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1.
World J Emerg Med ; 15(5): 365-371, 2024.
Article in English | MEDLINE | ID: mdl-39290599

ABSTRACT

BACKGROUND: Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism. The present study aimed to establish a new scoring system to predict mechanical ventilation (MV) for botulism patients. METHODS: A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022. Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system. The area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: A total of 153 patients with botulism (66 males and 87 females, with an average age of 43 years) were included. Of these, 49 patients (32.0%) required MV, including 21 (13.7%) with invasive ventilation and 28 (18.3%) with non-invasive ventilation. Multivariate analysis revealed that botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement were independent risk factors for MV. These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system. Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization ([botulinum toxin type A: 1], [pneumonia: 2], [incubation period ≤1 day: 2], [hypoxia <90%: 2], [severity of muscle involvement: grade II, 3; grade III, 7; grade IV, 11]). The scoring system achieved an area under the ROC curve of 0.82 (95% CI 0.75-0.89, P<0.001). At the optimal threshold of 9, the scoring system achieved a sensitivity of 83.7% and a specificity of 70.2%. CONCLUSION: Our study identified botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement as independent risk factors for MV in botulism patients. A score ≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients. This scoring system needs to be validated externally before it can be applied in clinical settings.

2.
BMC Musculoskelet Disord ; 25(1): 735, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39277709

ABSTRACT

PURPOSE: This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. METHODS: This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. RESULTS: The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p < 0.05). Harris and VAS scores were higher in the FNS group than in the CCS group (p < 0.05). Postoperative changes in the neck shaft angle and femoral neck shortening were significantly lower in the FNS group than in the CCS group (p < 0.05). The results of the finite element analysis indicated that the maximum stress on the femoral head and varus angle were generally lower in the FNS group than in the CCS group and that the maximum displacement of the femoral head and FNS was generally lower in the FNS group than in the CCS group. However, the superiority of FNS over CCS decreased with increasing Pauwels angle. Additionally, the effectiveness of FNS in limiting displacement of the femoral neck upper wall was not as favourable as that of CCS. CONCLUSIONS: The treatment of femoral neck fractures with FNS is superior and contributes to improved hip joint function. Biomechanical research has confirmed its structural stability and advantages in resisting femoral head varus. However, challenges to its fixation efficacy persist, particularly at higher Pauwels angles.


Subject(s)
Bone Screws , Femoral Neck Fractures , Fracture Fixation, Internal , Humans , Femoral Neck Fractures/surgery , Femoral Neck Fractures/physiopathology , Female , Male , Retrospective Studies , Middle Aged , Aged , Biomechanical Phenomena , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Treatment Outcome , Fracture Healing , Femur Neck/surgery , Femur Neck/diagnostic imaging , Length of Stay , Aged, 80 and over
3.
Sci Rep ; 14(1): 21475, 2024 09 14.
Article in English | MEDLINE | ID: mdl-39277664

ABSTRACT

This study aims to develop and validate a nomogram for predicting overall survival (OS) in Asian patients with Esophageal Cancer (EC). Data from Asian EC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for initial variable selection, followed by multivariate Cox regression analysis to identify independent prognostic factors. A nomogram was subsequently constructed based on these factors. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves and calibration curves, while the clinical utility of the nomogram was assessed through decision curve analysis (DCA). The LASSO regression and multivariate Cox regression analysis identified age, sex, marital status, tumor size, M stage, surgery, and chemotherapy as independent prognostic factors. The ROC curve results demonstrated that the area under the curve (AUC) values for predicting 1-year, 3-year, and 5-year OS in the training cohort were 0.770, 0.756, and 0.783, respectively. In the validation cohort, the AUC values were 0.814, 0.763, and 0.771, respectively. Calibration curves indicated a high concordance between predicted and actual OS. The DCA demonstrated that the nomogram has significant clinical applicability. This nomogram provides reliable predictions and valuable guidance for personalized survival estimates and high-risk patient identification.


Subject(s)
Esophageal Neoplasms , Nomograms , ROC Curve , SEER Program , Humans , Esophageal Neoplasms/mortality , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Male , Female , Middle Aged , Prognosis , Aged , Asian People , Adult , Proportional Hazards Models
4.
Nat Commun ; 15(1): 7130, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164248

ABSTRACT

Actinide metallacyclic chemistry  has been of interest due to its involvement  in various chemical processes. However, fundamental understanding on the key species, actinide metallacyclic complexes, is limited to metallacyclopropenes whereas little is known about the actinide metallacyclopropynes presumably due to their unusual high reactivity. Herein, we report the preparation of a thorium metallacyclopropyne complex (η2-C ≡ C)ThCl3- in the gas phase by using electrospray ionization mass spectrometry, and it is generated via a single-ligand strategy through sequential losses of CO2 and HCl from the monopropynoate precursor (HC ≡ CCO2)ThCl4- upon collision-induced dissociation. Alternatively, the dual-ligand strategy involving consecutive losses of two CO2 and one C2H2 from the dipropynoate precursor (HC ≡ CCO2)2ThCl3- works as well. According to the reactivity experiments and theoretical calculations, (η2-C ≡ C)ThCl3- possesses a dianionic ligand C22- coordinated to the Th(IV) center in a side-on fashion. Further bonding analysis demonstrates the presence of a triple bond between the two C atoms, and the Th 5 f orbitals are significantly involved in the Th-(C ≡ C) bonding. A Th metallacyclopropyne structure is thus established for (η2-C ≡ C)ThCl3-.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1078-1084, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39192401

ABSTRACT

OBJECTIVE: To investigate the anti- chronic myelogenous leukemia (CML) activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression, and explore the potential role of its signaling pathway. METHODS: Firstly, CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B, imatinib, and their combination on the proliferation and migration of K562 cells. Furthermore, the apoptosis rate of K562 cells treated with Csn-B, imatinib, and their combination was detected by flow cytometry. The expression levels of Nur77, Pim-1, Drp1, p-Drp1 S616, Bcl-2 and Bax in K562 cells were detected by Western blot. Finally, the expression levels of reactive oxygen species (ROS) in K562 cells treated with Csn-B, imatinib and their combination were detected by immunofluorescence assay. RESULTS: The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754 (P < 0.001). Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells (both P < 0.001), and induce apoptosis (P < 0.001). Csn-B promoted Nur77 expression in K562 cells, and synergistically enhanced imatinib sensitivity when combined with imatinib. Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment (both P < 0.001). CONCLUSION: Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.


Subject(s)
Apoptosis , Cell Proliferation , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Nuclear Receptor Subfamily 4, Group A, Member 1 , Proto-Oncogene Proteins c-pim-1 , Humans , Imatinib Mesylate/pharmacology , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Apoptosis/drug effects , K562 Cells , Cell Proliferation/drug effects , Proto-Oncogene Proteins c-pim-1/metabolism , Dynamins , Signal Transduction , Reactive Oxygen Species/metabolism , Cell Movement
6.
Sci Adv ; 10(33): eadn6272, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150998

ABSTRACT

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.


Subject(s)
Anxiety , GABAergic Neurons , Hypothalamic Area, Lateral , Pruritus , Animals , Mice , GABAergic Neurons/metabolism , Chronic Disease , Disease Models, Animal , Midline Thalamic Nuclei/metabolism , Male , Behavior, Animal , Neural Pathways , Neuronal Plasticity , Septal Nuclei
7.
Asian J Androl ; 26(5): 535-543, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39107962

ABSTRACT

ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.


Subject(s)
Cell Proliferation , Extracorporeal Shockwave Therapy , Male , Animals , Rats , Extracorporeal Shockwave Therapy/methods , Humans , Prostate/pathology , Prostatitis/therapy , DNA Damage , Rats, Sprague-Dawley , Cell Movement , Prostatic Neoplasms/therapy
8.
Viruses ; 16(8)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39205312

ABSTRACT

Salmonella Typhimurium (S. Typhimurium) contamination poses a significant challenge to breeder egg hatchability and chick health, necessitating the exploration of alternative disinfection methods. This study investigates the potential of phage vB_SPuM_SP02 (SP02) as a novel disinfectant for breeder eggs contaminated with S. Typhimurium SM022. Phage SP02 was isolated from poultry farm effluent and characterized for morphology, biological properties, and genome properties. Experimental groups of specific pathogen-free (SPF) eggs were treated with Salmonella and phage SP02, and efficacy was assessed through hatching rates, chick survival, weight, Salmonella load, immune organ indices, and intestinal flora. Phage treatment effectively eradicated Salmonella contamination on eggshells within 12 h, resulting in increased hatching and survival rates compared to controls. Furthermore, phage treatment mitigated weight loss and tissue Salmonella load in chicks without causing immune organ damage while reducing Salmonella spp. abundance in the intestinal tract. This study demonstrates the potential of phage SP02 as an eco-friendly and efficient disinfectant for S. Typhimurium-contaminated breeder eggs, offering promising prospects for practical application in poultry production.


Subject(s)
Chickens , Eggs , Salmonella Infections, Animal , Salmonella Phages , Salmonella typhimurium , Animals , Salmonella typhimurium/virology , Salmonella Phages/physiology , Salmonella Phages/isolation & purification , Salmonella Infections, Animal/microbiology , Eggs/microbiology , Eggs/virology , Poultry Diseases/microbiology , Poultry Diseases/prevention & control , Poultry Diseases/virology , Disinfectants/pharmacology , Disinfection/methods , Specific Pathogen-Free Organisms , Bacteriophages/physiology , Bacteriophages/isolation & purification , Egg Shell/microbiology
9.
Retina ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39059020

ABSTRACT

BACKGROUND: The traditional suturing method for cyclodialysis cleft usually requires an incision in the sclera for direct suturing, resulting in greater damage and a high risk of postoperative complications. The purpose of this work is to propose a newly intrascleral double continuous suture repair technique for the treatment of cyclodialysis clefts. METHODS: Seven patients with cyclodialysis cleft underwent microinvasive intrascleral double continuous suture repair surgery to restore the attachment of the detached ciliary body to the sclera without scleral incision. All operations were performed by the same surgeon. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), slit lamp and corneal examination results, ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) results were recorded. RESULTS: Closure of the cyclodialysis cleft was achieved in 7 eyes and no obvious complications occurred after the operation. Intraocular pressure increased from preoperatively 6.8 ± 1.35 mmHg (range: 4.8-8.0 mmHg) to postoperatively 12.5 ± 4.0 mmHg (range: 8.0-20.0 mmHg) (paired sample T test, P < 0.01). Best-corrected Snellen visual acuity improved from preoperatively range 20/2000-20/63 to range 20/200-20/25 at final follow-up. CONCLUSION: In short, intrascleral double continuous suture repair surgical is safe and effective in treating cyclodialysis cleft, with minimal surgical trauma.

11.
Front Genet ; 15: 1416283, 2024.
Article in English | MEDLINE | ID: mdl-39040995

ABSTRACT

Introduction: Laying performance is a key factor affecting production efficiency in poultry, but its molecular mechanism is still indistinct. In this study, Yaoshan chickens, a local breed in Guizhou, China, and merchant chickens (GYR) with higher egg yield after the three-line cross improvement hybridization of Yaoshan chickens were used as animal samples. Methods: To explore the regulatory mechanism of the diversities in laying performance, RNA-seq and ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) were used to describe the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens. Results: At the transcriptional level, 288 differentially expressed genes were upregulated in Yaoshan chickens and 353 differentially expressed genes were upregulated in GYR chickens. In addition, GSEA showed that ECM-receptor interactions and the TGF-ß signaling pathway were restrained, resulting in increased egg production in GYR chickens. Furthermore, the upregulation of thiamine and carnitine was identified by metabolomic analysis to facilitate the laying performance of hens. Finally, comprehensive analyses of the transcriptome and metabolome found that thiamine and carnitine were negatively correlated with ECM-receptor interactions and the TGF-ß signaling pathway, which jointly regulate the laying performance of Yaoshan chickens and GYR chickens. Discussion: Taken together, our research delineates differences in the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens during the peak egg production period and provides new hypotheses and clues for further research on poultry egg production performance and the improvement of economic benefits.

12.
Plant Cell ; 36(9): 3824-3837, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39041486

ABSTRACT

Germline fate determination is a critical event in sexual reproduction. Unlike animals, plants specify the germline by reprogramming somatic cells at the late stages of their development. However, the genetic basis of germline fate determination and how it evolved during the land plant evolution are still poorly understood. Here, we report that the plant homeodomain finger protein GERMLINE IDENTITY DETERMINANT (GLID) is a key regulator of the germline specification in liverwort, Marchantia polymorpha. Loss of the MpGLID function causes failure of germline initiation, leading to the absence of sperm and egg cells. Remarkably, the overexpression of MpGLID in M. polymorpha induces the ectopic formation of cells with male germline cell features exclusively in male thalli. We further show that MpBONOBO (BNB), with an evolutionarily conserved function, can induce the formation of male germ cell-like cells through the activation of MpGLID by directly binding to its promoter. The Arabidopsis (Arabidopsis thaliana) MpGLID ortholog, MALE STERILITY1 (AtMS1), fails to replace the germline specification function of MpGLID in M. polymorpha, demonstrating that a derived function of MpGLID orthologs has been restricted to tapetum development in flowering plants. Collectively, our findings suggest the presence of the BNB-GLID module in complex ancestral land plants that has been retained in bryophytes, but rewired in flowering plants for male germline fate determination.


Subject(s)
Gene Expression Regulation, Plant , Marchantia , Plant Proteins , Marchantia/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Germ Cells, Plant/metabolism , Arabidopsis/genetics , Plants, Genetically Modified
13.
Ecotoxicol Environ Saf ; 280: 116540, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38833982

ABSTRACT

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.


Subject(s)
Biodegradation, Environmental , Burkholderiales , Escherichia coli , Polyethylene Terephthalates , Polyethylene Terephthalates/chemistry , Polyethylene Terephthalates/metabolism , Burkholderiales/enzymology , Escherichia coli/genetics , Bacillus anthracis/enzymology , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Protein Engineering
14.
Am J Transl Res ; 16(5): 1757-1768, 2024.
Article in English | MEDLINE | ID: mdl-38883364

ABSTRACT

OBJECTIVE: This study aimed to assess the efficacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in detecting intrathoracic lymph nodes in patients with nasopharyngeal carcinoma (NPC). METHODS: Retrospective data analysis was conducted on individuals who underwent EBUS-TBNA between June 2015 and June 2022. Patients with NPC and enlarged intrathoracic lymph nodes were included. Specimens were categorized as malignant or non-malignant, with final non-malignancy confirmation procedures, or 12 months of clinical follow-up. RESULTS: Among 97 patients, 59 (60.8%) had NPC with intrathoracic lymph node metastasis, 3 (3.1%) had primary lung cancer involving nodes, and 25 (25.8%) showed benign characteristics. Ten cases (10.3%) were false-negative on initial EBUS-TBNA but confirmed as metastatic on follow-up. For NPC patients with intrathoracic lymphadenopathy, EBUS-TBNA exhibited 86.1% sensitivity (62/72), 71.4% negative predictive value (25/35), and 89.7% accuracy (87/97). Multivariate analysis identified increased lymph node short axis (OR: 1.200, 95% CI: 1.024-1.407; P = 0.041), metachronous NPC (OR: 11.274, 95% CI: 2.289-55.528; P = 0.003), and synchronous lung lesions (OR: 19.449, 95% CI: 1.875-201.753; P = 0.001) as independent predictors of malignant intrathoracic lymphadenopathy. Longer lymph node short axis (OR: 1.305, 95% CI: 1.044-1.631; P = 0.019) was independently associated with EBUS-TBNA accuracy. CONCLUSION: EBUS-TBNA effectively diagnoses intrathoracic lymphadenopathy in NPC patients.

15.
Article in English | MEDLINE | ID: mdl-38935471

ABSTRACT

Sparsification and low-rank decomposition are two important techniques to compress deep neural network (DNN) models. To date, these two popular yet distinct approaches are typically used in separate ways; while their efficient integration for better compression performance is little explored, especially for structured sparsification and decomposition. In this article, we perform systematic co-exploration on structured sparsification and decomposition toward compact DNN models. We first investigate and analyze several important design factors for joint structured sparsification and decomposition, including operational sequence, decomposition format, and optimization procedure. Based on the observations from our analysis, we then propose CEPD, a unified DNN compression framework that can co-explore the benefits of structured sparsification and tensor decomposition in an efficient way. Empirical experiments demonstrate the promising performance of our proposed solution. Notably, on the CIFAR-10 dataset, CEPD brings 0.72%-0.45% accuracy increase over the baseline ResNet-56 and MobileNetV2 models, respectively, and meanwhile, the computational costs are reduced by 43.0%-44.2%, respectively. On the ImageNet dataset, our approach can enable 0.10%-1.39% accuracy increase over the baseline ResNet-18 and ResNet-50 models with 59.4%-54.6% fewer parameters, respectively.

16.
Lancet Microbe ; 5(8): 100852, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38734029

ABSTRACT

BACKGROUND: During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season. METHODS: Samples included were collected from patients with influenza who were prospectively recruited during the 2016-17 and 2017-18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed. FINDINGS: Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00-4·00] vs 1·50 [1·00-2·00]; p=0·018). INTERPRETATION: Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies. FUNDING: The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.


Subject(s)
Influenza A Virus, H3N2 Subtype , Influenza, Human , Phylogeny , Reassortant Viruses , Humans , Influenza A Virus, H3N2 Subtype/genetics , Influenza, Human/epidemiology , Influenza, Human/virology , Reassortant Viruses/genetics , Male , Incidence , Female , Retrospective Studies , Adult , Middle Aged , Aged , Seasons , Adolescent , Child , United States/epidemiology , Genome, Viral/genetics , Young Adult , Severity of Illness Index , Child, Preschool , Whole Genome Sequencing
17.
Article in English | MEDLINE | ID: mdl-38757333

ABSTRACT

BACKGROUND: in the current study, a comparative phytochemical analysis was carried out to explore the phenolic and flavonoid contents in the aerial parts of Vicia sativa L and Vicia monantha Retz growing in cultivated, reclaimed, and desert habitats. METHODS: High-performance liquid chromatography (HPLC) was used to detect Vicia methanolic extracts' individual phenolic and flavonoid constituents. The first-time synthesis of cadmium oxide nanoparticles (CdO NPs) using the aqueous extract of V. monantha has been developed using a green approach. Also, the cytotoxicity of V. monantha extract and CdO NPs was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for unveiling them as anti-HAV and anti-AdV. RESULTS: Our results indicated that in the case of desert habitat, the contents of total phenolics (76.37 mg/g) and total flavonoids (65.23 mg/g) of V. monantha were higher than those of V. sativa (67.35 mg/g and 47.34 mg/g, respectively) and the contents of these secondary metabolites were even increased in V. monantha collected from reclaimed land (phenolics: 119.77 mg/g, flavonoids: 88.61 mg/g). Also, V. monantha surpassed V. sativa in the contents of some individual HPLC constituents, and hence, V. monantha was used to synthesize the green CdO NPs and subsequent antiviral tests. The average size of CdO NPs was determined to be 24.28 nm, and the transmission electron microscopy (TEM) images of CdO NPs clearly showed their spherical form and varying particle sizes, with different diameters in the range of 19-29 nm. MTT assay was positive to the exposure of CdO NPs in the normal cell line, proposing that CdO NPs can reduce cell viability. V. monantha extract showed promising antiviral activity against Hepatitis A virus (HAV) and Adenovirus (AdV) with SI of 16.40 and 10.54. On the other hand, CdONPs had poor antiviral activity against HAV with an SI of 4.74 and moderate antiviral activity against AdV with an SI of 10.54. CONCLUSION: V. monantha is now considered a new, valuable natural resource for phenolics and flavonoids, especially when grown in reclaimed soil. The green CdO NPs based on V. monantha extract showed a promising antiviral effect against HAV and AdV.

18.
Front Biosci (Landmark Ed) ; 29(5): 175, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38812310

ABSTRACT

Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuroparesthesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.


Subject(s)
Dry Eye Syndromes , TRPV Cation Channels , TRPV Cation Channels/metabolism , Humans , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/physiopathology , Animals
19.
Microbiome ; 12(1): 84, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725076

ABSTRACT

BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.


Subject(s)
Bacteria , Neural Networks, Computer , Bacteria/genetics , Bacteria/drug effects , Bacteria/classification , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , High-Throughput Nucleotide Sequencing/methods , Computational Biology/methods , Genes, Bacterial/genetics , Drug Resistance, Microbial/genetics , Humans , Deep Learning
20.
Cancer Lett ; 591: 216872, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38642609

ABSTRACT

The tumor-associated macrophages (TAMs) play multifaceted roles in the progression of hepatocellular carcinoma (HCC). However, the involvement of circular RNAs in the interplay between TAMs and HCC remains unclear. Based on Transwell co-culturing and circular RNA sequencing, this study revealed that TAMs enhanced tumor glycolysis and progression by upregulating circMRCKα in HCC cells. Patients with HCC who exhibited elevated circMRCKα levels presented significantly reduced overall survival and greater cumulative recurrence. Notably, we identified a novel functional peptide of 227 amino acids named circMRCKα-227aa, encoded by circMRCKα. Mechanistically, circMRCKα-227aa bound to USP22 and enhanced its protein level to obstruct HIF-1α degradation via the ubiquitin-proteasome pathway, thereby augmenting HCC glycolysis and progression. In clinical HCC samples, a positive correlation was observed between the expression of circMRCKα and the number of infiltrating CD68+ TAMs and expression of USP22. Furthermore, circMRCKα emerged as an independent prognostic risk factor both individually and in conjunction with CD68+ TAMs and USP22. This study illustrated that circMRCKα-227aa, a novel TAM-induced peptide, promotes tumor glycolysis and progression via USP22 binding and HIF-1α upregulation, suggesting that circMRCKα and TAMs could be combined as therapeutic targets in HCC.


Subject(s)
Carcinoma, Hepatocellular , Glycolysis , Liver Neoplasms , RNA, Circular , Tumor-Associated Macrophages , Animals , Female , Humans , Male , Mice , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Peptides/metabolism , Prognosis , RNA, Circular/genetics , RNA, Circular/metabolism , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Myotonin-Protein Kinase/genetics
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