To analyze the clinical characteristics and correlation of Fournier's gangrene induced by sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors, providing references for safe clinical drug use.
...The CNKI, WanFang, and PubMed databases were searched, and relevant documents were collected and statistically analyzed. The basic information of patients, drug use information, adverse reactions and outcomes were extracted and analyzed.
A total of 12 patients (8 males and 4 females) were included, with an average age of 55.6 years (ranging from 34 to 72 years). SGLT-2 inhibitors associated with Fournier's gangrene include empagliflozin (5 cases), dapagliflozin (5 cases), and canagliflozin (2 cases). Among them, 10 cases reported the time of first medication, ranging from 1 month to 6 years for the occurrence of adverse reactions. The most common concomitant drug was metformin (7 cases). Adverse reactions mainly manifested as redness, swelling and pain in the buttocks, perineum, perianal, scrotum and other positions, accompanied by an increased white blood cell count. Following surgery and antibiotic treatment, all patients showed improved.
Fournier's gangrene induced by SGLT-2 inhibitors is rare. If patients using SGLT-2 inhibitors are suspected of having Fournier's gangrene, it is recommended to discontinue the drugs immediately and initiate active treatment to ensure clinical safety.
Lignin can be an important source of synthetic commodity materials owing to its abundance in nature and low production cost. The current use of lignin as a raw material, however, is very limited and ...focused only on cheap and poorly defined nonfunctional materials. Herein we report a new lignin-containing functional polymer, lignin-graft-poly(5-acetylaminopentyl acrylate) (lignin-graft-PAA), which has been prepared by the covalent linkage of chemically modified lignin with PAA, which is an end-group functionalized polymer. This work makes two significant advances in the study of lignin-containing polymers: (1) lignin-graft-PAA is the first example of lignin being modified by a polymer with sophisticated structure, and (2) lignin-graft-PAA shows a special performance, autonomic self-healing properties, which have not yet been seen in lignin-containing polymers. The key synthetic step in this process utilizes a copper-catalyzed azide–alkyne cycloaddition or “click” reaction in order to join together the lignin and polymer moieties. The polymer, PAA, was itself prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization of monomers containing multiple hydrogen-bonding sites on their pendants in the form of acetylamino functional groups. The selected RAFT agents also resulted in a polymer with an azide group at its terminus, which is necessary for the desired click reaction. Separately, biomass lignin was chemically modified by 5-hexynoic acid to introduce an alkyne functionality onto lignin. The azide terminus of the polymer was joined to the alkyne group of lignin to form a covalent bond. The lignin-graft-PAA possesses a well-dispersed multiphase nanostructure, a rigid lignin phase and a soft-PAA phase, which has a rubber-like flexibility. The mechanical properties of the newly synthesized lignin-graft-PAA can be readily controlled by the mass ratio of lignin and polymer during synthesis. In this study, the mass ratio was varied by either polymer length or weight percentage of lignin. It was revealed that a lignin-graft-PAA composite with 15–20 wt % lignin demonstrated the most optimal rubber-like, flexible property. Thanks to the high degree of hydrogen bonding from the acetylamino functionalities, lignin-graft-PAA also showed self-healing properties, recovering up to 93% of its original maximum stress before fracture.
N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A ...methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined.
Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429.
KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3' UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3.
Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Mesozoic subduction history of the Paleo‐Pacific plate below the East Asian margin remains contentious, in part because the southern part is poorly understood. To address this, we conducted a ...sediment provenance study to constrain Mesozoic subduction history below West Sarawak, Borneo. A combination of detrital zircon U‐Pb geochronology, heavy minerals, trace element, and bulk rock Nd isotope data were used to identify the tectonic events. The overall maturity of mineral assemblages, dominantly felsic sources, abundant Precambrian‐aged zircons, and low εNd(0) values (average −13.07) seen in Late Triassic sedimentary rocks suggest a period of inactive subduction near Borneo. Slab shallowing subduction occurred between 200 and 170 Ma based on subdued magmatism and tectonic compression across West Sarawak. From c. 170 to 70 Ma there was widespread magmatism and we interpret the Paleo‐Pacific slab steepened. Collectively, we show the Paleo‐Pacific plate subduction had variable slab dip histories in Borneo.
Plain Language Summary
Modeling studies have shown that the ocean slab underwent periodic shallowing and steepening in the long‐term subduction system. To know the Mesozoic Paleo‐Pacific subduction history of the southern section, we established the subduction process of West Sarawak by studying the provenance of Mesozoic sedimentary rocks. Based on it, we subsequently deduce that west dipping subduction of the Paleo‐Pacific slab underwent periodic shallowing and steepening of slab dip from north to south.
Key Points
Triassic sediments in West Sarawak were mainly sourced from the craton erosion
Paleo‐Pacific slab underwent the Early Jurassic shallowing subduction, followed by slab steepening after the Middle Jurassic in West Borneo
The subduction of Paleo‐Pacific plate had variable slab dip histories from West Borneo to northeast China during the Mesozoic
A simple approach to polysubstituted thiophene derivatives is demonstrated. The synthesis is highlighted by the direct 2+2+1 cycloaddition reaction to construct carbon‐sulfur and carbon‐carbon bonds, ...without adding oxidizing, reducing and noble metal agents. All tested substrates provided their corresponding thiophene products in high isolated yields under the optimized conditions.
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•The purified fucoidan (CF) was confirmed to be highly sulfated and hyperbranched.•CF was molecularly dispersed in water to adopt sphere-like shape.•The desulfated derivative of CF ...was aggregated to form spherical shape in water.•CF showed significant anti-leukemia and antiangiogenic effects in vitro.•Ester sulfate groups in CF played an important role in exerting biological activity.
A fucoidan derived from marine brown algae has great potential in biomedical filed. Herein, the fucoidan was successfully isolated and purified by using chitosan microspheres, resulting in the sulfate fucoidan (CF) with degree of sulfation (DS) of 0.94. CF was identified to be highly branched, consisting of fucose (77.4%) and galactose (13.9%), etc., supported by the results of GCMS and light scattering with the structure-sensitive parameter of 0.98 in 0.15 M aqueous NaNO3. The individual CF and its desulfated derivative chains adopted sphere-like conformation in water, observed by atomic force microscopy. CF exhibited higher antiangiogenesis than the desulfated one and strong antileukemia activities through inhibiting cell proliferation and inducing cell apoptosis via cell cycle arrest at G1 phase in vitro. This work provided important information that ester sulfate groups of polysaccharide played an important role in the enhancing of bioactivities of fucoidan, and put forward to a potential drug to treat acute myelocytic leukemia (AML) and tumors.
Air pollution caused by particulate matter has significantly improved in China in recent years since the implementation of a series of stringent clean-air regulations. However, surface ozone ...concentrations have increased, especially in developed city clusters, such as the Beijing-Tianjin-Hebei, Yangtze River Delta, Pearl River Delta, and Sichuan Basin regions. Due to the complexity and nonlinearity of the ozone formation, accurately locating major sources of ozone and its precursors is an important basis for the formulation of cost-effective pollution control strategies. In this paper, the authors systematically summarize the reported results and outcomes of the methods and main conclusions of ozone source apportionment (regions and categories) in China from the published literature, based on observation-based methods and emission-based methods, respectively. The authors aim to provide a comprehensive understanding of ozone pollution and reliable references for the formulation of air pollution prevention policies in China.
The existence of intratumoral tertiary lymphoid structure (iTLS) has been reported to correlative with favorable clinical outcomes for patients with hepatocellular carcinoma (HCC). However, little is ...known about the role of peritumoral TLS (pTLS). This study aimed to investigate the prognostic role of pTLS either alone or jointly with iTLS and the potential association with local immune response in HCC. The formation and cellular composition of TLS was evaluated by hematoxylin & eosin and immunohistochemistry. Evaluation of tumor-infiltrating immune cells and formation of germinal center (GC) inside TLS was performed by immunohistochemistry. The gene expression profiles were analyzed by real-time PCR. In a total of 360 patients from two independent cohorts, the pTLS was identified in most, whereas iTLS could be observed in only approximately 30% of HCC specimens. Patients with high pTLS densities were associated with improved outcomes, those present with characteristic morphology of GC, particularly, showing an even better prognosis. The combination of pTLS and iTLS allowed the identification of patients with best prognosis. Tumors with high pTLS density showed significantly increased expression of Th1-, Th17- and immune suppression-related genes, as well as significantly higher infiltration of CD3+, CD8+ and CD20+ cells and lower infiltration of FOXP3+, CD68+ and PD1+ cells. Conclusively, we provide evidence that pTLS is associated with intratumoral immune infiltration, highlighting the dynamic interplay between pTLS and immune cells recruitment. High pTLS density links to a tumor microenvironment with an active immune reaction and improved patient survival and represents a promising prognostic biomarker for HCC.
Introduction
Thallium poisoning is a rare occurrence. Therefore, thallium poisoning is easily misdiagnosed and is often accompanied by a series of serious sequelae and can even result in death in ...severe cases. Here, we report long‐term follow‐up of a case of a patient who was poisoned with thallium on two separate occasions.
Methods
A 43‐year‐old man was initially misdiagnosed as gastroenteritis, diabetic peripheral neuropathy, and Guillain–Barré Syndrome (GBS) within 21 months. The correct diagnosis was confirmed by blood and urine thallium assays. After Prussian blue treatment, thallium was undetectable in the blood by day 60. Following this investigation, a criminal suspect confessed to two instances of adulterating thallium sulfate in the patient's beverage. A 6‐year follow‐up was performed after discharge, and a comprehensive literature was review.
Results
We found that the original gastrointestinal symptoms, skin lesions, and hair loss were reversed and had recovered, except for residual neurologic damage, even with long‐term rehabilitation.
Discussion
Thallium intoxication may have been initially identified if neurologic symptoms had occurred concurrently with gastrointestinal and cutaneous symptoms. Neurologic damage represented the main sequelae of thallium poisoning in our present case report.
Thallium poisoning; neurologic outcome; neuroelectrophysiology
Abstract Objective Our objective was to investigate a miRNA pathway that acts downstream of VEGF-induced invasion of ovarian cancer cells. Method We used two paired high and low metastatic serous ...ovarian cancer cells to demonstrate the role of miR-205 in VEGF-induced invasion of ovarian cancer cells and to investigate the gene targets of miR-205. Results Our previous comparative proteomics studies showed that VEGF decreased the expression of Ezrin and Lamin A/C, and this result was validated in the present study using qPCR and Western blotting. Then we found that VEGF enhanced the invasiveness of and inhibited apoptosis in ovarian cancer cells as assessed by transwell invasion assays and Annexin V-FITC immunostaining, respectively. VEGFR was also expressed in ovarian cancer cells, as assessed by immunocytochemical staining. Furthermore, using the dual-luciferase report assay system, we demonstrated that miR-205 targeted Ezrin and Lamin A/C. MiR-205 was up-regulated in ovarian cancer cells exposed to VEGF, as determined by miRNA microarray analysis and verified by qPCR. MiR-205 promoted the invasion and proliferation of ovarian cancer cells. Conclusion Our data reveal a new potential pathway in which VEGF promotes the invasion of ovarian cancer cells, partially via the down-regulation of Ezrin and Lamin A/C caused by increased expression of miR-205.
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