The gonadotropin-releasing hormone （GnRH） and the gonadotropin hormone （GTH） play crucial roles in regulating the gonadal development of the vertebrate. In this study, the Gnrh2, Fshβ and Lhβ cDNAs ...were cloned and characterized in red crucian carp, triploids and tetraploids, and their phylogenetic relations were comparatively analyzed. All the Gnrh2 cDNAs in different ploidy fishes encoded proteins of 86 amino acids, which consisted of a signal peptide, a GnRH2 decapeptide and a GnRH-associated peptide （GAP） linked by a proteolytic cleavage site （Gly-Lys-Arg）. The GnRH2 decapeptide and proteolytic cleavage site were absolutely consistent among the three ploidy fishes, but the differences in signal peptide and GAP between diploids and tetraploids were fewer than those between diploids and triploids. It was presumed that the red crucian carp was the original maternal parent of tetraploids, so they had closer relationship. In addition, the Fshβ and Lhβ cDNAs of these three fishes encoded proteins of 130 and 140 amino acids, respectively. Compared with the molecules of other teleosts, the cysteine residues and potential glycosylation sites of Lhβ in these three fishes are fully conserved. However, most teleosts of Fshβ had 12 cysteine residues, while those of these three fishes were 13, and 12 of which might form six conserved disulfide bridges by utilizing the cleavage sites between the first and the second cysteine residues. Moreover, the lack of the second glycosylation site in Fshβ of these three fishes might influence the special structure and biological activities. On the other hand, the phylogenic tree analyses revealed that Gnrh2, Fshβ and Lhβ had similar phylogeny relationships among the cyprinids, which indicated that they were conserved in molecular structure and function during the evolution .
Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of ...this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness.
Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored.
IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects.
Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.
The development of enantioconvergent cross‐coupling of racemic alkyl halides directly with heteroarene C(sp2)−H bonds has been impeded by the use of a base at elevated temperature that leads to ...racemization. We herein report a copper(I)/cinchona‐alkaloid‐derived N,N,P‐ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)−H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α‐chiral alkylated azoles, such as 1,3,4‐oxadiazoles, oxazoles, and benzodoxazoles as well as 1,3,4‐triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)−H bond and the involvement of alkyl radical species under the reaction conditions.
The use of a cinchona‐alkaloid‐derived N,N,P‐ligand leads to the direct enantioconvergent coupling of racemic alkyl bromides with azole C(sp2)−H bonds by copper catalysis. The key to success is the ligand‐enabled facile oxidative addition at approximately room temperature that suppresses product racemization at elevated temperature. This method provides a range of enantioenriched α‐chiral alkylated azoles.
Abstract
Combining traditional textiles with triboelectric nanogenerators (TENGs) gives birth to self-powered electronic textiles (e-textiles). However, there are two bottlenecks in their widespread ...application, low power output and poor sensing capability. Herein, by means of the three-dimensional five-directional braided (3DB) structure, a TENG-based e-textile with the features of high flexibility, shape adaptability, structural integrity, cyclic washability, and superior mechanical stability, is designed for power and sensing. Due to the spatial frame-column structure formed between the outer braided yarn and inner axial yarn, the 3DB-TENG is also endowed with high compression resilience, enhanced power output, improved pressure sensitivity, and vibrational energy harvesting ability, which can power miniature wearable electronics and respond to tiny weight variations. Furthermore, an intelligent shoe and an identity recognition carpet are demonstrated to verify its performance. This study hopes to provide a new design concept for high-performance textile-based TENGs and expand their application scope in human-machine interfacing.
Making use of water wave energy at large is one of the most attractive, low‐carbon, and renewable ways to generate electric power. The emergence of triboelectric nanogenerator (TENG) provides a new ...approach for effectively harvesting such low‐frequency, irregular, and “random” energy. In this work, a TENG array consisting of spherical TENG units based on spring‐assisted multilayered structure is devised to scavenge water wave energy. The introduction of spring structure enhances the output performance of the spherical TENG by transforming low‐frequency water wave motions into high‐frequency vibrations, while the multilayered structure increases the space utilization, leading to a higher output of a spherical unit. Owing to its unique structure, the output current of one spherical TENG unit could reach 120 µA, which is two orders of magnitude larger than that of previous rolling spherical TENG, and a maximum output power up to 7.96 mW is realized as triggered by the water waves. The TENG array fabricated by integrating four units is demonstrated to successfully drive dozens of light‐emitting diodes and power an electronic thermometer. This study provides a new type of TENG device with improved performance toward large‐scale blue energy harvesting from the water waves.
Combining the advantages of spring structures and multilayered structures, a triboelectric nanogenerator (TENG) array consisting of four spherical TENGs with spring‐assisted multilayered structure for harvesting water wave energy is fabricated. Driven by the water waves, this TENG array produces a high output power of 15.97 mW, demonstrating the capacity for efficient water wave energy harvesting.
Recognizing renal vascular variants preoperatively is important in order to avoid vascular complications during surgery. This study aimed to investigate the renal vascular variants with dual-energy ...computed tomography (DECT) angiography to provide valuable information for surgery.
A total of 378 patients underwent DECT. The number, size, course and relationships of the renal vessels were retrospectively observed from the scans. Anomalies of renal arteries and veins were recorded and classified. Multiplanar reformations (MPR), maximum intensity projections (MIP), and volume renderings (VR) were used for analysis.
In 378 patients (756 kidneys), renal artery variations were discovered and recorded in 123 kidneys (16.3%, 123/756) of 106 patients (28.0%, 106/378). Type IB (early branches of the only one main renal artery) and IC (accessory renal artery with only one main renal artery) were found most frequently with an incidence of 11.4% (43/378) and 14.5% (55/378). The incidence of renal artery variations in the left kidney was not statistically different than in the right kidney (12.4% vs. 11.1%). The incidence of renal vein variations was detected in 104 patients (27.5%, 104/378). The incidence of venous variants in the right kidney was higher than in the left kidney (20.1% vs. 7.4%), but left renal vein variations were more complex. Variants of the left renal vein were detected in 28 patients including type 1 (circumaortic left renal vein) in eight cases, type 2 (retroaortic left renal vein) in seven cases, type 3 (abnormal reflux) in six cases, type 4 (late venous confluence of left renal vein) in five cases, and type 5 (rare type) in two cases. The frequency of left renal vein variation associated with the left renal accessory artery was significantly higher than with early branches of the left renal artery (P = 0.037).
The renal vascular variants are rather common and complex. DECT angiography can demonstrate the precise anatomy of the renal vessels, which is a benefit for renal transplantation or other renal operations.
Background and Aim
Chinese herbal medicine (CHM), as well as Western medicine (WM), is an important cause of drug‐induced liver injury (DILI). However, the differences between CHM and WM as agents ...implicated in liver injury have rarely been reported.
Methods
Overall, 1985 (2.05%) DILI cases were retrospectively collected from the 96 857 patients hospitalized because of liver dysfunction in the 302 Military Hospital between January 2009 and January 2014.
Results
In all the enrolled patients with DILI, CHM was implicated in 563 cases (28.4%), while 870 cases (43.8%) were caused by WM and the remaining patients (27.8%) by the combination of WM and CHM. Polygonum multiflorum was the major implicated CHM. Compared with WM, the cases caused by CHM showed more female (51 vs 71%, P < 0.001) and positive rechallenge (6.1 vs 8.9%, P = 0.046), a much greater proportion of hepatocellular injury (62.2 vs 88.5%, P < 0.001), and a higher mortality (2.8 vs 4.8%, P = 0.042); however, no differences in the rates of chronic DILI and ALF were found (12.9 vs 12.4%, P = 0.807; 7.6 vs 7.6%, P = 0.971). Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4 and 60.3%, all P < 0.001).
Conclusions
The causal relationship between CHM and liver injury is much complex, and the clinical characteristics of DILI caused by CHM differ from those caused by WM.
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
Aim： Previous study has shown that endometrial cancers with LKB1 inactivation are highly responsive to mTOR inhibitors. In this study we examined the effect of LKB1 gene status on mTOR inhibitor ...responses in non-small cell lung cancer （NSCLC） cells. Methods： Lung cancer cell lines Calu-1, H460, H1299, H1792, and A549 were treated with the mTOR inhibitors rapamycin or everolimus （RADO01）. The mTOR activity was evaluated by measuring the phosphorylation of 4EBP1 and S6K, the two primary mTOR substrates. Cells proliferation was measured by MTS or sulforhodamine B assays. Results： The basal level of mTOR activity in LKB1 mutant A549 and H460 cells was significantly higher than that in LKB1 wild-type Calu-1 and H1792 cells. However, the LKB1 mutant A549 and H460 cells were not more sensitive to the mTOR inhibitors than the LKB1 wild-type Calu-1 and H1792 cells. Moreover, knockdown of LKB1 gene in H1299 cells did not increase the sensitivity to the mTOR inhibitors. Treatment with rapamycin or RADO01 significantly increased the phosphorylation of AKT in both LKB1 wild-type and LKB1 mutant NSCLC cells, which was attenuated by the PI3K inhibitor LY294002. Furthermore, RADO01 combined with LY294002 markedly enhanced the growth inhibition on LKB1 wild-type H1792 cells and LKI31 mutant A549 cells. Conclusion： LKB1 gene inactivation in NSCLC cells does not increase the sensitivity to the mTOR inhibitors. The negative feedback activation of AKT by mTOR inhibition may contribute to the resistance of NSCLC cells to mTOR inhibitors.
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