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Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

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Nitrogen-containing organic compounds (NOCs) may potentially contribute to aqueous secondary organic aerosols, yet the different formation of NOCs in aerosol particles and cloud droplets remains unclear. With the in-situ measurements performed at a mountain site (1690 m a.s.l.) in southern China, we investigated the formation of NOCs in the cloud droplets and the cloud-free particles, based on their mixing state information of NOCs-containing particles by single particle mass spectrometry. The relative abundance of NOCs in the cloud-free particles was significantly higher than those in cloud residual (cloud RES) particles. NOCs were highly correlated with carbonyl compounds (including glyoxalate and methylglyoxal) in the cloud-free particles, however, limited correlation was observed for cloud RES particles. Analysis of their mixing state and temporal variations highlights that NOCs was mainly formed from the carbonyl compounds and ammonium in the cloud-free particles, rather than in the cloud RES particles. The results support that the formation of NOCs from carbonyl compounds is facilitated in concentrated solutions in wet aerosols, rather than cloud droplets. In addition, we have identified the transport of biomass burning particles that facilitate the formation of NOCs, and that the observed NOCs is most likely contributed to the light absorption. These findings have implications for the evaluation of NOCs formation and their contribution to light absorption.

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The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%-87%), nitrogen (15%-44%) and phosphorus (26%-43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%-13% while fungi increased by 7.0%-71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, ß-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.

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This article discusses a case study of a 68-year-old male patient with lung squamous cell carcinoma (LUSC) who developed solitary renal metastasis. The importance of routine imaging for detecting asymptomatic renal metastasis is highlighted. The efficacy of various treatment options, including nephrectomy, stereotactic body radiation therapy, and cryoablation, is explored. The study underscores the need for a multidisciplinary team approach in managing LUSC with renal metastasis, due to the lack of clear treatment guidelines.

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Stem cell transplantation has demonstrated efficacy in treating neurological disorders by generating functional cells and secreting beneficial factors. However, challenges remain for current cell suspension injection therapy, including uncontrollable cell distribution, the potential for tumor formation, and limited ability to treat spatial defects. Therefore, implants with programmable cell development, tailored 3D structure, and functionalized biomaterials have the potential to both control cell distribution and reduce or heal spatial defects. Here, a biomimetic material system comprising gelatin, alginate, and fibrinogen has been developed for neural progenitor cell constructs using 3D printing. The resulting constructs exhibit excellent formability, stability, and developmental functions in vitro, as well as biocompatibility and integration into the hippocampus in vivo. The controllability, reproducibility, and material composition of the constructs show potential for use in personalized stem cell-based therapies for defective neurological disorders, neural development research, disease modeling, and organoid-derived intelligent systems.

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Root resource acquisition strategies play a crucial role in understanding plant water uptake and drought adaptation. However, the interrelationships among mycorrhizal associations, root hair development, and fine root strategies, as well as the disparities between C3 and C4 grasses, remain largely unknown. A pot experiment was conducted to determine leaf gas exchange, root morphology, root hair, mycorrhizal fungi, and biomass allocation of three C4 grasses and four C3 grasses, common species of grasslands in Northeast China, under the control and drought conditions. Compared to the C3 grasses, the C4 grasses increased specific surface area by decreasing tissue density, yet exhibited root hair factor at only 21 % of the C3 grasses. Under the drought conditions, the C4 grasses exhibited more intense and extensive adjustments in root traits, characterized by shifts toward a more conservative morphology with increased root diameter and tissue density, as well as reduced mycorrhizal colonization rates. These adaptations led to a decrease in root absorptive function, which was compensated in the C4 grasses by greater root biomass partitioning and root hair factor. Variances in root strategies between plants functional groups were closely related to leaf photosynthetic rate, water and nitrogen use efficiency. We observed that the C4 grasses prefer direct acquisition of soil resources through the fine root pathway over the root hair or mycorrhizal pathway, suggesting a 'do-it-yourself' approach. These findings provide valuable insights into how plant communities of different photosynthetic types might respond to future climate change.

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Background Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging and treatment of nivolumab induced cholangitis.Methods Case reports, case series and clinical studies of nivolumab induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023.Results Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was 7 cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and 7 patients (18.4%) did not improve.Conclusions Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

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BACKGROUND: The rare co-occurrence of oligodendroglioma and arteriovenous malformation (AVM) in the same intracranial location. CASE SUMMARY: In a 61-year-old man presenting with progressive headaches, is described in this case study. Preoperative multimodal imaging techniques (computed tomography, magnetic resonance imaging, magnetic resonance spectroscopy, digital subtraction angiography, and computed tomography angiography) were employed to detect hemorrhage, cystic and solid lesions, and arteriovenous shunting in the right temporal lobe. The patient underwent right temporal craniotomy for lesion removal, and postoperative pathological analysis confirmed the presence of oligodendroglioma (World Health Organization grade II, not otherwise specified) and AVM. CONCLUSION: The preoperative utilization of multimodal imaging examination can help clinicians reduce the likelihood of misdiagnosis or oversight of these conditions, and provides important information for subsequent treatment. This case supports the feasibility of craniotomy for the removal of glioma with AVM.

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In reptiles, such as the red-eared slider turtle ( Trachemys scripta elegans), gonadal sex determination is highly dependent on the environmental temperature during embryonic stages. This complex process, which leads to differentiation into either testes or ovaries, is governed by the finely tuned expression of upstream genes, notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2. Recent studies have identified epigenetic regulation as a crucial factor in testis development, with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T. s. elegans. However, whether KDM6B alone can induce testicular differentiation remains unclear. In this study, we found that overexpression of Kdm6b in T. s. elegans embryos induced the male development pathway, accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C, a temperature typically resulting in female development. Notably, this sex reversal could be entirely rescued by Dmrt1 knockdown. These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway, underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.

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Upregulation of homeoprotein SIX1 in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein SIX1-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of SIX1 mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of SIX1 by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofectamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of SIX1 mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth in vitro. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. In vitro downregulation of SIX1 decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting SIX1, inhibits gastric cancer proliferation and cell growth in vitro, which provides an idea for introducing a new treatment option for gastric cancer.

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Objective: Osteosarcoma (OS) is the most common primary bone sarcoma with a high propensity for local invasion and metastasis. Although the antitumor effect of apatinib has been well confirmed in advanced OS, the synergistic effect of apatinib and immunotherapies has not yet been elucidated. Methods: In this study, we established tumour-bearing mice and observed tumour size with low and high doses of apatinib treatments. The expression of 17 cytokines, including vascular endothelial growth factor (VEGF), was detected by protein microarray analysis. Moreover, we designed apatinib and antigen-specific dendritic cell (DC)-T combination treatment for tumour-bearing mice. Tumour growth was detected by statistical analysis of tumour size and microvessel density (MVD) counting, the protein expression of VEGF by western blotting, the cytokines interleukin 6 (IL-6), IL-17 and interferon-gamma (IFN-γ) by enzyme-linked immunosorbent assay (ELISA), and the numbers of myeloid-derived suppressor cells (MDSCs) and tumour-infiltration macrophages (TAMs) by flow cytometry. Results: The results showed that apatinib efficiently suppressed tumour growth, and high-dose apatinib achieved a stronger effect. The same was true for DC-T immunotherapy. However, their combination treatment revealed a better oncolytic effect. Meanwhile, apatinib or DC-T treatment inhibited the expression of VEGF and the proangiogenic mediators IL-6 and IL-17 but increased IFN-γ production. Combination therapy further reduced/increased these effects. In addition, the combination treatment reduced MDSC but enhanced TAM-M1 ratios in the OS microenvironment. These findings indicated that apatinib and antigen-specific DC-T combination therapy was more efficient in oncolysis by regulating pro-/anti-angiogenic inducers and improving the immune state in the OS microenvironment. Conclusion: This study proved that it was feasible to employ immunotherapy with therapeutic agents in OS treatment, which may provide a new approach in addition to the combination of surgery with chemotherapy in tumour treatment.

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Konjac glucomannan (KGM) molecular chains contain a small amount of acetyl groups and a large number of hydroxyl groups, thereby exhibiting exceptional water retention and gel-forming properties. To meet diverse requirements, KGM undergoes modification processes such as oxidation, acetylation, grafting, and cationization, which reduce its viscosity, enhance its mechanical strength, and improve its water solubility. Researchers have found that KGM and its derivatives can regulate the polarization of macrophages, inducing their transformation into classically activated M1-type macrophages or alternatively activated M2-type macrophages, and even facilitating the interconversion between M1 and M2 phenotypes. Concurrently, the modulation of macrophage polarization states holds significant importance for chronic wound healing, inflammatory bowel disease (IBD), antitumor therapy, tissue engineering scaffolds, oral vaccines, pulmonary delivery, and probiotics. Therefore, KGM has the advantages of both immunomodulatory effects (biological activity) and gel-forming properties (physicochemical properties), giving it significant advantages in a variety of biomedical engineering applications.

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Although diverse microorganisms can remove ammonium and nitrate simultaneously, their metabolic mechanisms are not well understood. Paracoccus denitrificans R-1 showed the maximal NH4 + removal rate 9.94 mg L-1·h-1 and 2.91 mg L-1·h-1 under aerobic and anaerobic conditions, respectively. Analysis of the nitrogen balance calculation and isotope tracing experiment indicated that NH4 + was consumed through assimilation. The maximal NO3 - removal rate of strain R-1 was 18.05 and 19.76 mg L-1·h-1 under aerobic and anaerobic conditions, respectively. The stoichiometric consumption ratio of acetate to nitrate was 0.902 and NO3 - was reduced to N2 for strain R-1 through 15NO3 - isotopic tracing experiment, which indicated a respiratory process coupled with the oxidation of electron donors. Genomic analysis showed that strain R-1 contained genes for ammonium assimilation and denitrification, which effectively promoted each other. These findings provide insights into microbial nitrogen transformation and facilitate the simultaneous removal of NH4 + and NO3 - in a single reactor.

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Primary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain. Therefore, we retrospectively collected 37 PSGT patients who underwent first-line platinum-based chemotherapy from 2010 to 2023. Survival analysis, employing the Kaplan-Meier method, and group comparisons via the log rank test were conducted. Our results show that first-line platinum-based chemotherapy demonstrates favorable efficacy and manageable safety in advanced PSGT, with the combination of Paclitaxel + Platinum emerging as a preferred option.

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The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness-how transplanted cells adapt to new microenvironments and maintain functional stability in vivo-is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

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Background: Our previous research showed that Porphyromonas gingivalis (P. gingivalis) infection can activate the inflammatory signaling pathway and promotes the malignancy development of esophageal squamous cell carcinoma (ESCC). However, the prognostic significance of inflammatory response-related genes (IRRGs) in P. gingivalis-infected ESCC requires further elucidation. Hence, our study constructed a prognostic signature based on P. gingivalis and IRRGs to forecast the survival of patients with ESCC, which may provide insight into new treatment options for ESCC patients. Methods: Differentially expressed genes (DEGs) were identified in P.gingivalis-infected and P.gingivalis-uninfected ESCC cell by RNA sequencing. A risk model was constructed and validated using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database by using univariate Cox regression analysis, LASSO, and the multivariate Cox regression analysis. Kaplan-Meier analysis was carried out to compare the overall survival (OS) between high-risk and low-risk groups. Single-sample gene set enrichment analysis was used to analyze the immune cell infiltration. The Genomics of Drug Sensitivity in Cancer database was used to predict drug sensitivity. Results: There were 365 DEGs between the P.gingivalis-infected and P.gingivalis-uninfected groups. Four genes including DKK1, ESRRB, EREG, and RELN were identified to construct the prognostic risk model (P = .012, C-index = 0.73). In both the training and validation sets, patients had a considerably shorter OS in the high-risk group than those in the low-risk group (P < .05). A nomogram was established using the risk score, gender, and N stage which could effectively forecast the prognosis of patients (P = .016, C-index = 0.66). The high-risk group displayed lower immune infiltrating cells, such as activated dendritic cells, type 2 T helper cells, and neutrophils (P < .05). A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. Conclusion: We demonstrated the potential of a novel signature constructed from 4 P. gingivalis-related IRRGs for prognostic prediction in ESCC patients.

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Purpose: The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students. Methods: Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples. Results: It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach's alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples. Conclusion: The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students.

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Background: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that pose significant challenges in both diagnosis and treatment. The pathogenic mechanism remains unclear, and there is no proteomic analysis-based molecular classification. Therefore, gaining a deeper understanding of this disease from the protein level is crucial because proteins play a fundamental role in the occurrence and development of tumors. Methods: We collected 44 tumor samples from patients diagnosed with HNPGL. The adrenal paraganglioma tissue (N = 46) was used as the disease control group and the chorda tympani nerves (N = 18) were used as the control group. High-pH reversed-phase liquid chromatography and liquid chromatography with tandem mass spectrometry analyses were used to build an integrated protein database of tumor samples. We then obtained two sets of differentially expressed proteins between the tumor group and the control group to identify the unique proteomic signatures of HNPGLs. Ingenuity pathway analysis annotations were used to perform the functional analysis. Subsequently, we developed a clinically relevant molecular classification for HNPGLs that connected the clinical characteristics with meaningful proteins and pathways to explain the varied clinical manifestations. Results: We identified 6,640 proteins in the HNPGL group, and 314 differentially expressed proteins unique to HNPGL were discovered via inter-group comparison. We identified two HNPGL subgroups that significantly differed in clinical manifestation and proteomic characteristics. On the basis of the proteomic results, we proposed a pathogenic mechanism underlying HNPGL. Conclusion: We conducted a comprehensive analysis of the molecular mechanisms of HNPGL to build, for the first time, a clinically relevant molecular classification. By focusing on differential proteomic analyses between different types of paragangliomas, we were able to obtain a comprehensive description of the proteomic characteristics of HNPGL, which will be valuable for the search for significant biomarkers as a new treatment method for HNPGL.

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Owing to the rapid increase of lithium iron phosphate (LiFePO4) batteries, recycling and regeneration of LiFePO4 enjoys significances for sustainable development and environmental protection. In this study, an effective regeneration method for spent LiFePO4 materials and the influence of Al impurity on the electrochemical performance of regenerated LiFePO4 were studied. Firstly, 99.26% Fe, 99.52% P, 99.58% Li, 59.36% Al and 20.24% Cu in spent LiFePO4 material were leached with 150 g•L-1 H2SO4. Subsequently, Al removal and control were achieved by simply adjusting the pH value, and FePO4•2H2O precursors with different Al contents were prepared. Specially, the LiFePO4 regenerated by FePO4•2H2O precursor containing 0.096% Al exhibits excellent electrochemical performance with discharge capacity of 145 mAh•g-1, 140.5 mAh•g-1 and 130.9 mAh•g-1 at the current density of 1C, 2C and 5C, respectively.

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The time-varying effective reproduction number Re(t) is essential for designing and adjusting public health responses. Retrospective analysis of Re(t) helps to evaluate health emergency capabilities. We conducted this study to estimate the Re(t) of the Corona Virus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 Omicron in Shenyang, China. Data on the daily incidence of this Corona Virus Disease 2019 outbreak between March 5, 2022, and April 25, 2022, in Shenyang, China, were downloaded from the Nationwide Notifiable Infectious Diseases Reporting Information System. Infector-infectee pairs were identified through epidemiological investigation. Re(t) was estimated by R-studio Package "EpiEstim" based on Bayesian framework through parameter and nonparametric method, respectively. About 1134 infections were found in this outbreak, with 20 confirmed cases and 1124 asymptomatic infections. Fifty-four infector-infectee pairs were identified and formed a serial interval list, and 15 infector-infectee pairs were included in the generation time table. Re(t) calculated by parameter and nonparametric method all peaked on March 17, 2022, with a value of 2.58 and 2.54 and decreased to <1 after March 28, 2022. There was no statistical difference in the Re(t) distribution calculated using the 2 methods (t = 0.001, P > .05). The present study indicated that the decisive response of Shenyang, China, played a significant role in preventing the spread of the epidemic, and the retrospective analysis provided novel insights into the outbreak response to future public health emergencies.

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