Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.479
Filter
1.
J Environ Manage ; 362: 121308, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823301

ABSTRACT

Rural areas lacking essential sewage treatment facilities and collection systems often experience eutrophication due to elevated nutrient loads. Understanding nitrogen (N) sources and transport mechanisms in rural catchments is crucial for improving water quality and mitigating downstream export loads, particularly during storm events. To further elucidate the sources, pathways, and transport mechanisms of N from a rural catchment with intensive agricultural activities during storm events, we conducted an analysis of 21 events through continuous sampling over two rainy seasons in a small rural catchment from the lower reaches of the Yangtze River. The results revealed that ammonia-N (NH4+-N) and nitrate-N (NO3--N) exhibited distinct behaviors during rainstorm events, with NO3--N accounting for the primary nitrogen loss, its load being approximately forty times greater than that of NH4+-N. Through examinations of the concentration-discharge (c-Q) relationships, the findings revealed that, particularly in prolonged rainstorms, NH4+-N exhibited source limited pattern (b = -0.13, P < 0.01), while NO3--N displayed transport limited pattern (b = -0.21, P < 0.01). The figure-eight hysteresis pattern was prevalent for both NH4+-N and NO3--N (38.1% and 52.0%, respectively), arising from intricate interactions among diverse sources and pathways. For NO3--N, the hysteresis pattern shifted from clockwise under short-duration rainstorms to counter-clockwise under long-duration rainstorms, whereas hysteresis remained consistently clockwise for NH4+-N. The hysteresis analysis further suggests that the duration of rainstorms modifies hydrological connectivity, thereby influencing the transport processes of N. These insights provide valuable information for the development of targeted management strategies to reduce storm nutrient export in rural catchments.

3.
Curr Drug Deliv ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38812424

ABSTRACT

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

4.
Angew Chem Int Ed Engl ; : e202403333, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787684

ABSTRACT

Numerous studies have shown a fact that phase transformation and/or reconstruction are likely to occur and play crucial roles in electrochemical scenarios. Nevertheless, a decisive factor (such as facet, phase etc.) behind the diverse photoelectrochemical activity and selectivity of various copper/silicon photoelectrodes is still largely debated and missing in the community, especially for possibly dynamic behaviors of metal catalyst/semiconductor interface. Herein, through in situ X-ray absorption spectroscopy and transmission electron microscope, a model system of Cu nanocrystals with well-defined facets on black p-type silicon (BSi) is demonstrated to unprecedentedly reveal the dynamic phase transformation of forming irreversible silicide at Cu nanocrystal-BSi interface, which is validated to originate from the atomic interdiffusion between Cu and Si driven by light-induced dynamic activation process. The presence of in situ formed silicide can significantly enhance photovoltage and deliver a record-high onset potential above -0.4 V versus reversible reference electrode (RHE) for photoelectrochemical CH4 production. Significantly, the adaptive junction at Cu/Si interface is activated by an expansion of interatomic Cu-Cu distance, which efficiently restricts the C-C coupling pathway but strengthens the bonding with key intermediate of *CHO for CH4 yield, resulting in a remarkable 16-fold improvement in the product ratio of CH4/C2 products.

5.
J Transl Int Med ; 12(2): 177-187, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38779123

ABSTRACT

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

6.
Drug Des Devel Ther ; 18: 1613-1625, 2024.
Article in English | MEDLINE | ID: mdl-38774484

ABSTRACT

Purpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries. Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg-1), Group D (intranasal dexmedetomidine 2 mcg kg-1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS). Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010). Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation. Trial Registration: NCT04720963, January 22, 2021, ClinicalTrials.Gov.


Subject(s)
Administration, Intranasal , Anti-Anxiety Agents , Anxiety , Dexmedetomidine , Hypnotics and Sedatives , Humans , Dexmedetomidine/administration & dosage , Dexmedetomidine/pharmacology , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Male , Female , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/pharmacology , Child , Child, Preschool , Anxiety/drug therapy , Benzodiazepines/administration & dosage , Benzodiazepines/pharmacology , Double-Blind Method
7.
J Mater Chem B ; 12(22): 5391-5404, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38716492

ABSTRACT

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGsQur) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGsQur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo. Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGsQur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGsQur synthesized at 270 °C (CNGsQur270) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGsQur310) and 290 °C (CNGsQur290) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGsQur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGsQur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGsQur270 effectively delays and even prevents FeCl3-induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.


Subject(s)
Anticoagulants , Quercetin , Quercetin/chemistry , Quercetin/pharmacology , Anticoagulants/chemistry , Anticoagulants/pharmacology , Animals , Rats , Blood Coagulation/drug effects , Nanogels/chemistry , Humans , Mice , Male , Rats, Sprague-Dawley , Particle Size
8.
Clin Mol Hepatol ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38637957

ABSTRACT

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

9.
J Clin Transl Hepatol ; 12(4): 436-442, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38638382

ABSTRACT

Hepatic myelopathy (HM) is a rare neurological complication in the end stage of many liver diseases and is characterized by bilateral spastic paraparesis without sensory and sphincter dysfunction. It occurs owing to metabolic disorders and central nervous system dysfunction associated with cirrhosis. Without timely and effective clinical intervention, the prognosis of these patients is devastating. Although liver transplantation (LT) is an effective treatment for HM, the prognosis of these patients remains unsatisfactory. Early recognition and diagnosis of this disease are essential for improving patient prognosis. Here, we report a case of hepatitis B virus-associated decompensated cirrhosis with HM. The patient recovered well after LT. We also summarize the clinical characteristics and post-transplant outcomes of 25 patients with HM treated by LT through 2023, including this case.

10.
J Am Chem Soc ; 146(15): 10785-10797, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38573588

ABSTRACT

The anti-Stokes shift represents the capacity of photon upconversion to convert low-energy photons to high-energy photons. Although triplet exciton-mediated photon upconversion presents outstanding performance in solar energy harvesting, photoredox catalysis, stereoscopic 3D printing, and disease therapeutics, the interfacial multistep triplet exciton transfer leads to exciton energy loss to suppress the anti-Stokes shift. Here, we report near infrared-II (NIR-II) excitable triplet exciton-mediated photon upconversion using a hybrid photosensitizer consisting of lead sulfide quantum dots (PbS QDs) and new surface ligands of thiophene-substituted diketopyrrolopyrrole (Th-DPP). Under 1064 nm excitation, this photon upconversion revealed a record-corrected upconversion efficiency of 0.37% (normalized to 100%), with the anti-Stokes shift (1.07 eV) approaching the theoretical limit (1.17 eV). The observation of this unexpected result is due to our discovery of the presence of a weak interaction between the sulfur atom on Th-DPP and Pb2+ on the PbS QDs surface, facilitating electronic coupling between PbS QDs and Th-DPP, such that the realization of triplet exciton transfer efficiency is close to 100% even when the energy gap is as small as 0.04 eV. With this premise, this photon upconversion as a photocatalyst enables the production of standing organic gel via photopolymerization under 1064 nm illumination, displaying NIR-II photon-driven photoredox catalysis. This research not only establishes the foundation for enhancing the performance of NIR-II excitable photonic upconversion but also promotes its development in photonics and photoredox catalysis.

11.
Nat Astron ; 8(4): 504-519, 2024.
Article in English | MEDLINE | ID: mdl-38659610

ABSTRACT

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.

12.
Chem Biol Interact ; 394: 110987, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38574835

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 µM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 µM (C11) to 105.01 µM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 µM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase , Molecular Docking Simulation , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/chemistry , Animals , Humans , Rats , Structure-Activity Relationship , Membrane Proteins/metabolism , Fluorocarbons/chemistry , Fluorocarbons/metabolism , Fluorocarbons/pharmacology , Protein Binding , Carbon/chemistry , Carbon/metabolism , Binding Sites
13.
Pharmacol Res ; 203: 107164, 2024 May.
Article in English | MEDLINE | ID: mdl-38569981

ABSTRACT

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.


Subject(s)
Cardiovascular Diseases , Mitochondrial Proteins , Muscle Proteins , Humans , Animals , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/drug therapy , Muscle Proteins/metabolism , Muscle Proteins/genetics , Mitochondrial Proteins/metabolism , Mitochondria, Heart/metabolism , Mitochondria, Heart/drug effects
14.
Ultrasonics ; 140: 107315, 2024 May.
Article in English | MEDLINE | ID: mdl-38603903

ABSTRACT

Lung diseases are commonly diagnosed based on clinical pathological indications criteria and radiological imaging tools (e.g., X-rays and CT). During a pandemic like COVID-19, the use of ultrasound imaging devices has broadened for emergency examinations by taking their unique advantages such as portability, real-time detection, easy operation and no radiation. This provides a rapid, safe, and cost-effective imaging modality for screening lung diseases. However, the current pulmonary ultrasound diagnosis mainly relies on the subjective assessments of sonographers, which has high requirements for the operator's professional ability and clinical experience. In this study, we proposed an objective and quantifiable algorithm for the diagnosis of lung diseases that utilizes two-dimensional (2D) spectral features of ultrasound radiofrequency (RF) signals. The ultrasound data samples consisted of a set of RF signal frames, which were collected by professional sonographers. In each case, a region of interest of uniform size was delineated along the pleural line. The standard deviation curve of the 2D spatial spectrum was calculated and smoothed. A linear fit was applied to the high-frequency segment of the processed data curve, and the slope of the fitted line was defined as the frequency spectrum standard deviation slope (FSSDS). Based on the current data, the method exhibited a superior diagnostic sensitivity of 98% and an accuracy of 91% for the identification of lung diseases. The area under the curve obtained by the current method exceeded the results obtained that interpreted by professional sonographers, which indicated that the current method could provide strong support for the clinical ultrasound diagnosis of lung diseases.


Subject(s)
Algorithms , COVID-19 , Lung Diseases , Ultrasonography , Humans , Ultrasonography/methods , Lung Diseases/diagnostic imaging , COVID-19/diagnostic imaging , Lung/diagnostic imaging , Male , Female , Middle Aged , Image Interpretation, Computer-Assisted/methods , SARS-CoV-2
15.
Cancer Lett ; 590: 216842, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38582395

ABSTRACT

Platinum-based neoadjuvant therapy represented by cisplatin is widely employed in treating Triple-Negative Breast Cancer (TNBC), a particularly aggressive subtype of breast cancer. Nevertheless, the emergence of cisplatin resistance presents a formidable challenge to clinical chemotherapy efficacy. Herein, we revealed the critical role of tumor microenvironment (TME) derived exosomal miR-3960 and phosphorylation at the S16 site of PIMREG in activating NF-κB signaling pathway and promoting cisplatin resistance of TNBC. Detailed regulatory mechanisms revealed that SOD1-upregulated fibroblasts secrete miR-3960 and are then transported into TNBC cells via exosomes. Within TNBC cells, miR-3960 targets and inhibits the expression of BRSK2, an AMPK protein kinase family member. Furthermore, we emphasized that BRSK2 contributes to ubiquitination degradation of PIMREG and modulates subsequent activation of the NF-κB signaling pathway by mediating PIMREG phosphorylation at the S16 site, ultimately affects the cisplatin resistance of TNBC. In conclusion, our research demonstrated the crucial role of SOD1high fibroblast, exosomal miR-3960 and S16 site phosphorylated PIMREG in regulating the NF-κB signaling pathway and cisplatin resistance of TNBC. These findings provided significant potential as biomarkers for accurately diagnosing cisplatin-resistant TNBC patients and guiding chemotherapy strategy selection.


Subject(s)
Cisplatin , Drug Resistance, Neoplasm , Exosomes , MicroRNAs , Triple Negative Breast Neoplasms , Animals , Female , Humans , Mice , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cisplatin/pharmacology , Exosomes/metabolism , Exosomes/genetics , Fibroblasts/metabolism , Fibroblasts/drug effects , Gene Expression Regulation, Neoplastic/drug effects , MicroRNAs/genetics , MicroRNAs/metabolism , NF-kappa B/metabolism , NF-kappa B/genetics , Phosphorylation , Signal Transduction/drug effects , Superoxide Dismutase-1/genetics , Superoxide Dismutase-1/metabolism , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Tumor Microenvironment
16.
Infect Dis Ther ; 13(6): 1199-1213, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679663

ABSTRACT

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

17.
Br J Cancer ; 130(9): 1517-1528, 2024 May.
Article in English | MEDLINE | ID: mdl-38459187

ABSTRACT

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.


Subject(s)
Cell Proliferation , Colorectal Neoplasms , Disease Progression , Eukaryotic Initiation Factor-4A , Mice, Nude , MicroRNAs , RNA, Circular , beta Catenin , MicroRNAs/genetics , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , RNA, Circular/genetics , Animals , Mice , beta Catenin/metabolism , beta Catenin/genetics , Cell Proliferation/genetics , Eukaryotic Initiation Factor-4A/genetics , Eukaryotic Initiation Factor-4A/metabolism , Delta Catenin , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Male , Female , Cell Movement/genetics , Mice, Inbred BALB C
18.
Biomolecules ; 14(3)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38540790

ABSTRACT

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.


Subject(s)
Diatoms , Diatoms/genetics , Diatoms/metabolism , Spermidine Synthase/genetics , Spermidine Synthase/metabolism , Polyamines/metabolism , Biosynthetic Pathways , Genome
19.
Foods ; 13(6)2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38540844

ABSTRACT

Banana is a typical cold-sensitive fruit; it is prone to chilling injury (CI), resulting in a quality deterioration and commodity reduction. However, the molecular mechanism underlying CI development is unclear. In this study, cold storage (7 °C for 5 days) was used to induce CI symptoms in bananas. As compared with the control storage (22 °C for 5 days), cold storage increased the CI index and cell membrane permeability. Moreover, we found that the expression levels of the WRKY transcription factor MaWRKY70 were increased consistently with the progression of CI development. A subcellular localization assay revealed that MaWRKY70 was localized in the nucleus. Transcriptional activation analyses showed that MaWRKY70 processed a transactivation ability. Further, an electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter (DLR) assays showed that MaWRKY70 was directly bound to the W-box motifs in the promoters of four lipoxygenase (LOX) genes associated with membrane lipid degradation and activated their transcription. Collectively, these findings demonstrate that MaWRKY70 activates the transcription of MaLOXs, thereby acting as a possible positive modulator of postharvest CI development in banana fruit.

20.
Nat Prod Res ; : 1-11, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38498767

ABSTRACT

The chemical investigation of the fibrous roots of Ophiopogon japonicus afforded two new steroidal saponins, named ophiojaponin F (1) and ophiojaponin G (2), together with twelve known steroidal saponins (3-14) and ten known homoisoflavonoids (15-24). The structures of the isolated compounds were established unambiguously via spectroscopic analyses (NMR and HR-ESI-MS). Ophiojaponin F (1) is a 23-hydroxylated spirostanol saponin, and this type of steroidal saponin rarely been reported in liriopogons. All isolates were evaluated for their anti-pulmonary fibrosis activities on TGF-ß1-actived NIH3T3 cells for the first time. Among them, compounds 3, 4, 11-13, 15-19, 21 and 24 showed potential anti-pulmonary fibrosis effects with IC50 values ranging from 3.61 ± 0.86 µM to 21.33 ± 1.82 µM, and the main component ophiopogonin D (4) displayed the best activity with an IC50 value of 3.61 ± 0.86 µM. Thus, ophiopogonin D may be a potent candidate for the treatment of pulmonary fibrosis.

SELECTION OF CITATIONS
SEARCH DETAIL
...