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1.
Org Lett ; 26(36): 7744-7750, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39235307

ABSTRACT

A chemoselective and regioselective copper-promoted defunctionalization procedure has been developed, enabling the rapid construction of various N-polyheterocycles. Initial mechanistic studies reveal that a single-electron transfer radical process is potentially involved.

2.
Food Chem ; 463(Pt 1): 140844, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39236387

ABSTRACT

Integrating plant proteins into meat products offers a sustainable way to reduce the environmental impact of meat consumption while satisfying the growing flexitarian population. This study explored the effects of textured vegetable proteins (TVPs) on the physico-chemical attributes and flavour profile of hybrid salamis using 4D label-free proteomics. Results showed that hybrid salamis had lower pH, reduced water activity and increased weight loss compared with traditional salamis, along with greater hardness and a slightly rough, porous texture with a filamentous structure. TVPs substantially modified crucial meaty flavour compounds (nitrogen oxides, sulfides and pyrazine), increasing heightening sourness and bitterness while diminishing umami. Proteomic analysis revealed significant upregulation of myosin and actin in hybrid salamis; notably, these proteins were involved in glycerol-3-phosphate dehydrogenase activity and calcineurin-mediated signalling, underscoring their role in flavour enhancement. Therefore, hybrid salamis offer an attractive alternative to traditional salamis by merging meat-like taste and texture with plant protein.

3.
Cell Discov ; 10(1): 92, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39223112

ABSTRACT

Human ABC transporters ABCD1-3 are all localized on the peroxisomal membrane and participate in the ß-oxidation of fatty acyl-CoAs, but they differ from each other in substrate specificity. The transport of branched-chain fatty acids from cytosol to peroxisome is specifically driven by ABCD3, dysfunction of which causes severe liver diseases such as hepatosplenomegaly. Here we report two cryogenic electron microscopy (cryo-EM) structures of ABCD3 bound to phytanoyl-CoA and ATP at resolutions of 2.9 Å and 3.2 Å, respectively. A pair of phytanoyl-CoA molecules were observed in ABCD3, each binding to one transmembrane domain (TMD), which is distinct from our previously reported structure of ABCD1, where each fatty acyl-CoA molecule strongly crosslinks two TMDs. Upon ATP binding, ABCD3 exhibits a conformation that is open towards the peroxisomal matrix, leaving two extra densities corresponding to two CoA molecules deeply embedded in the translocation cavity. Structural analysis combined with substrate-stimulated ATPase activity assays indicated that the present structures might represent two states of ABCD3 in the transport cycle. These findings advance our understanding of fatty acid oxidation and the molecular pathology of related diseases.

4.
J Agric Food Chem ; 72(38): 20794-20804, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39276343

ABSTRACT

Azobenzene moieties can serve as active fragments in antimicrobials and exert trans/cis conversions of molecules. Herein, a series of novel nicotinamide derivatives (NTMs) were developed by employing a two-step strategy, including azo-incorporating and bioisosteric replacement. Azo-incorporation can conveniently provide compounds that can be easily optically interconverted between trans/cis isomers, enhancing the structural diversity of azo compounds. It is noteworthy that the replacement of the azo bond with a 1,2,4-oxadiazole motif through further bioisosteric replacement led to the discovery of a novel compound, NTM18, which made a breakthrough in preventing rice sheath blight disease. A control effect value of 94.44% against Rhizoctonia solani could be observed on NTM18, while only 11.11% was determined for boscalid at 200 mg·L-1. Further mechanism validations were conducted, and the molecular docking analysis demonstrated that compound NTM18 might have a tight binding with SDH via an extra π-π interaction between the oxadiazole ring and residue of D_Y586. This work sets up a typical case for the united applications of azo-incorporating and bioisosteric replacement in fungicide design, posing an innovative approach in structural diversity-based development of pesticides.


Subject(s)
Azo Compounds , Fungicides, Industrial , Molecular Docking Simulation , Niacinamide , Oryza , Plant Diseases , Rhizoctonia , Niacinamide/chemistry , Azo Compounds/chemistry , Rhizoctonia/drug effects , Rhizoctonia/chemistry , Oryza/chemistry , Oryza/microbiology , Plant Diseases/microbiology , Plant Diseases/prevention & control , Fungicides, Industrial/chemistry , Fungicides, Industrial/pharmacology , Molecular Structure , Structure-Activity Relationship
6.
Chem Biodivers ; : e202401767, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39185921

ABSTRACT

Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold-hopping strategies were employed in the rational design of pyridylhydrazono derivatives as potential insect TRPV channels modulators. Insecticidal bioassay demonstrated that the initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with the optimal compound B3 exhibiting a mortality rate of 53.3% against Aphis craccivora at 400 mg·L-1. Conformation analysis indicated that the high energy barrier required for the transition from the lowest-energy conformation to the active conformation may be a key factor contributing to the reduced insecticidal activities of the target compounds. Further structural optimizations aimed at reducing this energy barrier through binding mode-based conformation regulation led to the identification of optimal target 4-(3'-pyridylhydrazono)pyrazol-5-one derivatives C1 and C2. These compounds exhibited reduced transition energy barriers and improved insecticidal activity, with moderate mortality rate of 66.3% and 75.7% against A. craccivora at 400 mg·L-1, respectively. These findings provide valuable insights for future research on the discovery of insect TRPV modulators and have significant implications for the development of more effective agricultural insecticides.

7.
Comput Methods Programs Biomed ; 255: 108323, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39029417

ABSTRACT

BACKGROUND AND OBJECTIVE: Patient-ventilator asynchrony (PVA) is associated with poor clinical outcomes and remains under-monitored. Automated PVA detection would enable complete monitoring standard observational methods do not allow. While model-based and machine learning PVA approaches exist, they have variable performance and can miss specific PVA events. This study compares a model and rule-based algorithm with a machine learning PVA method by retrospectively validating both methods using an independent patient cohort. METHODS: Hysteresis loop analysis (HLA) which is a rule-based method (RBM) and a tri-input convolutional neural network (TCNN) machine learning model are used to classify 7 different types of PVA, including: 1) flow asynchrony; 2) reverse triggering; 3) premature cycling; 4) double triggering; 5) delayed cycling; 6) ineffective efforts; and 7) auto triggering. Class activation mapping (CAM) heatmaps visualise sections of respiratory waveforms the TCNN model uses for decision making, improving result interpretability. Both PVA classification methods were used to classify incidence in an independent retrospective clinical cohort of 11 mechanically ventilated patients for validation and performance comparison. RESULTS: Self-validation with the training dataset shows overall better HLA performance (accuracy, sensitivity, specificity: 97.5 %, 96.6 %, 98.1 %) compared to the TCNN model (accuracy, sensitivity, specificity: 89.5 %, 98.3 %, 83.9 %). In this study, the TCNN model demonstrates higher sensitivity in detecting PVA, but HLA was better at identifying non-PVA breathing cycles due to its rule-based nature. While the overall AI identified by both classification methods are very similar, the intra-patient distribution of each PVA type varies between HLA and TCNN. CONCLUSION: The collective findings underscore the efficacy of both HLA and TCNN in PVA detection, indicating the potential for real-time continuous monitoring of PVA. While ML methods such as TCNN demonstrate good PVA identification performance, it is essential to ensure optimal model architecture and diversity in training data before widespread uptake as standard care. Moving forward, further validation and adoption of RBM methods, such as HLA, offers an effective approach to PVA detection while providing clear distinction into the underlying patterns of PVA, better aligning with clinical needs for transparency, explicability, adaptability and reliability of these emerging tools for clinical care.


Subject(s)
Algorithms , Machine Learning , Neural Networks, Computer , Respiration, Artificial , Humans , Retrospective Studies , Male , Female , Middle Aged , Aged , Ventilators, Mechanical , Patient-Ventilator Asynchrony
8.
Integr Zool ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39030865

ABSTRACT

The intricate process of shell biomineralization in marine molluscs is governed by a complex interplay of regulatory elements, encompassing secretomes, transporters, and noncoding RNA. This review delves into recent advancements in understanding these regulatory mechanisms, emphasizing their significance in elucidating the functions and evolutionary dynamics of the molluscan shell biomineralization process. Central to this intricate orchestration are secretomes with diverse functional domains, selectively exported to the extrapallial space, which directly regulate crystal growth and morphology. Transporters are crucial for substrate transportation in the calcification and maintenance of cellular homeostasis. Beyond proteins and transporters, noncoding RNA molecules are integral components influencing shell biomineralization. This review underscores the nonnegligible roles played by these genetic elements at the molecular level. To comprehend the complexity of biomineralization in mollusc, we explore the origin and evolutionary history of regulatory elements, primarily secretomes. While some elements have recently evolved, others are ancient genes that have been co-opted into the biomineralization toolkit. These elements undergo structural and functional evolution through rapidly evolving repetitive low-complexity domains and domain gain/loss/rearrangements, ultimately shaping a distinctive set of secretomes characterized by both conserved features and evolutionary innovations. This comprehensive review enhances our understanding of molluscan biomineralization at the molecular and genetic levels.

9.
Int J Food Microbiol ; 422: 110826, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39024730

ABSTRACT

This study investigated the safety characteristics and potential probiotic properties of Enterococcus faecium by using whole genome analysis, and then explored the effect of this strain on the virulence of Listeria monocytogenes in vitro and during the storage of fermented sausages. Results showed that E. faecium B1 presented enterocin A, B, and P, enterolysin A, and UviB, and the exotoxin related genes and exoenzyme related genes were not detected in the genome of E. faecium B1. However, the adherence genes including acm and scm were present in this strain, which also positively correlated with characteristics related to probiotic potential. In addition, E. faecium could adapt to the condition of fermented sausages, and decrease the survival of L. monocytogenes in vitro and in vivo. The expression of the virulence genes (prfA, hly, inlA, and inlB) and sigB-related genes (prli42, rsbT, rsbU, rsbV, rsbW, and sigB) were all inhibited by E. faecium B1 to different extents during the storage of fermented sausages at 4 °C. Moreover, compared with the E. faecium B1 group, the expression level of entA, entB, and entP genes of E. faecium B1 in the co-culture of fermented sausages was increased during the storage, which may be the inhibition mechanism of E. faecium B1 on L. monocytogenes. These results demonstrated that E. faecium B1 could potentially be used as bio-protection to control L. monocytogenes in meat products.


Subject(s)
Enterococcus faecium , Fermentation , Food Microbiology , Listeria monocytogenes , Meat Products , Listeria monocytogenes/genetics , Listeria monocytogenes/pathogenicity , Enterococcus faecium/genetics , Enterococcus faecium/pathogenicity , Meat Products/microbiology , Virulence/genetics , Animals , Genome, Bacterial , Probiotics , Food Storage , Virulence Factors/genetics , Whole Genome Sequencing , Fermented Foods/microbiology , Mice , Swine
10.
J Clin Res Pediatr Endocrinol ; 16(3): 323-333, 2024 09 05.
Article in English | MEDLINE | ID: mdl-38828884

ABSTRACT

Objective: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m2, p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m2, p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m2, p<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Overweight , Pediatric Obesity , Randomized Controlled Trials as Topic , Humans , Adolescent , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Overweight/drug therapy , Pediatric Obesity/drug therapy , Blood Glucose/drug effects , Exenatide/therapeutic use , Exenatide/administration & dosage , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Liraglutide/therapeutic use , Treatment Outcome , Obesity/drug therapy , Glucagon-Like Peptide-1 Receptor Agonists
11.
Pest Manag Sci ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940289

ABSTRACT

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross-resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS: Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole ß-ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D-QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half-maximal effective concentration (EC50) value of 0.0398 µg mL-1 comparable to that for fluxapyroxad (EC50 = 0.0375 µg mL-1), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half-maximal inhibitory concentration of 0.0425 µm. Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen-bonds, and cation-π and π-π interactions. CONCLUSION: The identified ß-ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry.

12.
Chemistry ; 30(44): e202401371, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-38825569

ABSTRACT

Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.

13.
Structure ; 32(8): 1110-1120.e4, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-38823379

ABSTRACT

Carboxysomes are large self-assembled microcompartments that serve as the central machinery of a CO2-concentrating mechanism (CCM). Biogenesis of carboxysome requires the fine organization of thousands of individual proteins; however, the packaging pattern of internal RuBisCOs remains largely unknown. Here we purified the intact ß-carboxysomes from Synechococcus elongatus PCC 7942 and identified the protein components by mass spectrometry. Cryo-electron tomography combined with subtomogram averaging revealed the general organization pattern of internal RuBisCOs, in which the adjacent RuBisCOs are mainly arranged in three distinct manners: head-to-head, head-to-side, and side-by-side. The RuBisCOs in the outermost layer are regularly aligned along the shell, the majority of which directly interact with the shell. Moreover, statistical analysis enabled us to propose an ideal packaging model of RuBisCOs in the ß-carboxysome. These results provide new insights into the biogenesis of ß-carboxysomes and also advance our understanding of the efficient carbon fixation functionality of carboxysomes.


Subject(s)
Bacterial Proteins , Cryoelectron Microscopy , Electron Microscope Tomography , Ribulose-Bisphosphate Carboxylase , Synechococcus , Synechococcus/metabolism , Electron Microscope Tomography/methods , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Ribulose-Bisphosphate Carboxylase/metabolism , Ribulose-Bisphosphate Carboxylase/chemistry , Cryoelectron Microscopy/methods , Models, Molecular
14.
Nano Lett ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848333

ABSTRACT

The intricate interplay between light and matter provides effective tools for manipulating topological phenomena. Here, we theoretically propose and computationally show that circularly polarized light holds the potential to transform the axion insulating phase into a quantum anomalous Hall state in MnBi2Te4 thin films, featuring tunable Chern numbers (ranging up to ±2). In particular, we reveal the spatial rearrangement of the hidden layer-resolved anomalous Hall effect under light-driven Floquet engineering. Notably, upon Bi2Te3 layer intercalation, the anomalous Hall conductance predominantly localizes in the nonmagnetic Bi2Te3 layers that hold zero Berry curvature in the intact state, suggesting a significant magnetic proximity effect. Additionally, we estimate variations in the magneto-optical Kerr effect, giving a contactless method for detecting topological transitions. Our work not only presents a strategy to investigate emergent topological phases but also sheds light on the possible applications of the layer Hall effect in topological antiferromagnetic spintronics.

15.
BMC Pediatr ; 24(1): 330, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741052

ABSTRACT

BACKGROUND: Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis between the alpha and beta globin chains. Thalassemia gene detection technology is the gold standard to achieve accurate detection of thalassemia, but in clinical practice, most of the tests are only for common genotypes, which can easily lead to missing or misdiagnosis of rare thalassemia genotypes. CASE PRESENTATION: We present the case of an 18-year-old Chinese female with abnormal values of routine hematological indices who was admitted for genetic screening for thalassemia. Genomic DNA was extracted and used for the genetic assays. Gap polymerase chain reaction and agarose gel electrophoresis were performed to detect HBA gene deletions, while PCR-reverse dot blot hybridization was used to detect point mutations in the HBA and HBB genes. Next-generation sequencing and third-generation sequencing (TGS) were used to identify known and potentially novel genotypes of thalassemia. We identified a novel complex variant αHb WestmeadαHb Westmeadαanti3.7/-α3.7 in a patient with rare alpha-thalassemia. CONCLUSIONS: Our study identified a novel complex variant that expands the thalassemia gene variants spectrum. Meanwhile, the study suggests that TGS could effectively improve the specificity of thalassemia gene detection, and has promising potential for the discovery of novel thalassemia genotypes, which could also improve the accuracy of genetic counseling. Couples who are thalassemia carriers have the opportunity to reduce their risk of having a child with thalassemia.


Subject(s)
alpha-Thalassemia , Humans , alpha-Thalassemia/genetics , alpha-Thalassemia/diagnosis , Female , Adolescent , High-Throughput Nucleotide Sequencing , Genotype , Genetic Testing/methods , Point Mutation , Hemoglobins, Abnormal/genetics
16.
Microbiol Spectr ; 12(6): e0029824, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38695606

ABSTRACT

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.


Subject(s)
Bacteriophages , Microcystis , Microcystis/virology , Microcystis/genetics , Microcystis/metabolism , Bacteriophages/genetics , Bacteriophages/physiology , China , Transcriptome , Lakes/microbiology , Lakes/virology , Genome, Viral/genetics , Evolution, Molecular
17.
Int J Gynecol Cancer ; 34(7): 1034-1040, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38724236

ABSTRACT

OBJECTIVE: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction. METHODS: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3-5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival. RESULTS: Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3-5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85-100%; n=29) and for cediranib 88% (IQR 76-93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4-11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1-20.4 months; n=17). Median follow-up was 12.4 months (8.9-not reached; n=17). CONCLUSIONS: The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated. TRIAL REGISTRATION NUMBER: EudraCT 2016-004618-93.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Intestinal Obstruction , Ovarian Neoplasms , Paclitaxel , Quinazolines , Humans , Female , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/complications , Aged , Intestinal Obstruction/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Quinazolines/administration & dosage , Quinazolines/adverse effects , Drug Resistance, Neoplasm , Adult , Drug Administration Schedule , Carcinoma, Ovarian Epithelial/drug therapy , Indoles
18.
Food Res Int ; 186: 114312, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729688

ABSTRACT

Listeria monocytogenes exhibits varying levels of pathogenicity when entering the host through contaminated food. However, little is known regarding the stress response and environmental tolerance mechanism of different virulence strains to host gastrointestinal (GI) stimuli. This study analyzed the differences in the survival and genes of stress responses among two strains of L. monocytogenes 10403S (serotype 1/2a, highly virulent strain) and M7 (serotype 4a, low-virulence strain) during simulated gastrointestinal digestion. The results indicated that L. monocytogenes 10403S showed greater acid and bile salt tolerance than L. monocytogenes M7, with higher survival rates and less cell deformation and cell membrane permeability during the in vitro digestion. KEGG analysis of the transcriptomes indicated that L. monocytogenes 10403S displayed significant activity in amino acid metabolism, such as glutamate and arginine, associated with acid tolerance. Additionally, L. monocytogenes 10403S demonstrated a higher efficacy in promoting activities that preserve bacterial cell membrane integrity and facilitate flagellar protein synthesis. These findings will contribute valuable practical insights into the tolerance distinctions among different virulence strains of L. monocytogenes in the GI environment.


Subject(s)
Food Microbiology , Gastrointestinal Tract , Listeria monocytogenes , Meat Products , Listeria monocytogenes/pathogenicity , Listeria monocytogenes/genetics , Listeria monocytogenes/metabolism , Meat Products/microbiology , Virulence , Gastrointestinal Tract/microbiology , Bile Acids and Salts/metabolism , Digestion , Food Contamination , Microbial Viability , Cell Membrane Permeability
19.
World J Gastrointest Surg ; 16(5): 1420-1429, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38817302

ABSTRACT

BACKGROUND: Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gastrointestinal tumor surgery. AIM: To investigate the potential risk factors for gastrointestinal dysfunction following gastrointestinal tumor surgery and to present information supporting the prevention and management of gastrointestinal dysfunction in surgery patients. METHODS: Systematically searched the relevant literature from PubMed, Web of Science, Cochrane Library, Embase, CNKI, China Biomedical Database, Wanfang Database, and Weipu Chinese Journal Database self-established until October 1, 2022. Review Manager 5.3 software was used for meta-analysis after two researchers independently screened literature, extracted data, and evaluated the risk of bias in the included studies. RESULTS: A total of 23 pieces of literature were included, the quality of which was medium or above, and the total sample size was 43878. The results of meta-analysis showed that the patients were male (OR = 1.58, 95%CI: 1.25-2.01, P = 0.002) and ≥ 60 years old (OR = 2.60, 95%CI: 1.76-2.87, P < 0.001), physical index ≥ 25.3 kg/m2 (OR = 1.6, 95%CI: 1.00-1. 12, P = 0.040), smoking history (OR = 1.89, 95%CI: 1.31-2.73, P < 0.001), chronic obstructive pulmonary disease (OR = 1.49, 95%CI: 1.22-1.83, P < 0.001), enterostomy (OR = 1.47, 95%CI: 1.26-1.70, P < 0.001), history of abdominal surgery (OR = 2.90, 95%CI: 1.67-5.03, P < 0.001), surgical site (OR = 1.2, 95%CI: 1.40-2.62, P < 0.001), operation method (OR = 1.68, 95%CI: 1.08-2.62, P = 0.020), operation duration (OR = 2.65, 95%CI: 1.92-3.67, P < 0.001), abdominal adhesion grade (OR = 2.52, 95%CI: 1.90-3.56, P < 0.001), postoperative opioid history (OR = 5.35, 95%CI: 3.29-8.71, P < 0.001), tumor TNM staging (OR = 2.58, 95%CI: 1.84-3.62, P < 0.001), postoperative blood transfusion (OR = 2.92, 95%CI: 0.88-9.73, P = 0.010) is a risk factor for postoperative gastrointestinal dysfunction in patients with gastrointestinal tumors. CONCLUSION: There are many factors affecting gastrointestinal dysfunction in gastrointestinal patients after surgery. Clinical staff should identify relevant risk factors early and implement targeted intervention measures on the basis of personalized assessment to improve the clinical prognosis of patients.

20.
Alpha Psychiatry ; 25(1): 82-87, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38799484

ABSTRACT

Objective: The aim of the study was to identify the risk factors associated with nonsuicidal self-injurious (NSSI) behavior in patients with depressive disorders and develop predictive models utilizing these influencing factors as predictors, followed by validation of the constructed models for their efficacy. Methods: Patients with depression disorders admitted to Wuhan Mental Health Center from 2020 to 2021 were included using retrospective analysis. Patients who exhibited one or more items on the NSSI behavior rating questionnaire were categorized into the NSSI group, while those without any such behaviors were assigned to the non-NSSI group. Patients in both groups were categorized separately based on gender, age, personality traits, and interpersonal relationships. The above data were analyzed using multiple logistic regression analysis. Prediction models were constructed, receiver operating characteristic (ROC) curves were produced and model accuracy was calculated. Results: A total of 237 patients were included in this study, with 122 patients assigned to the NSSI group and 115 patients assigned to the non-NSSI group. By comparing the baseline data of the patients in the 2 groups, the results revealed statistically significant differences between the 2 groups in terms of age, grades at school, early childhood parenting style, Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Experiences in Close Relationships Scale (ECRS) (P<.05). However, no statistically significant differences were observed for the remaining indicators (P>.05). The results of the multiple logistic regression model showed that grades at school, early childhood parenting style, HAMD, HAMA, and ECRS scores were risk factors. The ROC model was constructed using school performance, childhood parenting style, HAMD, HAMA, and ECRS scores as predictors. The findings indicated that the ECRS score was the best predictor of NSSI, and it had a sensitivity of 91.8% and specificity of 70.5% for an area of 0.967. Conclusion: ECRS was utilized as a predictor to evaluate the NSSI inclination of depressed patients with commendable sensitivity and specificity. Furthermore, early childhood parenting style, HAMD, HAMA, and ECRS scores were identified as risk factors for NSSI. For individuals at high risk who exhibit these aforementioned risk factors, clinical diagnosis and treatment should be approached with caution.

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