Direct Construction of 1,4-Dihydropyridazines and Parazoles via Annulation of Alkyl 2-Aroyl-1-chlorocyclopropanecarboxylates.

An efficient and chemodivergent synthesis of highly functionalized 1,4-dihydropyridazines and parazoles has been accomplished via base-promoted annulation between hydrazones and alkyl 2-aroyl-1-chlorocyclopropanecarboxylates, respectively. This transition-metal-free domino reaction proceeded rapidly under mild basic conditions, affording potentially bioactive 1,4-dihydropyridazine and parazole derivatives in moderate yields. The conversion of 1,4-dihydropyridazine to pyrazole was confirmed by adjusting the quantity of the base.

Water scarcity footprint and water saving potential for large-scale green hydrogen generation: Evidence from coal-to-hydrogen substitution in China.

Green hydrogen generated via water electrolysis using photovoltaics or wind has begun to scale up in the process of achieving the global net-zero goal, but there is a lack of research on its impact on the scarcity of water resources and water saving potential. A water resources impact assessment framework for green hydrogen scale-up development is established, integrating the product water footprint and regional water footprint scarcity impacts and advancing the study of the water resources impacts on green hydrogen from water conservation as well as from a sustainable context. The research framework specifies the cradle-to-gate life cycle water consumption of hydrogen production, establishes the water scarcity footprint based on the available water remaining (AWARE) model, quantifies the water saving intensity and potential of the green hydrogen alternative to traditional hydrogen production, and proposes quantitative indicators of the water saving benefit. Taking the regions of 31 provinces in China as a case study, the wind-to­hydrogen scenario and the solar-to­hydrogen scenario will generate approximately 68.86×108 m3 and 126.10×108 m3 water scarcity footprints, respectively. Under the coal-to­hydrogen baseline scenario, approximately 1.68×108 m3 and - 0.57×108 m3 of water saving potential will be generated. In addition, the water saving intensity decreases from west to east. According to the adjusted quantitative indicators of water saving benefits, the wind-to­hydrogen scenario in China can reach 40.22×108 m3eq and the water saving benefit is more obvious in northern regions such as Hebei, Ningxia and Inner Mongolia. The methodological framework can be applied to other countries or regions to assess the sustainable impacts of green hydrogen production on water resources in a given region.

A Hydrogel Dressing Comprised of Silk Fibroin, Ag Nanoparticles, and Reduced Graphene Oxide for NIR Photothermal-Enhanced Antibacterial Efficiency and Skin Regeneration.

Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near-infrared (NIR)-assisted antibacterial therapy. Initially, L-ascorbic acid is used as a reducing agent and PVP-K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self-healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full-thickness bacterial-stained wounds.

SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.

Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.

BaTiO3 Catalyzed Ultrasonic-Driven Piezoelectric-Induced Reversible Addition-Fragmentation Chain-Transfer Polymerization in Aqueous Media.

Compared with normal stimulus such as light and heat, ultrasonic possesses much deeper penetration into tissues and organs and has lower scattering in heterogeneous systems as a noninvasive stimulus. Reversible addition-fragmentation chain-transfer polymerization (RAFT) in aqueous media is performed in a commercial ultrasonic wash bath with 40 kHz frequency ultrasonic, in the presence of piezoelectric tetragonal BaTiO3 (BTO) nanoparticles. Owing to the electron transfer from BTO under the ultrasonic action, the water can be decomposed to produce hydroxyl radical (HO•) and initiate the RAFT polymerization (piezo-RAFT). The piezo-RAFT polymerization exhibits features of controllable and livingness, such as linear increase of molar mass and narrow molar mass distributions (Mw/Mn < 1.20). Excellent temporal control of the polymerization and the chain fidelity of polymers are illustrated by "ON and OFF" experiment and chain extension, separately. Moreover, this ultrasonic-driven piezoelectric-induced RAFT polymerization in aqueous media can be directly used for the preparation of piezoelectric hydrogel which have potential application for stress sensor.

CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients.

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

Resource utilization of MSWI fly ash supporting TiO2/BiOCl nanocomposite for enhanced photocatalytic degradation of sodium isopropyl xanthate: Mechanism and performance evaluation.

The removal of organic pollutants in water environments and the resource utilization of solid waste are two pressing issues around the world. Facing the increasing pollution induced by discharge of mining effluents containing sodium isopropyl xanthate (SIPX), in this work, municipal solid waste incineration fly ash (MSWI FA) was pretreated by hydrothermal method to produce stabilized FA, which was then innovatively used as support for the construction of FA/TiO2/BiOCl nanocomposite (FTB) with promoted photocatalytic activity under visible light and natural sunlight. When the content of FA was 20 wt% and the mass ratio of TiO2 to BiOCl was 4:6, a remarkable performance for the optimal FTB (20-FTB-2) was achieved. Characterizations demonstrated that TiO2 and BiOCl uniformly dispersed on FA contributing to high surface area and broad light adsorption of FTB, which exhibits excellent adsorption capacity and light response ability. Build in electric field formed in the interface of TiO2/BiOCl heterojunction revealed by density functional theory calculations accelerated the separation of photoinduced e- and h+, leading to high efficiency for SIPX degradation. The synergetic effect combined with adsorption and photocatalytic degradation endowed 20-FTB-2 superior SIPX removal efficiency over 99% within 30 min under visible light and natural sunlight irradiation. The photocatalytic degradation pathways of SIPX were determined through theoretical calculations and characterizations, and the toxic byproduct CS2 was effectively eliminated through oxidation of •O2-. For 20-FTB-2, reusability of photocatalyst was showed by cycle tests, also the concentrations of main heavy metals (Pb, Zn, Cu, Cr, and Cd) in the liquid phases released during photocatalyst preparation process (< 1 mg/L) and photodegradation process (< 8.5 µg/L) proved the satisfactory stability with low toxicity. This work proposed a novel strategy to develop efficient and stable support-based photocatalysts by utilizing MSWI FA and realize its resource utilization.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Microalgae Film-Derived Water Evaporation-Induced Electricity Generator with Negative Carbon Emission.

Water evaporation-induced electricity generators (WEGs) are regarded as one of the most promising solutions for addressing the increasingly severe environmental pollution and energy crisis. Owing to the potential carbon emission in the preparation process of WEGs, whether WEG represents a clean electricity generation technology is open to question. Here, a brand-new strategy is proposed for manufacturing negative carbon emission WEG (CWEG). In this strategy, the microalgae film is used as the electricity generation interface of WEG, which achieves a stable open-circuit voltage (Voc) of 0.25 V and a short-circuit current (Isc) of 3.3 µA. Since microalgae can capture carbon dioxide during its growing process, CWEG holds great promise to generate electricity without carbon emissions in the full life cycle compared with other WEGs. To the best of the author's knowledge, this is the first work using microalgae films to fabricate WEG. Therefore, it is believed that this work not only provides a new direction for designing high-efficiency and eco-friendly WEG but also offers an innovative approach to the resource utilization of microalgae.

Artificial intelligence and social media on academic performance and mental well-being: Student perceptions of positive impact in the age of smart learning.

The advancement of artificial intelligence (AI) and the ubiquity of social media have become transformative agents in contemporary educational ecosystems. The spotlight of this inquiry focuses on the nexus between AI and social media usage in relation to academic performance and mental well-being, and the role of smart learning in facilitating these relationships. Using partial least squares-structural equation modeling (PLS-SEM) on a sample of 401 Chinese university students. The study results reveal that both AI and social media have a positive impact on academic performance and mental well-being among university students. Furthermore, smart learning serves as a positive mediating variable, amplifying the beneficial effects of AI and social media on both academic performance and mental well-being. These revelations contribute to the discourse on technology-enhanced education, showing that embracing AI and social media can have a positive impact on student performance and well-being.

Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module.

Plants undergo various age-dependent changes in leaf morphology during the transition from the juvenile to the adult stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a-MdSPL14-MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a-MdSPL14-MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Color-Tunable Organic Light-Emitting Diodes with Single Pt (O

Color-tunable organic light-emitting diodes (CT-OLEDs) have a large color-tuning range, high efficiency and operational stability at practical luminance, making them ideal for human-machine interactive terminals of wearable biomedical devices. However, the device operational lifetime of CT-OLEDs is currently far from reaching practical requirements. To address this problem, a tetradentate Pt(II) complex named tetra-Pt-dbf, which can emit efficiently in both monomer and aggregation states, is designed. This emitter has high Td of 508 °C and large intermolecular bonding energy of -52.0 kcal mol⁻1, which improve its thermal/chemical stability. This unique single-emitter CT-OLED essentially avoids the "color-aging issue" and achieves a large color-tuning span (red to yellowish green) and a high external quantum efficiency （EQE） of ≈30% at 1000 cd m-2 as well as an EQE of above 25% at 10000 cd m-2. A superior LT90 operational lifetime of 520,536 h at a functional luminance of 100 cd m-2, which is over 20 times longer than the state-of-the-art CT-OLEDs, is estimated. To demonstrate the potential application of such OLEDs in wearable biomedical devices, a simple electromyography (EMG)-visualization system is fabricated using the CT-OLEDs.

Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Optimum investment strategy for hydrogen-based steelmaking project coupled with multiple uncertainties.

The large-scale application of hydrogen steelmaking technology is expected to substantially accelerate the decarbonization process of the iron and steel industry. However, hydrogen steelmaking projects are still in the experimental or demonstration stage, and scientific investment decision-making methods are urgently needed to support the large-scale development of the technology. When assessing the investment value, existing studies usually only consider the intrinsic project value under a specific pathway, while ignoring the option value under realistic multiple uncertainties in terms of technology, market, and policy, leading to an underestimation of the investment value. To address this issue, this study constructs a real options model to explore the optimal investment timing and revenue of the hydrogen steelmaking project, by taking into account multi-dimensional uncertainties stemming from price fluctuations in the steel market, the development of the carbon market, and technological advances. Additionally, the impacts of various subsidy policies on the investment strategy are also investigated. Least Squares Monte Carlo method is applied to overcome computational challenges posed by dynamic programming under multi-dimensional uncertainties. The results show that: (i) Investment is not recommended based on current crude steel price and hydrogen price. (ii) When the annual reduction rate of hydrogen price reaches 5%, the optimal investment timing would advance to 2036. (iii) On this basis, with the introduction of a 20% green hydrogen subsidy policy, the optimal investment timing would be further brought forward to 2033. The implementation of tax incentives would significantly increase the investment value. The investment value would surge from 170 million CNY to 262 million CNY as the tax rate decreases from 20% to zero. The findings could provide reasonable suggestions for investment decisions under realistic volatile environments, as well as scientific references for policy design, thus facilitating the large-scale and high-level development of hydrogen-based steelmaking technology.

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Characterization of novel PHEX variants in X-linked hypophosphatemic rickets and genotype-PHEX activity correlation.

BACKGROUND: X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. At present, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully understood. METHODS: In this study, we summarized clinical features in a new cohort of 49 HR patients and detected 16 novel PHEX and 5 novel non-PHEX variants. Subsequently, we studied the pathogenesis of new variants by protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. RESULTS: The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering protein length and localization, whereas truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein in cells. Interestingly, no evident correlation was observed between mutation types and clinical phenotypes. However, when we analyzed the relationship between PHEX activity and serum phosphorus level, we found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Following this observation, we established two new knock-in XLHR mouse models with two novel Phex variants (c.T1349C and c.C426G, respectively) using CRISPR/Cas9 technology. Both mouse models demonstrated clinical manifestations of XLHR seen in patients and PhexC426G mice showed more severe phenotype than PhexT1349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. CONCLUSION: Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study facilitates a better understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation, which is of crucial importance for future diagnosis and treatment of XLHR.

Pharmacokinetic and Safety Study of Bismuth Potassium Citrate Formulations in Healthy Subjects.

BACKGROUND: Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers. OBJECTIVE: To evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects. METHOD: A single-center open two-cycle trial was conducted on 12 healthy subjects who received a single oral dose of 120 mg of bismuth potassium citrate. The plasma concentration of bismuth was determined using a validated inductively coupled plasma mass spectrometry (ICP‒MS) method. The pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the curve concentration-time curve (AUC0-t and AUC0-∞), and safety were evaluated via noncompartment analysis. RESULTS: The ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for Cmax, AUC0-t, and AUC0-∞ were 44.8%, 55.5%, and 64.4%, respectively; the bilateral 95% confidence intervals (Cis) for these parameters were 20.2-99.6%, 24.1-127.5%, and 23.7-175.0%, respectively, and the non-inferior limits for these parameters were 169.4%, 198.8%, and 200.5%, respectively. The upper limits of the one-sided 97.5% confidence interval for the least squares geometric mean ratio (T/R) were lower than the non-inferior limits. No serious adverse reactions or adverse reactions leading to detachment were observed among the subjects. CONCLUSION: The concentration of bismuth in the blood of healthy subjects in the T formulation was not greater than that in the R formulation. Similarly, the safety of oral administration of 120 mg of bismuth potassium citrate formulations to healthy subjects was good. The trial registration number (TRN) was [2018] 013, 6 December 2018.