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Objective: This research aimed to analyze the prevalence, molecular characteristics, toxinotyping, alpha toxin production potential, and antibiotic resistance pattern of Clostridium perfringens (C. perfringens) isolates in meat samples collected from various sources. Methods: Sixty meat samples were screened for alpha toxin using enzymelinked immunosorbent assay, revealing a positivity rate of 13.3%, predominantly in raw poultry meat. Subsequent culturing on Perfringens agar identified nine samples harboring characteristic C. perfringens colonies, primarily isolated from raw poultry meat. Molecular confirmation through 16S rRNA gene amplification and sequencing authenticated twelve isolates as C. perfringens, with nine strains exhibiting genetic resemblance to locally isolated strains. Toxinotyping assays targeting alpha toxinspecific genes confirmed all nine isolates as type A C. perfringens, with no detection of beta or epsilon toxin genes. Hemolytic assays demonstrated varying alpha toxin production potentials among isolates, with accession number OQ721004.1 displaying the highest production capacity. Moreover, antibiotic resistance profiling revealed multidrug resistance patterns among the isolates. Results: The study identified distinct clusters within C. perfringens strains, indicating variations. Phylogenetic analysis delineated genetic relatedness among strains, elucidating potential evolutionary paths and divergences. Conclusion: The findings underscore the need for robust surveillance and control measures to mitigate the risk of C. perfringens contamination in meat products, particularly in raw poultry meat. Enhanced monitoring and prudent antimicrobial stewardship practices are warranted in both veterinary and clinical settings to address the observed antibiotic resistance profiles and prevent foodborne outbreaks. [ABSTRACT FROM AUTHOR]

The development of the micro-gas sensor for the pressure measurement of the different gas species in the low-pressure domain is an important phenomenon. This paper has investigated the importance of molecular characteristics of the eight different gas species in various pressure domains. Impacts of molecular weight, molecular diameter and viscosity of the selected eight gas species on the induced Knudsen force have been analyzed. This study has employed Direct simulation Monte Carlo (DSMC) results of simulations of the micro-gas sensors for the evaluation of the micro-sensor performance in different gas species. Our investigation shows that the influence of molecular diameter change in the high-pressure domain would result in higher significant Knudsen force change. Knudsen force is also reduced when the value of the gas viscosity is increased. [ABSTRACT FROM AUTHOR]

The components and sources of dissolved organic matter (DOM) in urban water bodies are extremely complicated due to multiple environmental and anthropogenic factors. The comprehensive analysis of the DOM molecular composition is crucial for deep understanding their reactivities, environmental behaviors, and fates in aquatic ecosystems, thereby improving our ability to monitor and protect aquatic systems. In this study, ultraviolet–visible spectroscopy (UV–Vis) and excitation-emission matrix fluorescence spectroscopy (EEM) were combined with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to investigate the optical and molecular characteristics of DOM in the Yongding River (YDH) and Beiyun River (BYH), two typical urban rivers with distinct landscapes and anthropogenic influences in Beijing, China. Results showed that DOM in BYH was mainly composed of proteins from microbial and sewage sources with low aromaticity, molecular weight, and abundant saturated labile compounds, along with a significant presence of anthropogenic surfactants. Whereas the YDH was primarily composed of humic substances from plant- and soil-derived terrestrials, with higher aromaticity humification, unsaturation and refractory compounds. In addition, due to the accumulation of refractory compounds, the concentration of DOC and the degree of organic pollution increased from upstream to downstream of the rivers, manifested as an increase in humification and molecular weight at the molecular level. Our results confirmed that landscape urbanization broadly modified the structure of DOM to be more aliphatic and saturated. The findings of this study will provide important insights into the chemdiverse molecular composition of DOM undergoing different influences from human activities and provide significant guidance for water quality management in urban river ecosystems. Highlights: Distinct molecular composition was observed due to different landscapes and anthropogenic influences. The humification degree, molecular weight, and aromatics of DOM were higher in YDH than BYH. Terrestrial humic materials dominated in YDH, while sewage and microbial-derived proteins dominated in BYH. More anthropogenic surfactants were detected, especially in sewage influenced rivers. [ABSTRACT FROM AUTHOR]

Background: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. Conclusions: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients. [ABSTRACT FROM AUTHOR]

Petrocodon is a small genus in the family Gesneriaceae, which is special for its remarkable floral diversity, and has high ornamental value. In this study, the complete chloroplast genome sequence and genome characteristics of Petrocodon longitubus are first reported. The genome size is 152,958 bp, including a large single-copy region (LSC, 83,901 bp), a small single-copy region (SSC, 18,255 bp), and two inverted repeat sequences (IRs, 25,401 bp, each). The chloroplast genome of P. longitubus was analyzed, revealing a total GC content of 37.47%. A total of 131 genes were de novo assembled, consisting of 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. A comparative analysis was conducted between the chloroplast genome of P. longitubus and three other published species of Petrocodon. The chloroplast genome of four Petrocodon species was found to have a double-chain ring structure, with a size ranging from 152,958 to 153,292 bp. Chloroplast genome size had indistinguishable. Four Petrocodon species was ra elatively conserved sequence, with 87 or 88 protein-coding genes, and 8 rRNA were the most conserved, which contains 42 ~ 50 SSR sites, which are mainly mononucleotides and dinucleotides, 4 boundary transition regions, then trinucleotides, pentanucleotides and hexanucleotides have been not detected. The non-preferred codons of the chloroplast genome in the four Petrocodon species are those ending in A, C, G, or T. The chloroplast genomes of these four Petrocodon species are highly similar to each other and to several Primulina species. Phylogenetic trees indicate that P. longitubus and other Petrocodon species were grouped together in a clade, with P. longitubus form a single clade. The results support the scientific naming of P. Longitubusr based on horticultural traits and further clarify the systematic status using molecular information. [ABSTRACT FROM AUTHOR]

Purpose: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. Methods: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. Results and conclusions: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK–RAS–MAPK, TP53, and WNT. Notably, the RTK–RAS–MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK–RAS–MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients. [ABSTRACT FROM AUTHOR]

Abstract The components and sources of dissolved organic matter (DOM) in urban water bodies are extremely complicated due to multiple environmental and anthropogenic factors. The comprehensive analysis of the DOM molecular composition is crucial for deep understanding their reactivities, environmental behaviors, and fates in aquatic ecosystems, thereby improving our ability to monitor and protect aquatic systems. In this study, ultraviolet–visible spectroscopy (UV–Vis) and excitation-emission matrix fluorescence spectroscopy (EEM) were combined with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to investigate the optical and molecular characteristics of DOM in the Yongding River (YDH) and Beiyun River (BYH), two typical urban rivers with distinct landscapes and anthropogenic influences in Beijing, China. Results showed that DOM in BYH was mainly composed of proteins from microbial and sewage sources with low aromaticity, molecular weight, and abundant saturated labile compounds, along with a significant presence of anthropogenic surfactants. Whereas the YDH was primarily composed of humic substances from plant- and soil-derived terrestrials, with higher aromaticity humification, unsaturation and refractory compounds. In addition, due to the accumulation of refractory compounds, the concentration of DOC and the degree of organic pollution increased from upstream to downstream of the rivers, manifested as an increase in humification and molecular weight at the molecular level. Our results confirmed that landscape urbanization broadly modified the structure of DOM to be more aliphatic and saturated. The findings of this study will provide important insights into the chemdiverse molecular composition of DOM undergoing different influences from human activities and provide significant guidance for water quality management in urban river ecosystems. Graphical Abstract

Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

ObjectiveTo provide scientific basis for the prevention and control of foodborne diseases and clinical treatment， the serological， drug resistance and molecular typing characteristics of Salmonella isolated from patients with foodborne diarrhea in Wenzhou City was investigated.MethodsA total of 567 Salmonella strains isolated from foodborne diarrhea cases in Wenzhou City from 2017 to 2021 were sorted out and serotyped. The susceptibility tests to 15 antimicrobial agents were performed using the broth microdilution method. Pulsed field gel electrophoresis （PFGE） was used for molecular typing.ResultsAmong the 567 patients of Salmonella， 326 were male and 241 were female， accounting for 57.5% and 42.5%， respectively. Most of them were children under 6 years old， and 119 strains were isolated， accounting for 21.0%. Next was the elderly over 60 years old， 111 strains of Salmonella were isolated， accounting for 19.6%. The 567 isolates of Salmonella were divided into 50 serotypes， among which the top two serotypes were Salmonella typhimurium （33.5%， 190/567） and Salmonella enteritidis （23.6%， 134/567）. The results showed that the resistance rate to ampicillin was the highest （73.5%， 417/567）. It was followed by tetracycline （63.3%， 359/567）. Salmonella typhimurium had the highest resistance to tetracycline （84.2%， 160/190）， and Salmonella enteritidis had the highest resistance to nalidixic acid （95.5%， 128/134） among 15 antibiotics. Among 567 strains of Salmonella， 178 kinds of drug resistance spectrum were found， the rate of multiple drug resistance was 62.6%and the highest proportion was AMP-AMS-CFZ-CT-NAL. The 201 strains of Salmonella typhimurium and the monophasic varieties of Salmonella typhimurium produced 70 band types. The band types varied greatly and the similarity was between 1.5% and 100%. One hundred and twenty-seven strains of Salmonella enteritidis obtained a total of 32 band types with the similarity between 35.8% and 100%. Fifty strains of Salmonella london obtained a total of 24 band types by PFGE， and the similarity was between 40.0% and 100%.ConclusionFoodborne Salmonella strains isolated in Wenzhou displayed diverse serotypes， varying degrees of drug resistance， and multi-drug resistance. To effectively prevent and control foodborne diseases caused by Salmonella， enhancing monitoring of Salmonella among foodborne diarrhea patients was essential. Timely understanding of Salmonella serotype distribution trends and drug resistance patterns in the region， followed by appropriate measures， was imperative.

Abstract Background Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored. Methods Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). Results In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p

Abstract Background Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. Methods Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. Results RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). Conclusions The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Background: Vibrio vulnificus (V. vulnificus) is a deadly opportunistic human pathogen with high mortality worldwide. Notably, climate warming is likely to expand its geographical range and increase the infection risk for individuals in coastal regions. However, due to the absence of comprehensive surveillance systems, the emergence and characteristics of clinical V. vulnificus isolates remain poorly understood in China. Methods: In this study, we investigate antibiotic resistance, virulence including serum resistance, and hemolytic ability, as well as molecular characteristics of 21 V. vulnificus isolates collected from patients in Ningbo, China. Results and discussion: The results indicate that all isolates have been identified as potential virulent vcg C type, with the majority (16 of 21) classified as 16S rRNA B type. Furthermore, these isolates exhibit a high level of antibiotic resistance, with 66.7% resistance to more than three antibiotics and 61.9% possessing a multiple antibiotic resistance (MAR) index exceeding 0.2. In terms of virulence, most isolates were categorized as grade 1 in serum resistance, with one strain, S12, demonstrating intermediate sensitivity in serum resistance, belonging to grade 3. Whole genome analysis disclosed the profiles of antibiotic resistance genes (ARGs) and virulence factors (VFs) in these strains. The strains share substantial VF genes associated with adherence, iron uptake, antiphagocytosis, toxin, and motility. In particular, key VFs such as capsule (CPS), lipopolysaccharide (LPS), and multifunctional autoprocessing repeats-in-toxin (MARTX) are prevalent in all isolates. Specifically, S12 possesses a notably high number of VF genes (672), which potentially explains its higher virulence. Additionally, these strains shared six ARGs, namely, PBP3, adeF, varG, parE, and CRP, which likely determine their antibiotic resistance phenotype. Conclusion: Overall, our study provides valuable baseline information for clinical tracking, prevention, control, and treatment of V. vulnificus infections. [ABSTRACT FROM AUTHOR]

We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3–189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3–54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST. • OYST tumor histology and residual lesions were independently associated with event free survival. • OYST histology, residual lesions and cycles to AFP normalization were independent risk factors for OYST overall survival. • Persistent and recurrent OYST demonstrated distinct molecular characteristics compared with primary OYST. • Persistent and recurrent OYST probably susceptible to immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

Background: Early-onset colorectal cancer (EOCRC) is associated with a poorer prognosis relative to late-onset colorectal cancer (LOCRC), and its incidence has witnessed a gradual escalation in recent years. This necessitates a comprehensive examination of the underlying pathogenesis and the identification of therapeutic targets specific to EOCRC patients. The present study aimed to delineate the distinct molecular landscape of EOCRC by juxtaposing it with that of LOCRC. Methods: A total of 11 344 colorectal cancer patients, diagnosed between 2003 and 2022, were enrolled in this study, comprising 578 EOCRC cases and 10 766 LOCRC cases. Next-generation sequencing technology was employed to assess the tumor-related mutation and tumor mutation burden (TMB) in these patients. PD-L1 expression was quantified using immunohistochemistry. Microsatellite instability (MSI) was determined via capillary electrophoresis (2B3D NCI Panel). Results: Upon comparing LOCRC with EOCRC patients, the latter group demonstrated a tendency towards advanced TNM stage, lower tumor differentiation, and less favorable histological types. Among LOCRC patients, those with MSI-H status were found to have an earlier TNM stage compared to those with MSI-L/MSS status. Significantly, the incidence of MSI-H was notably higher in EOCRC (10.2%) compared to LOCRC (2.2%). Mutations in the 7-gene panel (ARID1A, FANCI, CASP8, DGFRA, DPYD, TSHR, and PRKCI) were more prevalent in LOCRC. Within the EOCRC cohort, patients with the MSI-H subtype displayed an earlier TNM stage but concurrently exhibited poorer tissue differentiation and a higher frequency of mucinous adenocarcinoma. Among EOCRC patients, FBXW7, FAT1, ATM, ARID1A, and KMT2B mutations were significantly enriched in the MSI-H subgroup. A comparative analysis of MSI-H patients revealed heightened mutation frequencies of FGFBR2, PBRM1, RNF43, LRP1B, FBXW7, ATM, and ARID1A in the EOCRC group. Furthermore, EOCRC patients demonstrated a higher overall TMB, particularly in the MSI-H subtype. PD-L1 expression was elevated in EOCRC and positively associated with MSI status. Conclusions: This study revealed a significantly higher MSI-H distribution rate in EOCRC, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored. Methods: Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). Results: In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p < 0.0001) in the TCGA cohort, suggesting that EGFR fusion might be a high-risk factor for poor prognosis. Conclusions: Our study is the first retrospective analysis of EGFR fusions in a large-scale solid tumor population, which may provide a reference for future EGFR-TKI clinical trials with EGFR fusions. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs. [ABSTRACT FROM AUTHOR]

Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China’s poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019- 014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4. [ABSTRACT FROM AUTHOR]

Objective To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜ 0.05). Conclusions Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement. [ABSTRACT FROM AUTHOR]

In this study, we aimed to describe the morphological and molecular characteristics of Austroglycyphagus geniculatus (Acari: Glycyphagidae) breeding in fodder. Flour and corn-crushed fodder samples were collected from a small fodder processing mill in Wuhu, Anhui province, China. The detection rate of A. geniculatus was 100% in six samples, and the breeding density was 1.44 mites/g. Under an optical microscope, we observed that the mite body was oval and small in size. The epidermis of the mite was coated with fine particles. We found two obvious, large, and red lateral ventral glands on either side of hysterosoma. The gene sequences for internal transcribed spacer (ITS) and mitochondrial cytochrome oxidase 1 (COX 1) of A. geniculatus were amplified and uploaded to the GenBank nucleotide sequence database. To the best of our knowledge, this is the first study to report the detailed description of the morphological and molecular characteristics of A. geniculatus. The results of phylogenetic relationships obtained from the ITS and COX 1 support the classification statuses of A. geniculatus to the family Glycyphagidae based on the morphological classification. Our study provides morphological and molecular data for inferring phylogenetic relationship of A. geniculatus. [ABSTRACT FROM AUTHOR]

[Objective] The present paper aimed to explore the role of AcinJHBP gene in the growth, development and diapause of Apocheima cinerarius. [Method] Based on the transcriptome data (non-diapause pupa/diapause pupa and diapause pupa/diapause depupa), JHBP gene was cloned and named as AcinJHBP (GenBank entry number: OR860357). The sequence and physicochemical properties of AcinJHBP gene were analyzed by bioinformatics software. The temporal and spatial expression of Acin JHBP (different developmental stages and tissues) was detected by qPCR. [Result] The complete CDS sequence of Acin JHBP gene of A. cinerarius was 726 bp, encoding 241 amino acids, the predicted molecular weight of protein was 26.97 kDa, and the predicted isoelectric point was 5. 13. The predicted molecular formula of Acin JHBP gene was C121 H1915 N313 0364 S9, the total charge of negative charge residues (Asp + Glu) was 34, the total charge of positive charge residues (Arg + Lys) was 26, the half-life and aliphatic index were 30 hours and 97.51, respectively. The average hydrophilicity of the protein was 0.098, and the predicted instability coefficient was 27. 13. Therefore, the protein was a hydrophilic stable protein, and the N-terminal amino acid was methionine (Met, M). AcinJHBP contained a signal peptide of 17 amino acid residues at the N-terminus, but had no transmembrane region. Phosphoric acid sites were found in serine, threonine and tyrosine phosphate sites were 9,6 and 3, respectively, and no glycosylation sites were found. Subcellular localization results showed that it was mainly located outside the cell. Phylogenetic analysis showed that AcinJHBP had the closest relationship with the hemolymph juvenile hormone binding protein JHBP of Operophtera brumata. The results of gene expression showed that the expression of Acin JHBP was lower at different developmental stages (except the 3rd instar larvae), and there was no significant difference between the egg and the 5th instar larvae (P>0.05), for all that the expression of Acin JHBP showed a decreasing trend in non-diapause pupa-adult stage. In different tissues, the expression of AcinJHBP gene was the highest in the male head of A. cinerarius. [Conclusion] Acin JHBP gene is closely related to the growth, development and diapause of A. cinerarius. The results lay a theoretical foundation for further revealing the function of the gene in the summer and winter diapause of the pupae in A. cinerarius. [ABSTRACT FROM AUTHOR]

The vibrating superfine mill (VSM) is a machine that belongs to the micronization technique. In this study, VSM was employed to produce micronized tapioca starch by varying micronization times (15, 30, 45, and 60 min). The structural and physicochemical properties of the micronized starch were then examined. Scanning electron microscopy studies revealed that micronized starch was partially gelatinized, and the granule size dramatically increased when micronization time increased. X‐ray diffraction patterns showed that the relative crystallinity was decreased from 24.67% (native) to 4.13% after micronization treatment for 15 min and slightly decreased after that. The solubility of micronized starch significantly increased as the micronization time increased, which was associated with the destruction of the starch crystalline structure. Differential scanning calorimetry investigations confirmed that micronized starch was "partly gelatinized," and the degree of gelatinization increased to 81.27% when the micronization time was 60 min. The weight‐average molar mass was reduced by 15.0% (15 min), 30.9% (30 min), 55.7% (45 min), and 70.5% (60 min), respectively, indicating that the molecular structure was seriously degraded. The results demonstrated that the physicochemical changes of micronized starch granules were related to the destruction of the starch structure. These observations would provide details on micronized starch and its potential applications. Practical Application: These observations would provide details on micronized starch and its potential applications. Moreover, we believe that when the structures of starches were known, it is probable that the effect of VSM on the structural and physicochemical properties change of other starches might be predicted by adjusting the processing time. [ABSTRACT FROM AUTHOR]

Abstract Background Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known. Methods The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection. Results Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was −4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected. Conclusions Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated. Graphical Abstract

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

Zhangrui Zeng,1,&ast; Yueshuai Wei,1,&ast; Caihong Ye,1 Yuan Jiang,1 Chunlin Feng,1 Tongtong Guo,1 Min Song,1 Yinhuan Ding,1 Ping Zhan,2 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 2Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China, Te/Fax +86 0830 3165730, Email liujb7203@swmu.edu.cnPurpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections.Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections.Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors.Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.Keywords: carbapenem-resistant, Enterobacter cloacae complex, antimicrobial resistance, molecular characteristics, risk factors

Abstract Background Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

Biomass burning serves as important sources of volatile organic compounds (VOCs), yet our understanding of the molecular characteristics of oxygenated volatile organic compounds (OVOCs) from fresh emissions remains limited. In this study, gaseous organic compounds in fresh smokes from burning typical Chinese crop straws and woods are measured using an iodide time‐of‐flight chemical ionization mass spectrometer. Approximately 750 molecular formulas are identified, with CHO compounds containing carbon, hydrogen and oxygen atoms accounting for 77%–95% of the total. C1–C3 organic acids and dicarboxylic acids dominate the total CHO signal intensities by 27%–48%, while well‐known molecular markers of biomass burning, such as monosaccharide, guaiacol and syringol derivatives, contribute 7%–17%. Notably, crop straw and wood burning emit a higher abundance of guaiacol than syringol derivatives by a factor of 5. Additionally, a variety of nitrogen‐containing compounds (mainly in the CHON group) is identified, including isocyanate, amide, amino acids, and pyridine. The mass spectral profiles of organic compounds are largely similar between crop straw and wood burning fuels, although wood burning produces higher contributions of compounds with carbon atoms numbers >10. The saturation concentrations of organic compounds are estimated using molecular formula‐based volatility parameterization, revealing that semi‐volatile and intermediate VOCs (S/intermediate volatility organic compounds (IVOCs)) predominate smoke releases by 35%–60% and 20%–43%, respectively, with only a small fraction of low‐volatility compounds. Given the widespread nature of biomass burning in winter China, our results may have significant implications for interpreting secondary organic aerosol formation through gas‐particle partitioning or aqueous‐phase reactions. Plain Language Summary: Biomass burning is a significant source of volatile organic compounds (VOCs), with oxygenated volatile organic compounds (OVOCs) being particularly important due to their high reactivity and their contribution to the radical budget and secondary products formation. However, previous research has primarily focused on a limited number of OVOCs species from pine, spruce, and other biofuels, leading to insufficient studies on the full mass spectra of OVOCs from biomass smokes. Our study has addressed this gap by identifying approximately 750 OVOCs from burning typical Chinese crop straws and woods. We found that C1–C3 organic acids and dicarboxylic acids are the predominant contributors to total signal intensities. This expands on previous studies that have focused on a limited well‐known molecular markers of biomass burning, such as monosaccharide, guaiacol and syringol derivatives, and reveals the presence of nitrogen‐containing compounds, including isocyanate, amide, amino acids, and pyridine. The saturation concentrations of organic compounds are estimated, highlighting the importance of semi‐volatile and intermediate VOCs (S/IVOCs) in fresh smoke releases. Our study contributes to a better understanding of complex chemistry of biomass burning and its impact on air quality. It will serve as a crucial basis for accurately assessing biomass burning related‐secondary organic aerosol formation. Key Points: C1–C3 organic acids and dicarboxylic acids dominate the total signal intensities of fresh crop straw and wood burning emissionsThe mass spectral profiles are largely similar across different fuels, with wood burning produces higher contributions of large compoundsSemi‐volatile and intermediate volatile organic compounds predominate fresh smoke emissions, with only a small fraction of low‐volatility compounds [ABSTRACT FROM AUTHOR]

Background: Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes. Methods: We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC. Results: In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in KRAS (OR, 95% CI: 0.91, 0.85-0.98), BRAF (0.63, 0.51-0.78), APC (0.70, 0.58-0.84), and NRAS (0.88, 0.78-1.00) but more likely to include mutations in PTEN (1.68, 1.04-2.73) and TP53 (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and BRAF (0.77, 0.64-0.92) and APC mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with PIK3CA mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent. Discussion: A lower prevalence of mutations in KRAS and BRAF is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and TP53 and PTEN mutations, which may serve as therapeutic targets. [ABSTRACT FROM AUTHOR]

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application. [ABSTRACT FROM AUTHOR]

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Background: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis. [ABSTRACT FROM AUTHOR]

Background: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. Methods: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co‐mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. Results: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI‐positive and one was MVI‐negative, and there was a co‐occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease‐free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p‐values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). Conclusions: TERTp+/TP53+ was significantly enriched in MVI‐positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI‐positive patients and poor prognosis, laying a preliminary foundation for further exploration of co‐mutation in HCC with MVI and clinical treatment. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy. [ABSTRACT FROM AUTHOR]

To study the O174L gene of African swine fever virus (ASFV), the O174L gene was connected to the vector pRK5M-C-2xStrep through homologous recombination, and the eukaryotic expression vector of ASFV was constructed. After PCR amplification and sequencing identification, the recombinant plasmid was transfected into porcine intestinal epithelial cells (IPEC-J2). The expression of O174L protein was detected by immunofluorescence and Western blot. The PCR and sequencing results showed that recombinant plasmid pRK5M-C-2xStrep-O174L was successfully constructed. The results of immunofluorescence and Western blot showed that O174L protein could be stably expressed in IPEC-J2 cells. Bioinformatics analysis of O174L protein showed that the arrangement of the branches and isolates of the phylogenetic tree based on the O174L gene sequence was highly similar to that based on the B646L (p72) gene sequence. Among the 16 isolates from China, the similarity of the O174L gene sequence between the isolates was as high as 96.76%~100.00%. Compared with other type II isolates in China, China/2018/AnhuiXCGQ had differences in the 67th, 75th and 110th amino acids of O174L, and GZ201801 had difference in the 110th amino acids. The O174L amino acid sequence of type ? isolates SD/DY-I/2021 and HeN/ZZ-P1/2021 were different from other Chinese type II isolates at 13th, 73th, 93th, 95th, 113th and 114th amino acids, respectively. O174L protein was a stable hydrophilic protein without signal peptide and transmembrane region. The secondary structure of O174L protein was composed of a helix, β strand and random coil, and the prediction result of tertiary structure was consistent with the secondary structure. Above results provided the basis and experimental materials for studying the protein interaction and genetic evolution between ASFV and host. [ABSTRACT FROM AUTHOR]

As an immunosuppressive disease virus, chicken infectious anemia virus (CIAV) mainly infects chickens, causing aplastic anemia and systemic lymphoid tissue atrophy. In recent years, the prevalence of CIAV in the poultry industry globally has caused huge economic losses. In this study, a total of 223 clinical samples, including anal swabs, tissues, blood, and vaccines, were collected from 19 broiler farms or breeding companies in Jiangsu province, with symptoms of significant anemia and immunosuppression during 2020-2022. Among them, 75 samples (75/223, 33.6%) were positive for CIAV in polymerase chain reaction (PCR) test, and 20 CIAV strains were successfully isolated. The phylogenetic trees of the 20 isolates and 42 CIAV strains deposited in GenBank formed four distinct groups (A-D). And the isolates mainly belonged to Group A but with high genetic diversity. Analysis for VP1 indicated that these isolates possess key characteristics of highly pathogenic strains. Meanwhile, VP2 and VP3 were much conserved with much fewer mutations compare to VP1. The above epidemiological study of CIAV provides novel insights into molecular characterization of CIAV and lays the foundation for developing efficient strategies for control of CIAV in China. [ABSTRACT FROM AUTHOR]

Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of PoRVA in the world, including China, is of significance for disease prevention. In 2022, a total of 25,768 samples were collected from 230 farms across China, undergoing porcine RVA positivity testing. The results showed that 86.52% of the pig farms tested positive for porcine RVA, with an overall positive rate of 51.15%. Through the genetic evolution analysis of VP7, VP4 and VP6 genes, it was revealed that G9 is the predominant genotype within the VP7 segment, constituting 56.55%. VP4 genotypes were identified as P[13] (42.22%), P[23] (25.56%) and P[7] (22.22%). VP6 exhibited only two genotypes, namely I5 (88.81%) and I1 (11.19%). The prevailing genotype combination for RVA was determined as G9P[23]I5. Additionally, some RVA strains demonstrated significant homology between VP7, VP4 and VP6 genes and human RV strains, indicating the potential for human RV infection in pigs. Based on complete genome sequencing analysis, a special PoRVA strain, CHN/SD/LYXH2/2022/G4P[6]I1, had high homology with human RV strains, revealing genetic reassortment between human and porcine RV strains in vivo. Our data indicate the high prevalence, major genotypes, and cross-species transmission of porcine RVA in China. Therefore, the continuous monitoring of porcine RVA prevalence is essential, providing valuable insights for virus prevention and control, and supporting the development of candidate vaccines against porcine RVA. [ABSTRACT FROM AUTHOR]

Dysregulation of apoptosis occurs in different types of malignant tumors and is likely to influence the tumor evolution, as well as clinical prognosis. However, the limited number of studies investigating the predictive power of apoptosis-related genes (ARGs) in gastric cancer indicates a gap in the current research. 174 ARGs who differentially expressed were screened using public databases, including the Gene Expression Omnibus and the Molecular Signatures Database. Univariate and LASSO regression analyses were rigorous approaches to recognize the 12 optimal genes (CTHRC1, PDGFRL, VCAN, GJA1, LOX, UPP1, ANGPT2, CRIM1, HIF1A, APOD, RNase1, and ID1) that make up the prognostic risk model. Molecular mutations, related signaling pathways, and immune system characteristics in different subgroups defined by the risk model were analyzed using different R packages. Moreover, based on the database of Genomics of Drug Sensitivity in Cancer, chemotherapy sensitivity was predicted among the risk subgroups. As a result, there were differences in mutation profiles, signaling pathways, and infiltrated immune cells between patients in various risk groups. Moreover, the low-risk group displayed greater sensitivity to chemotherapy than the high-risk group. Risk model provided a better prognostic value than the T, N, and M stages, according to the receiver operating characteristic curve. Finally, in a nomogram, the risk model and clinical factors were combined to visualize the survival rates of patients with GC. In response to the differential expression of apoptosis-related genes, a novel model for predicting the prognosis of GC patients was developed. This model may be highly valuable for guiding doctors to deliver treatment plans tailored to the need of patients with GC.

Background: RBM10 is commonly mutated in lung adenocarcinoma (LUAD). However, its role in the pathogenesis of LUAD remains undefined. EGFR-mutant LUAD represents a distinct subset of non-small cell lung cancer (NSCLC). The function of RBM10 in tumor pathogenesis is supposed to differ between EGFR-mutant and EGFR-wt LUAD. This study aimed to interrogate the prevalence of RBM10 mutation in a large cohort of Chinese patients with LUAD and investigate the association of RBM10 mutation with clinical and molecular characteristics of EGFR-mutant and EGFR-wt LUAD. Methods: Tumor sequencing data from 2848 Chinese patients with LUAD were retrospectively reviewed and analyzed. The prevalence of RBM10 was also compared with other three cohorts: OrigMed (n = 1222), MSKCC (n = 1267), and TCGA (n = 566). The associations of RBM10 mutation with clinical and molecular characteristics were assessed. An external cohort of 182 patients with LUAD who received PD-1 inhibitor were used to investigate the association of RBM10 mutation with clinical outcomes upon immunotherapy. Results: Our cohort showed a higher prevalence of RBM10 in EGFR-mutant LUAD than in EGFR-wt LUAD (14.8 % vs. 6.5 %, p

Abstract Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a very rare lung tumor that accounts for less than 0.09% of all primary lung tumors and has no specific epidemiology. The correct diagnosis requires imaging, laboratory, pathological, immunohistochemical, and molecular examination. The most typical feature of pulmonary HCCC is the clear cell component with clear stroma. In addition, the fusion gene EWSR1::ATF1 due to t(12;22)(q13;q12) is essential for the pathological diagnosis of pulmonary HCCC. The main treatment for pulmonary HCCC is surgery. This review focus on the pathological features, immunohistochemical examination, mutation analysis and treatment of pulmonary HCCC.

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a very rare lung tumor that accounts for less than 0.09% of all primary lung tumors and has no specific epidemiology. The correct diagnosis requires imaging, laboratory, pathological, immunohistochemical, and molecular examination. The most typical feature of pulmonary HCCC is the clear cell component with clear stroma. In addition, the fusion gene EWSR1::ATF1 due to t(12;22)(q13;q12) is essential for the pathological diagnosis of pulmonary HCCC. The main treatment for pulmonary HCCC is surgery. This review focus on the pathological features, immunohistochemical examination, mutation analysis and treatment of pulmonary HCCC. [ABSTRACT FROM AUTHOR]

Introduction: Shewanella is an important opportunistic pathogen distributed in marine environments that has caused an increasing number of clinical infections. However, there are few reports on the distribution and characteristics of Shewanella in the diarrheal pathogen spectrum. In this study, we have systematically described the prevalence of Shewanella infections in diarrhea patients in Beijing, China 2017-2019, and genome characteristics and antimicrobial susceptibility of Shewanella isolates. Methods: Stool samples were collected from diarrhea patients in a surveillance project from 2017 to 2019. Shewanella strains were isolated, and identified using VITEKR 2 COMPACT and MALDI-TOF MS. Average nucleotide identity (ANI) analysis, multi-locus sequence typing (MLST), phylogenetic analysis, virulence-associated genes and antimicrobial resistance genes analysis were used for genome characteristics description. The antibiotic susceptibility test was performed with microbroth dilution method. Results: 1104 fecal samples were collected, and the Shewanella detection rate was 2.36% (26/1104). The main manifestations of infection caused by Shewanella spp. were diarrhea (100%, 26/26), abdominal pain (65.38%, 17/26), and vomiting (38.46%, 10/26). The 26 isolates were classified into 3 species (S. algae (n = 18), S. indica (n = 5), and S. chilikensis (n = 3)) and 22 sequence types. Core genome single nucleotide polymorphism-based evolutionary tree identified three clone groups corresponding to three infection events in the same months in 2017 and 2019. The putative virulence-associated gene pool consisted of 56 potential virulence genes, including 19 virulence gene factors. The resistance rates of the 26 isolates to 17 antibiotics from high to low were as follows: polymyxin E (76.92%), cefotaxime (57.69%), ampicillin (50%), ampicillin-sulbactam (34.62%), nalidixic acid (15.38%), ciprofloxacin (11.54%), selectrin (3.846%,1/26), and tetracycline (3.846%, 1/26). The rate of multidrug resistance was 38.46% (10/26). Discussion: Monitoring for Shewanella spp. should be added to the routine surveillance of infectious diarrhea during the epidemic season. [ABSTRACT FROM AUTHOR]

Objective To explore the antitumor efficacy of tumor-treating fields (TTFields) and identify potential molecular markers for predicting patient response to TTFields therapy. Methods The clinical and genetic data of 100 newly diagnosed glioblastoma (ndGBM) patients who underwent TTFields therapy at Huashan Hospital from August 2018 to June 2023 were analyzed retrospectively. An additional control group of 195 ndGBM patients who did not undergo TTFields therapy was selected. Kaplan-Meier analysis was utilized to assess survival differences between the TTFields therapy group and the control group, with intergroup comparisons performed using the log-rank test. Multivariate Cox regression analysis was employed to investigate factors influencing the efficacy of TTFields therapy. Results In the TTFields therapy group, the median overall survival (OS) was 23.0 months (95% CI=17-NA), whereas the control group exhibited a median OS of 15.1 months (95% CI=13-18). Median progression-free survival (PFS) in the TTFields therapy group was 17 months (95% CI=12-NA), compared to 12 months (95% CI=9~12) in the control group. Multivariate Cox regression analysis results revealed statistically significant effects of PTEN mutation (HR=0.15, 95% CI:0.034-0.63) and EGFR amplification (HR=5.67, 95% CI=1.455-22.05) on PFS in the TTFields therapy group (both P＜0.05). Additionally, TERT mutation significantly influenced OS in the TTFields therapy group ( HR = 3. 96, 95% CI = 1. 308-12. 0, P ＜0. 05). Conclusions TTFields therapy significantly prolongs patient survival. PTEN mutation and EGFR amplification emerge as independent potential molecular markers for predicting PFS in response to TTFields therapy, while TERT mutation serves as a potential marker for predicting OS in TTFields-treated patients. [ABSTRACT FROM AUTHOR]

Fiber demand and production of man-made cellulose fibers (MMCFs) such as Viscose rayon, Modal and Lyocell fibers have been increasing in recent years. Today they are mostly manufactured using wood dissolving pulps. However, the growing fiber demand cannot be satisfied by dissolving pulps from wooden sources only. So, alternative pulps, also based on non-wooden materials, are needed. In this study, novel pulps, namely hemp and oil flax from biogenic residues, untreated and enzymatically treated paper pulps and recycled cotton waste, were investigated and compared to wood dissolving pulps and used for application in Lyocell dissolution and solution spinning procedures using N-methylmorpholin-N-oxide. As a function of degree of polymerization (DP), molecular weight distribution (MWD) and polydispersity (PDI), three groups of pulps with distinct characteristics could be identified. Paper pulp offered the highest DP and PDI values and the broadest MWD. Properties similar to those of wood dissolving pulps could be achieved by an enzymatic treatment. Pulps from biogenic residues exhibited a different behavior. Hemp shives-based pulp held properties comparable to wood dissolving pulps. In contrast, fiber-based oil flax and hemp pulp possessed low PDI values and tight MWDs more comparable to pulp made from recycled cotton fibers. Pulp characteristics were also found to affect the rheological behavior of spinning solutions prepared from these pulps. In summary, suitable dissolving pulps have specific impacts on solution spinning of MMCF. A careful analytical characterization by means of molecular and rheological approaches is mandatory before using a pulp in fiber spinning activities. [ABSTRACT FROM AUTHOR]

Intraductal carcinoma of the prostate (IDC‐P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC‐P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC‐P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

[Objective] The purpose of the study was to clone heat shock protein Hsp70 gene from Apocheima cinerarius, analyze its physicochemical properties and expression, and explore the role of this gene in coping with the adverse environment of A. cinerarius. [Method] In the study, Hsp70 was cloned and named as AcinHsp70 (GenBank entry number: OP750249) based on the transcriptome data (under different low temperature stress of A. cinerarius larvae). The physical and chemical properties of Hsp70 gene were analyzed by using bioinformation analysis software. qPCR was used to detect the expression profiles of AcinHsp70 under different temperature stresses (10,5, 0, 5 and 25 °C) and under different time treatments at 4 °C. [Result] The total length of CDS of AcinHsp70 sequence was 1899 bp, encoding 633 amino acids, the molecular weight of protein was 69.91 kDa, and the isoelectric point was 5.51. The N-terminus of the protein lacked a signal peptide and transmembrane region. Phosphorylation sites were identified at serine, threonine and tyrosine residues (24, 26, and 8 sites respectively). No glycosylation sites were observed. The average hydrophilicity of the protein was 0.507, with a predicted instability coefficient of 33. 19, indicating its stability as a hydrophilic protein. Subcellular localization analysis revealed predominant cytoplasmic distribution. The results of sequence comparison and phylogenetic analysis showed that the A. cinerarius was closely related to Melitaea cinxia, and the sequence identity reached 92.91%. Gene expression results showed that AcinHsp70 expression was not significantly different under different temperature (except for 10 °C) stress, and the expression was significantly up-regulated after recovery. The expression level of the AcinHsp70 exhibited an initial increase followed by a subsequent decrease, with maximum expression after 1 hour treatment at 4 °C. [Conclusion] AcinHsp70 is closely related to the response of A. cinerarius to low temperature stress, and the results help to reveal the molecular function of Acinhsp70 under low temperature stress. [ABSTRACT FROM AUTHOR]

Main conclusion: This review provides a detailed description of the function and mechanism of VQ family gene, which is helpful for further research and application of VQ gene resources to improve crops. Valine-glutamine (VQ) motif-containing proteins are a large class of transcriptional regulatory cofactors. VQ proteins have their own unique molecular characteristics. Amino acids are highly conserved only in the VQ domain, while other positions vary greatly. Most VQ genes do not contain introns and the length of their proteins is less than 300 amino acids. A majority of VQ proteins are predicted to be localized in the nucleus. The promoter of many VQ genes contains stress or growth related elements. Segment duplication and tandem duplication are the main amplification mechanisms of the VQ gene family in angiosperms and gymnosperms, respectively. Purification selection plays a crucial role in the evolution of many VQ genes. By interacting with WRKY, MAPK, and other proteins, VQ proteins participate in the multiple signaling pathways to regulate plant growth and development, as well as defense responses to biotic and abiotic stresses. Although there have been some reports on the VQ gene family in plants, most of them only identify family members, with little functional verification, and there is also a lack of complete, detailed, and up-to-date review of research progress. Here, we comprehensively summarized the research progress of VQ genes that have been published so far, mainly including their molecular characteristics, biological functions, importance of VQ motif, and working mechanisms. Finally, the regulatory network and model of VQ genes were drawn, a precise molecular breeding strategy based on VQ genes was proposed, and the current problems and future prospects were pointed out, providing a powerful reference for further research and utilization of VQ genes in plant improvement. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to verify TCGA subtypes in endometrial clear cell carcinoma (ECCC) and determine their clinical and molecular characteristics. Methods: We summarized and compared the clinical features of 28 clear cell carcinoma and 112 endometrioid carcinoma patients. Of the 28 ECCCs, 19 underwent TCGA classification, and other markers (ER, PR, ARID1A, ARIB1B, TAF1, and HER-2) were also detected by IHC, and outcomes were assessed. Results: Compared to endometrioid carcinoma, ECCC had an older age of onset (median age, 64.5 years, range 31-81 years), higher rate of myometrial invasion (42.8% vs. 21.5% in endometrioid carcinoma), LVSI (33% vs. 16%), and more advanced FIGO stage. Among the ECCCs, LVSI was a poor prognostic factor. TCGA classification was performed for 19 ECCCs: two POLEmut cases (10.5%), three MMRd (15.8%), 11 p53wt (57.9%), and three p53abn (15.8%). Of the 19 ECCCs, six (31.6%) showed HER-2 positive expression, and eight (42.1%) had TAF1 expression loss. ECCCs possessed HER-2 and TAF1 expression had worse outcomes. Conclusion: Our study summarized the clinical features of ECCC. The outcomes of patients with ECCC with TCGA subtypes differed from those of patients with endometrioid carcinoma. HER-2 and TAF1 may be new prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract Background As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. Methods We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co‐mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. Results Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI‐positive and one was MVI‐negative, and there was a co‐occurrence of TERTp and TP53 (p

Introduction: Dissolved organic matter (DOM) as primary and secondary energy sources can be transported via rivers to estuaries and impact coastal biogeochemical cycles. Storm-induced high discharge events can alter the dominant river flow paths and enhance leaching of shallow organic-rich soil layers, leading to elevated terrestrial DOM export. Land use/land cover (LULC) and associated anthropogenic interventions (including artificial reservoirs and agricultural irrigation) can control sources and transformation processes of exported DOM along with hydrologic factors. The relative significance of LULC, hydrological factors, and temperature variations with seasons will differ depending on geographical locations and complicate their incorporation in biogeochemical models of DOM dynamics. This study investigates the role of LULC, seasonality, and storm events on DOM concentrations and molecular composition in the Murderkill River system.Method: Surface water samples were collected seasonally and before/after storm events from 6 sites representing forested, agricultural, and developed LULC units. The DOM was characterized via parallel factor analysis of excitation-emission matrix data and electrospray ionization 21 T Fourier-transform ion cyclotron resonance mass spectrometry to determine potential DOM sources and enable the development of a conceptual model for DOM dynamics in rivers impacted by anthropogenic reservoirs.Result and Discussion: Our results suggest that storm-induced shallow and overland flow paths can increase surface-vegetation/plant-litter derived DOM based on atomic ratios associated with specific biogenic precursors (i.e., lignin, tannins, and/or oxygenated aromatic DOM), particularly in winter when autochthonous production was suppressed due to reduced temperatures. We further demonstrate that the damming effects of artificial reservoirs enhance the role of seasonal patterns of autochthonous production, disrupting storm-shunt process and stimulating significantly more bio-produced DOM export during spring and summer (i.e., tryptophan/tyrosine-like. N- and S- containing, phytoplankton-derived compounds). Collectively, these results demonstrate how artificial reservoirs alter the characteristics of DOM exported from rivers with implications for understanding carbon export and fate at river-estuary interfaces.