China's Huanghuai region. The rapid F. pseudograminearum epidemic and FCR outbreak within a decade remain unexplained. In this study, two high-quality, chromosome-level genomes of F. pseudograminearum strains producing 3-acetyl-deoxynivalenol (3AcDON) and 15-acetyl-deoxynivalenol (15AcDON) toxins were assembled. Additionally, 38 related strains were resequenced. Genomic differences such as single nucleotide polymorphisms (SNPs), insertions/deletions (indels), and structural variations (SVs) among F. pseudograminearum strains were analyzed. The whole-genome SNP locus based population classification mirrored the toxin chemotype (3AcDON and 15AcDON)-based classification, indicating the presence of genes associated with the trichothecene toxin gene cluster. Further analysis of differential SNP, indel, and SV loci between the 3AcDON and 15AcDON populations revealed a predominant connection to secondary metabolite synthesis genes. Notably, the majority of the secondary metabolite biosynthesis gene cluster (SMGC) loci were located in SNP-dense genomic regions, suggesting high mutability and a possible contribution to F. pseudograminearum population structure and environmental adaptability. This study provides insightful perspectives on the distribution and evolution of F. pseudograminearum, and for forecasting the spread of wheat FCR, thereby aiding in the development of preventive measures and control strategies.

Regulatory effect of graphene on growth and carbon/nitrogen metabolism of maize (Zea mays L.).

BACKGROUND: Leakage of graphene into the environment has resulted from its increasing use. Although the impact of graphene on ecosystems is already in full swing, information regarding its impact on plants is lacking. In particular, the effects of graphene on plant growth and development vary, and basic information on the regulation of carbon and nitrogen metabolism is missing. In the current study, the way in which graphene (0, 25, 50, 100, and 200 g kg-1 ) affects maize seedlings was studied in terms of morphological and biochemical indicators. The purpose of this study was to understand better how graphene regulates plant carbon and nitrogen metabolism and to understand its interactions with leaf structure and plant growth. RESULTS: The results showed that 50 g kg-1 graphene increased plant height, stem diameter, leaf area, and dry weight; however, this was inhibited by the high level of graphene (200 g kg-1 ). Further studies indicated that different concentrations of graphene could increase leaf thickness and vascular bundle area as well as the net photosynthetic rate (Pn) of leaves; 25 and 50 g kg-1 graphene enhanced the leaves stomatal conductance (Cond), transpiration rate (Tr), intercellular carbon dioxide (Ci), and chlorophyll content. Higher concentrations decreased the above indicators. At 50 g kg-1 , graphene increased the activity of carbon/nitrogen metabolism enzymes by increasing carbon metabolites (fructose, sucrose, and soluble sugars) and soluble proteins (nitrogen metabolites). These enzymes included sucrose synthase (SS), sucrose phosphate synthase (SPS), nitrate reductase (NR), glutamine synthase (GS), and glutamate synthase (GOGAT). CONCLUSION: These results indicate that graphene can regulate the activities of key enzymes involved in carbon and nitrogen metabolism effectively and supplement nitrogen metabolism through substances produced by carbon metabolism by improving photosynthetic efficiency, thus maintaining the balance between carbon and nitrogen and promoting plant growth and development. The relationship between these indexes explained the mechanism by which graphene supported the growth of maize seedlings by enhancing photosynthetic carbon metabolism and maintaining metabolic balance. For maize seedling growth, graphene treatment with 50 g kg-1 soil is recommended. © 2023 Society of Chemical Industry.

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1-5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT-such as the XBB variant-and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.