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1.
Heliyon ; 10(11): e32488, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961893

ABSTRACT

Background: Anterior shoulder dislocation is the most common type of shoulder dislocation and is easy to develop into recurrent type, causing economic burden to society. This study uses the bibliometric method to analyze the global research status, hotspots and trends of anterior shoulder dislocation, aiming to promote the exploration of anterior shoulder dislocation. Methods: The literature on anterior shoulder dislocation in the past two decades were retrieved and downloaded from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and bibliometrix package of R software were used to conduct scientific bibliometric analysis of the literature. Finally, some statistical graphics were performed in Graphpad Prism. Results: A total of 3914 publications related to anterior shoulder dislocation from 2003 to 2022 were retrieved and screened from the WOSCC database. The ranking of the analysis results showed that Provencher MT was the author with the highest frequency of occurrence. Rush University was the most notable contributor. The American Journal of Sports Medicine was the most comprehensive journal. The United States was the most prominent country. Keywords related to surgical treatment were more significant than others. Conclusion: In the past two decades, the research output on anterior shoulder dislocation have been increasing year by year. The focus has gradually shifted to surgical treatment. Surgical treatment may continue to be the research hotspots in this field in the future.

2.
bioRxiv ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38948781

ABSTRACT

Parkinson's Disease (PD) is the second most common neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein containing both a kinase and a GTPase, are a leading cause of the familial form of PD. Pathogenic LRRK2 mutations increase LRRK2 kinase activity. While the bulk of LRRK2 is found in the cytosol, the protein associates with membranes where its Rab GTPase substrates are found, and under certain conditions, with microtubules. Integrative structural studies using single-particle cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) have revealed the architecture of microtubule-associated LRRK2 filaments, and that formation of these filaments requires LRRK2's kinase to be in the active-like conformation. However, whether LRRK2 can interact with and form filaments on microtubules in its autoinhibited state, where the kinase domain is in the inactive conformation and the N-terminal LRR domain covers the kinase active site, was not known. Using cryo-ET, we show that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules. While these filaments are stabilized by the same interfaces seen in the active-LRRK2 filaments, we observed a new interface involving the N-terminal repeats that were disordered in the active-LRRK2 filaments. The helical parameters of the autoinhibited-LRRK2 filaments are different from those reported for the active-LRRK2 filaments. Finally, the autoinhibited-LRRK2 filaments are shorter and less regular, suggesting they are less stable.

3.
Crit Rev Anal Chem ; : 1-20, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978228

ABSTRACT

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

4.
Poult Sci ; 103(9): 103926, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38964253

ABSTRACT

The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its "therapy" effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.

5.
J Biophotonics ; : e202400200, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955356

ABSTRACT

Ovarian cancer is among the most common gynecological cancers and the eighth leading cause of cancer-related deaths among women worldwide. Surgery is among the most important options for cancer treatment. During surgery, a biopsy is generally required to screen for lesions; however, traditional case examinations are time consuming and laborious and require extensive experience and knowledge from pathologists. Therefore, this study proposes a simple, fast, and label-free ovarian cancer diagnosis method that combines second harmonic generation (SHG) imaging and deep learning. Unstained fresh human ovarian tissues were subjected to SHG imaging and accurately characterized using the Pyramid Vision Transformer V2 (PVTv2) model. The results showed that the SHG imaged collagen fibers could quantify ovarian cancer. In addition, the PVTv2 model could accurately differentiate the 3240 SHG images obtained from our imaging collection into benign, normal, and malignant images, with a final accuracy of 98.4%. These results demonstrate the great potential of SHG imaging techniques combined with deep learning models for diagnosing the diseased ovarian tissues.

6.
J Clin Invest ; 134(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949024

ABSTRACT

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.


Subject(s)
Cilia , Kidney Diseases, Cystic , Leigh Disease , Mitochondria , Zebrafish , Humans , Zebrafish/metabolism , Zebrafish/genetics , Leigh Disease/genetics , Leigh Disease/metabolism , Leigh Disease/pathology , Cilia/metabolism , Cilia/pathology , Cilia/genetics , Animals , Mitochondria/metabolism , Mitochondria/pathology , Mitochondria/genetics , Kidney Diseases, Cystic/genetics , Kidney Diseases, Cystic/metabolism , Kidney Diseases, Cystic/pathology , Electron Transport Complex I/metabolism , Electron Transport Complex I/genetics , Armadillo Domain Proteins/metabolism , Armadillo Domain Proteins/genetics , Retina/metabolism , Retina/pathology , Retina/abnormalities , Eye Abnormalities/genetics , Eye Abnormalities/pathology , Eye Abnormalities/metabolism , Mice , Abnormalities, Multiple/genetics , Abnormalities, Multiple/metabolism , Abnormalities, Multiple/pathology , Cerebellum/metabolism , Cerebellum/pathology , Cerebellum/abnormalities , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Male
7.
iScience ; 27(6): 109880, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38952686

ABSTRACT

Amygdala serves as a highly cellular, heterogeneous brain region containing excitatory and inhibitory neurons and is involved in the dopamine and serotoninergic neuron systems. An increasing number of studies have revealed the underpinned mechanism mediating social hierarchy in mammal and vertebrate, however, there are rare studies conducted on how amygdala on social hierarchy in poultry. In this study, we conducted food competition tests and determined the social hierarchy of the rooster. We performed cross-species analysis with mammalian amygdala, and found that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided them into 10 main clusters, of which GABAergic and glutamatergic neurons were associated with social behaviors. In conclusion, our results provide to serve the developmental studies of the amygdala neuron system and new insights into the underpinned mechanism of social hierarchy in roosters.

8.
Diabetes Metab Syndr ; 18(6): 103068, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38959546

ABSTRACT

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

9.
Ren Fail ; 46(2): 2373272, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38967189

ABSTRACT

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.


Subject(s)
Exercise Therapy , Glomerular Filtration Rate , Network Meta-Analysis , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Exercise Therapy/methods , Risk Factors , Blood Pressure , Randomized Controlled Trials as Topic , Creatinine/blood , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism
10.
Article in Chinese | MEDLINE | ID: mdl-38973032

ABSTRACT

Objective:To investigate the changes in hearing threshold of the acquired primary cholesteatoma of the middle ear with different degrees of eustachian tube dysfunction after balloon eustachian tuboplasty. Methods:This retrospective study included forty cases with middle ear cholesteatoma and eustachian tube dysfunction who underwent open mastoidectomy + tympanoplasty + balloon eustachian tuboplasty were enrolled. All patients were admitted from November 2020 to April 2022. The preoperative eustachian tube score of 0-2 were defined as the lower group, and the scores of 3-5 were defined as the higher group. Pure tone audiometry was measured preoperatively and 1, 3, 6 and 12 months postoperatively. The average value of bone conduction threshold and air conduction threshold of 250-4 000 Hz were calculated, and the air-bone gap was calculated simultaneously. SPSS 25.0 was used for statistical analysis. P<0.05 was considered statistically significant. Results:In the lower group, the air conduction threshold and air-bone gap at 3 months postoperatively were significantly decreased in comparison with those preoperatively(P<0.05),as was the air-bone gap at 6 months postoperatively(P<0.05). In the higher group, the air conduction threshold and air-bone gap were significantly decreased at 3, 6 and 12 months postoperatively(P<0.05). Conclusion:The air conduction threshold and air-bone gap of patients with the acquired primary cholesteatoma of the middle ear and eustachian tube dysfunction were significantly decreased after eustachian tube balloon dilatation. Hearing improvement lasted longer in patients with slight eustachian tube dysfunction.


Subject(s)
Audiometry, Pure-Tone , Cholesteatoma, Middle Ear , Eustachian Tube , Tympanoplasty , Humans , Eustachian Tube/physiopathology , Eustachian Tube/surgery , Retrospective Studies , Female , Cholesteatoma, Middle Ear/surgery , Male , Tympanoplasty/methods , Adult , Middle Aged , Auditory Threshold , Mastoidectomy/methods , Bone Conduction
11.
Sci Total Environ ; 946: 174435, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964402

ABSTRACT

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

12.
Plants (Basel) ; 13(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38891302

ABSTRACT

Orobanche aegyptiaca Pers. is a holoparasitic plant that severely reduces tomato (Solanum lycopersicum L.) production in China. However, there is a lack of effective control methods and few known sources of genetic resistance. In this study, we focused on key genes in the JAZ family, comparing the JAZ family in Arabidopsis thaliana (L. Heynh.) to the tomato genome. After identifying the JAZ family members in S. lycopersicum, we performed chromosomal localization and linear analysis with phylogenetic relationship analysis of the JAZ family. We also analyzed the gene structure of the JAZ gene family members in tomato and the homology of the JAZ genes among the different species to study their relatedness. The key genes for O. aegyptiaca resistance were identified using VIGS (virus-induced gene silencing), and the parasitization rate of silenced tomato plants against O. aegyptiaca increased by 47.23-91.13%. The genes were localized in the nucleus by subcellular localization. Heterologous overexpression in A. thaliana showed that the key gene had a strong effect on the parasitization process of O. aegyptiaca, and the overexpression of the key gene reduced the parasitization rate of O. aegyptiaca 1.69-fold. Finally, it was found that the SLJAZ15 gene can positively regulate the hormone content in tomato plants and affect plant growth and development, further elucidating the function of this gene.

13.
Animals (Basel) ; 14(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38891594

ABSTRACT

Poultry studies conducted on Clostridium perfringens (CP) mainly focus on the effects of intestinal health and productive performance. Notably, the probiotic Bacillus amyloliquefaciens SC06 (BaSC06) is known to play a role in preventing bacterial infection. However, whether CP could induce the changes in brain function and behaviors and whether BaSC06 could play roles in these parameters is yet to be reported. The aim of this study was to evaluate the effects of BaSC06 on stress-related behaviors and gene expression, as well as the brain morphology and mRNA sequence of the hypothalamus in broiler chickens. A total of 288 one-day-old chicks were randomly divided into four groups: (1) a control group with no treatment administered or infection; (2) birds treated with the BaSC06 group; (3) a CP group; and (4) a BaSC06 plus CP (Ba_CP) group. The results showed that stress and fear-related behaviors were significantly induced by a CP infection and decreased due to the treatment of BaSC06. CP infection caused pathological damage to the pia and cortex of the brain, while BaSC06 showed a protective effect. CP significantly inhibited hypothalamic GABA and promoted HTR1A gene expression, while BaSC06 promoted GABA and decreased HTR1A gene expression. The different genes were nearly found between the comparisons of control vs. Ba group and Ba vs. CP group, while there were a great number of different genes between the comparisons of control vs. Ba_CP as well as CP vs. Ba_CP. Several different gene expression pathways were found that were related to disease, energy metabolism, and nervous system development. Our results will help to promote poultry welfare and health, as well as provide insights into probiotics to replace antibiotics and reduce resistance in the chicken industry.

14.
Food Res Int ; 189: 114533, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38876603

ABSTRACT

Glutinous rice is extensively consumed due to its nutritious content and wonderful flavor. However, glutinous rice flour has a high glycemic index, and the storage deterioration of sweet dumplingsissevere. Transglutaminase (TG) was used to cross-link glutinous rice protein and improve the characteristics of glutinous rice products. The findings demonstrated that TG significantly catalysed protein cross-linking to form a dense protein network, reduced the viscosity of glutinous rice paste and improved the thermal stability. The protein network may physically block the access of starch granules to digestive enzymes to lower the digestion rate of starch, and attenuate the damage of ice crystal molecules to the starch structure to improve the freezing stability of starch gels. The cracking rate and water loss of sweet dumplings prepared using glutinous rice flour with TG treated for 60 min reduced significantly. In conclusion, this study broadened the application of TG in starch products.


Subject(s)
Digestion , Flour , Food Handling , Oryza , Starch , Transglutaminases , Oryza/chemistry , Transglutaminases/metabolism , Starch/metabolism , Starch/chemistry , Flour/analysis , Food Handling/methods , Viscosity , Plant Proteins/metabolism , Plant Proteins/chemistry
15.
bioRxiv ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38895408

ABSTRACT

The development of motor control over sensory organs is a critical milestone in sensory processing, enabling active exploration and shaping of the sensory environment. However, whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we exploit the late onset of whisking behavior in mice to address this question in the somatosensory system. Using ex vivo electrophysiology, we discovered a transient increase in the intrinsic excitability of excitatory neurons in layer IV of the barrel cortex, which processes whisker input, precisely coinciding with the onset of active whisking at postnatal day 14 (P14). This increase in neuronal gain was specific to layer IV, independent of changes in synaptic strength, and required prior sensory experience. Strikingly, the effect was not observed in layer II/III of the barrel cortex or in the visual cortex upon eye opening, suggesting a unique interaction between the development of active sensing and the thalamocortical input layer in the somatosensory system. Predictive modeling indicated that changes in active membrane conductances alone could reliably distinguish P14 neurons in control but not whisker-deprived hemispheres. Our findings demonstrate an experience-dependent, lamina-specific refinement of neuronal excitability tightly linked to the emergence of active whisking. This transient increase in the gain of the thalamic input layer coincides with a critical period for synaptic plasticity in downstream layers, suggesting a role in facilitating cortical maturation and sensory processing. Together, our results provide evidence for a direct interaction between the development of motor control and sensory cortex, offering new insights into the experience-dependent development and refinement of sensory systems. These findings have broad implications for understanding the interplay between motor and sensory development, and how the mechanisms of perception cooperate with behavior.

16.
Cell Commun Signal ; 22(1): 307, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831315

ABSTRACT

BACKGROUND: Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in peripheral nociception remain unclear. METHODS: Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). RESULTS: IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. CONCLUSION: Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.


Subject(s)
Calcium Channels, T-Type , Cyclic AMP-Dependent Protein Kinases , Receptors, Interleukin , Sensory Receptor Cells , Signal Transduction , Trigeminal Ganglion , src-Family Kinases , Animals , Calcium Channels, T-Type/metabolism , Calcium Channels, T-Type/genetics , src-Family Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Trigeminal Ganglion/metabolism , Male , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/physiology , Receptors, Interleukin/metabolism , Mice , Mice, Inbred C57BL , Interleukins/metabolism
17.
Clin Lab ; 70(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38868872

ABSTRACT

BACKGROUND: Gastrointestinal infections present a significant public health concern as they lead to diverse clinical presentations and healthcare challenges. The rapid and accurate identification of causative pathogens is imperative for effective patient management. This study aimed to assess the clinical utility of the FilmArrayTM Gastrointestinal (GI) Panel for detecting gastrointestinal pathogens. METHODS: Between November 1, 2022, and December 31, 2023, we analysed gastrointestinal specimens collected from a cohort of patients aged 21 to 91 at Asia University Hospital. These specimens were analyzed using the FilmArrayTM GI Panel. RESULTS: The study included 76 patients for whom the FilmArrayTM GI assay was conducted, with 40 (52.6%) showing positive results. Among the positive specimens, 23 (57.5%) had a single pathogen, while the remaining 17 (42.5%) had multiple pathogens. The remaining 36 (47.4%) specimens showed no pathogens. The overall positivity rate of the specimens was 52.6%. The most frequently detected pathogens included Salmonella, Clostridium difficile (toxin A/B), and Enteropathogenic Escherichia coli (EPEC). CONCLUSIONS: This study underscores the clinical value of the FilmArrayTM GI assay as a rapid and reliable tool for diagnosing gastrointestinal infections. Its capacity to detect multiple pathogens simultaneously enhances diagnostic accuracy and gives information to use in clinical decision-making. We strongly recommend its integration into clinical practice to expedite the diagnosis and management of gastrointestinal infections, ultimately leading to improved patient care and healthcare efficiency.


Subject(s)
Gastrointestinal Diseases , Humans , Middle Aged , Aged , Adult , Female , Male , Aged, 80 and over , Young Adult , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/microbiology , Molecular Diagnostic Techniques/methods
18.
Bioorg Chem ; 149: 107500, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823310

ABSTRACT

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Discoidin Domain Receptor 1 , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors , Lung Neoplasms , Protein Kinase Inhibitors , Humans , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Discoidin Domain Receptor 1/antagonists & inhibitors , Discoidin Domain Receptor 1/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Animals , Molecular Structure , Mice , Drug Discovery , Mice, Nude , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Cell Line, Tumor , Mice, Inbred BALB C
19.
Article in English | MEDLINE | ID: mdl-38916705

ABSTRACT

With the social economy's rapid progress and the popularization of environmental awareness, ecological enterprises have gradually become a crucial trend in the development of modern enterprises. This work intends to promote the development of ecological enterprises to a higher level. This work first analyzes the management mode of ecological enterprises in the context of big data in China. Then, it establishes various indicators to analyze the role of sustainable technological innovation in enterprise development and the impact of digital empowerment on enterprise development. Finally, this work takes China's manufacturing industry and ecological enterprises in Hubei Province as examples to summarize the digital empowerment of sustainable technological innovation management of ecological enterprises under the background of big data. The final result indicates that sustainable technological innovation significantly reduces ecological enterprises' resource consumption and waste emissions. Additionally, it has a significant positive effect on improving enterprise output value and economic benefits. The digital empowerment of enterprises has a significant driving effect on sustainable technological innovation, with a digital driving coefficient of 26. This work provides a feasible scheme for the specific application of big data analysis in the technology innovation management of ecological enterprises, including market demand analysis, environmental monitoring and governance, technology assessment and risk management. This work expounds the role of big data analysis technology in improving decision-making efficiency, optimizing resource allocation and enhancing the competitiveness of enterprises in the digital empowerment of ecological enterprises.

20.
Clin Interv Aging ; 19: 1041-1050, 2024.
Article in English | MEDLINE | ID: mdl-38894884

ABSTRACT

Background: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer's disease continuum (ADC). Objective: This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC. Material and Methods: According to 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) standard, amyloid ß-protein positive (Aß+) and negative (Aß-) patients were recruited according to the Aß-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aß+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aß+ and 73 Aß- patients using a logistic regression analysis. Results: The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64-28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28-4.95). Conclusion: The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.


Subject(s)
Alzheimer Disease , Donepezil , Polymorphism, Single Nucleotide , Humans , Donepezil/therapeutic use , Alzheimer Disease/genetics , Alzheimer Disease/drug therapy , Female , Male , Aged , Aged, 80 and over , Genotype , Logistic Models , Cholinesterase Inhibitors/therapeutic use , Mental Status and Dementia Tests
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