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Two fenestrindane‐based porous nanographenes containing four polyaromatic macrocycles in a highly twisted, basically S4–symmetric conformation were synthesized and characterized by NMR spectroscopy and mass spectrometry. Stepwise π‐extension at the periphery of the fenestrindane core by a sequence of eightfold Suzuki‐Miyaura cross‐coupling, fourfold Scholl cyclodehydrogenation and another eightfold Suzuki‐Miyaura reaction affords the porous nanographene precursors in good yields. In the last step, fourfold intramolecular Yamamoto coupling generates the porous nanographenes in 17‐18 %‐yield. Their optical and electronic properties were studied by UV/Vis and fluorescence spectroscopy and cyclic voltammetry. DFT calculations revealed structural details of the macrocycles. The surprisingly weak binding of these porous structures with chloride ions (K≈10 M−1) is attributed to their highly twisted conformation. The title compounds represent the first porous nanographenes based on the [5.5.5.5]fenestrane motif and, at the same time, they consist of a fenestrane‐like polyarylene network. [ABSTRACT FROM AUTHOR]

In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with 3 wk of hypoxia (Hx). In addition, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared with Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared with PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP. NEW & NOTEWORTHY: We attempted to establish a mouse model of severe and irreversible pulmonary hypertension by substituting hypoxia with pulmonary overcirculation. To do so, we treated mice with either SU5416 or monocrotaline pyrrole after pneumonectomy and performed hemodynamic evaluations for PH. Despite this "two-hit" protocol, mice did not exhibit signs of severe pulmonary hypertension or exacerbated pulmonary vascular remodeling compared with PNx alone. [ABSTRACT FROM AUTHOR]

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp. [ABSTRACT FROM AUTHOR]

Hyperspectral imaging (HSI) has been applied to assess the texture profile analysis (TPA) of processed meat. However, whether the texture profiles of live fish muscle could be assessed using HSI has not been determined. In this study, we evaluated the texture profile of four muscle regions of live common carp by scanning the corresponding skin regions using HSI. We collected skin hyperspectral information from four regions of 387 scaled and live common carp. Eight texture indicators of the muscle corresponding to each skin region were measured. With the skin HSI of live common carp, six machine learning (ML) models were used to predict the muscle texture indicators. Backpropagation artificial neural network (BP-ANN), partial least-square regression (PLSR), and least-square support vector machine (LS-SVM) were identified as the optimal models for predicting the texture parameters of the dorsal (coefficients of determination for prediction (rp) ranged from 0.9191 to 0.9847, and the root-mean-square error for prediction ranged from 0.1070 to 0.3165), pectoral (rp ranged from 0.9033 to 0.9574, and RMSEP ranged from 0.2285 to 0.3930), abdominal (rp ranged from 0.9070 to 0.9776, and RMSEP ranged from 0.1649 to 0.3601), and gluteal (rp ranged from 0.8726 to 0.9768, and RMSEP ranged from 0.1804 to 0.3938) regions. The optimal ML models and skin HSI data were employed to generate visual prediction maps of TPA values in common carp muscles. These results demonstrated that skin HSI and the optimal models can be used to rapidly and accurately determine the texture qualities of different muscle regions in common carp. [ABSTRACT FROM AUTHOR]

Highly unsaturated fatty acids (HUFAs) are essential for mammalian health, development and growth. However, most mammals, including humans, are incapable of synthesizing n-6 and n-3 HUFAs. Fish can convert C18 unsaturated fatty acids into n-6 and n-3 HUFAs via fatty acid desaturase (Fads), in which Fads2 is a key enzyme in HUFA biosynthesis. The allo-tetraploid common carp theoretically encode two duplicated fads2 genes. The expression patterns and desaturase functions of these two homologous genes are still unknown. In this study, the full length of the fads2a and fads2b were identified in common carp (Cyprinus carpio). Expression analyses indicate that both genes were mainly expressed in the liver and the expression of fads2b is higher than fads2a at different developmental stages in carp embryos. Heterogenous expression and 3D docking analyses suggested that Fads2b demonstrated stronger ∆6 and ∆5 desaturase activities than Fads2a. The core promotor regions of fads2a and fads2b were characterized and found to have different potential transcriptional binding sites. These results revealed the same desaturase functions, but different activities of two homologues of fasd2 genes in common carp. The data showed that fads2b played a more important role in HUFA synthesis through both expression and functional analyses. [ABSTRACT FROM AUTHOR]

1,5,9‐Tribromo‐2,3,6,7,10,11‐hexamethoxy‐4b1‐methyltribenzotriquinacene, a C3‐symmetric TBTQ derivative, can be prepared conveniently and with high regioselectivity from readily available starting materials. It is a versatile key compound for the synthesis of other chiral 1,5,9‐trifunctionalized TBTQ derivatives and π‐extended congeners in which the bays of the TBTQ skeleton are bridged by vinylene and 1,2‐arylene units. X‐ray crystal structure analysis and UV‐vis spectroscopy show that vinylene bay‐bridging enables better π‐conjugation with the arene rings of the TBTQ core than 1,2‐arylene bay‐bridging does. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to evaluate primary treatment and recent survival trends in patients with primary diffuse large B‐cell lymphoma of central nervous system (CNS) from 1995 to 2016. Using the SEER data, patients diagnosed with non‐HIV‐associated primary central nervous system lymphoma (PCNSL)–diffuse large B‐cell lymphoma (DLBCL) aged ⩾18 years between 1995 and 2016 were identified. The year of diagnosis was divided into the time period‐1 (1995–2002), the time period‐2 (2003–2012), and the time period‐3 (2013–2016). Chi‐square tests, the Kaplan–Meier method, log‐rank test, and Cox regression model were used in the analysis. Overall, 3760 patients were included. Both the use of radiotherapy alone and the application of combined chemoradiotherapy decreased significantly, following the wider use of chemotherapy alone during 1995–2016. There was a significant improvement in PCNSL cause‐specific survival (CSS) (period‐1: 13 months vs. period‐2: 19 months vs. period‐3: 41 months, p < 0.001). Survival of patients aged above 70 years did not change from the time period‐1 to the time period‐2 (p = 0.101). However, there was an increase in CSS from the time period‐2 to the time period‐3 in the elderly patients (period‐2: 5 months vs. period‐3: 9 months, p < 0.001). On multivariable analyses, diagnosed in the time period‐3 was significantly and independently associated with better CSS (hazard ratio 0.577, 95% confidence interval 0.506–0.659, p < 0.001). Our analysis shows the use of radiotherapy in the treatment of PCNSL has waned over the study span. There was a significant improvement in CSS during 1995–2016, which reflected developments in treatment over time. The elderly patient population also gained a significant CSS benefit in the most recent period. [ABSTRACT FROM AUTHOR]

Simple Summary: Fish is an important PUFA source for human diet. Much research has focused on increasing the PUFA products of fish. Improving the biosynthesis of PUFAs would also be a way to contribute to nutrition supplement for human health. Aquaculture selective breeding by genetic markers is essential for increasing the content of PUFAs. Fatty acid desaturase 2 (fads2) and elongase 5 (elovl5) have been proven key rate-limiting enzymes in the synthesis of PUFAs for bony fishes. These genes' coding SNPs (cSNPs) were reported to be significantly associated with the PUFA contents in common carp. However, the promoter SNPs (pSNPs) effectiveness for the PUFA contents has not been evaluated yet. This study identified the genetic variants in the promoter regions of fads2a/2b and elovl5a/5b. Moreover, the joint effects of multiple cSNPs and pSNPs in fads2b and elovl5b, two major genes related to the PUFA biosynthesis, were evidenced by the higher explained percentages of phenotype. Furthermore, the gene expression level of fads2a and fads2b showed significant positive correlation with the contents of multiple PUFAs. These SNPs would be potential markers for future selection to improve the PUFA contents in common carp. The allo-tetraploid common carp encodes two duplicated fads2 genes (fads2a and fads2b) and two duplicated elovl5 genes (elovl5a and elovl5b). The coding SNPs (cSNPs) of these genes were reported to be significantly associated with the PUFA contents. Whether the promoter SNPs (pSNPs) were associated with the PUFA contents has not been reported yet. In this study, after sequencing the promoters of these four genes, we identified six pSNPs associated with the contents of PUFAs in common carp, including one elovl5a pSNP, one elovl5b pSNP, and four fads2b pSNPs. The pSNPs were predicted in the locations of transcriptional factor binding sites. Together with previously identified cSNPs in fads2b and elovl5b, the pSNPs and cSNPs of these two genes had the joint effects on the PUFA contents with higher explained percentage of phenotypic variation of the PUFA contents than single gene. The expression levels of both fads2a and fads2b were significantly positively correlated with the contents of six PUFAs. The fads2b pSNPs corresponding to higher fads2b expression levels were associated with higher PUFA contents. The pSNPs and cSNPs will be useful for the future selection breeding of common carp with higher PUFA contents. [ABSTRACT FROM AUTHOR]

Most diploid freshwater and marine fish encode one elovl5 elongase, having substrate specificity and activities towards C18, C20 and C22 polyunsaturated fatty acids (PUFAs). The allo-tetraploid common carp is hypothesized to encode two duplicated elovl5 genes. How these two elovl5 genes adapt to coordinate the PUFA biosynthesis through elongase function and expression divergence requires elucidation. In this study, we obtained the full-length cDNA sequences of two elovl5 genes in common carp, named as elovl5a and elovl5b. Functional characterization showed that both enzymes had elongase activity towards C18, C20 and C22 PUFAs. Especially, the activities of these two enzymes towards C22 PUFAs ranged from 3.87% to 8.24%, higher than those in most freshwater and marine fish. The Elovl5a had higher elongase activities than Elovl5b towards seven substrates. The spatial-temporal expression showed that both genes co-transcribed in all tissues and development stages. However, the expression levels of elovl5b were significantly higher than those of elovl5a in all examined conditions, suggesting that elovl5b would be the dominantly expressed gene. These two genes had different potential transcriptional binding sites. These results revealed the complicated roles of elovl5 on PUFA synthesis in common carp. The data also increased the knowledge of co-ordination between two homoeologs of the polyploid fish through function and expression divergence. [ABSTRACT FROM AUTHOR]

Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: PUFAs have an essential impact on human health, but their availability constitutes a critical bottleneck in food production. Although fish is the traditional source of PUFAs, it is limited by the stagnation of fisheries. Many studies aim to increase the PUFA products of fish. Genetic markers are efficient in aquaculture breeding. Fatty acid desaturase 2 (fads2) and elongase 5 (elovl5) are the rate-limiting enzymes in the synthesis of PUFAs. The allo-tetraploid common carp is able to biosynthesize endogenous PUFAs. However, selective breeding common carp with high PUFA contents was hindered due to a lack of effective molecular markers. For future breeding common carp capable of producing endogenous PUFAs more effectively, we previously identified the polymorphisms in the coding regions of two duplicated fads2, fads2a and fads2b. However, the polymorphisms in the duplicated elovl5, elovl5a and elovl5b, were not detected. This study screened the genetic variants in the coding regions of elovl5a and elovl5b. Moreover, the joint effects of multiple coding SNPs in fads2b and elovl5b, two major genes regulating the PUFA biosynthesis, were evidenced with the increased explained percentages of the PUFA contents. These polymorphisms in these two genes were used to evaluate the breeding values of PUFAs. These SNPs would be potential markers for future selection to improve the PUFA contents in common carp. The allo-tetraploid common carp, one widely cultured food fish, is able to produce poly-unsaturated fatty acids (PUFAs). The genetic markers on the PUFA contents for breeding was limited. The polymorphisms in elovl5a and elovl5b, the rate-limiting enzymes in the PUFA biosynthesis, have not been investigated yet. Herein, we identified one coding SNP (cSNP) in elovl5a associated with the content of one PUFA and two cSNPs in elovl5b with the contents of eight PUFAs. The heterozygous genotypes in these three loci were associated with higher contents than the homozygotes. Together with previously identified two associated cSNPs in fads2b, we found the joint effect of these four cSNPs in fads2b and elovl5b on the PUFA contents with the increased explained percentages of PUFA contents. The genotype combinations of more heterozygotes were associated with higher PUFA contents than the other combinations. Using ten genomic selection programs with all cSNPs in fads2b and elovl5b, we obtained the high and positive correlations between the phenotypes and the estimated breeding values of eight PUFAs. These results suggested that elovl5b might be the major gene corresponding to common carp PUFA contents compared with elovl5a. The cSNP combinations in fads2b and elovl5b and the optimal genomic selection program will be used in the future selection breeding to improve the PUFA contents of common carp. [ABSTRACT FROM AUTHOR]

Simple Summary: Many widely cultured freshwater fish species, such as common carp, belong to the Cyprinidae family. However, most cyprinids have numerous and complex intermuscular bones (IBs), resulting in an adverse effect on cyprinid fish meat processing and consumption. Numerous studies have been trying to understand the development mechanism of IBs and to identify the SNPs associated with the total IB number. However, the SNPs associated with different forms of IBs have been studied less thoroughly. The joint effects of the SNPs on IB development also remain poorly understood. The common carp has numerous geographical populations and domesticated strains, diversifying its phenotypes. The question of whether consensus IB-related SNPs or genes exist among multiple strains of common carp has also not yet been answered. Selective breeding of IB-reduced common carp has been hindered due to a lack of effective molecular markers. To answer these questions, we performed bulked segregant analysis (BSA) to detect the consensus SNPs in three strains. The consensus BSA-SNPs and the other SNPs in their flanking regions were validated in additional individuals. The SNPs associated with the frequency of different IB types were identified. We examined the joint effects of significant SNPs on the numbers of different types of IBs. The identified genetic markers may benefit future selective breeding and reduce the IB number in common carp. The allotetraploid common carp is one of the most important freshwater food fish. However, the IBs found in allotetraploid common carp increase the difficulty in fish meat processing and consumption. Although candidate genes associated with the total IB number have been identified, the SNPs associated with the numbers of the total IBs and different forms of IBs have not yet been identified, hindering the breeding of IB-reduced common carp. Herein, the numbers of different types of IBs in three common carp strains were measured. Using whole-genome resequencing and bulked segregant analysis in three pairs of IB-more and IB-less groups, we identified the consensus nonsynonymous SNPs in three strains of common carp. Screening the flanking regions of these SNPs led to the detection of other SNPs. Association study detected 21 SNPs significantly associated with the number of total IBs, epineural-IBs, and ten detailed types of IBs. We observed the joint effects of multiple SNPs on each associated IB number with an improved explained percentage of phenotypic variation. The resulting dataset provides a resource to understand the molecular mechanisms of IB development in different common carp strains. These SNPs are potential markers for future selection to generate IB-reduced common carp. [ABSTRACT FROM AUTHOR]

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance. [ABSTRACT FROM AUTHOR]

The East Asian subtropical westerly jet (EASWJ) is one of the most important factors modulating the Meiyu rainfall in the Yangtze-Huaihe River Basin, China. This article analyzed periods of the medium-term EASWJ variation, wave packet distribution and energy propagation of Rossby waves along the EASWJ during Meiyu season, and investigated their possible influence on abnormal Meiyu rain. The results showed that during the medium-term scale atmospheric dynamic process, the evolution of the EASWJ in Meiyu season was mainly characterized by the changes of 3-8 d synoptic-scale and 10-15 d low-frequency Rossby waves. The strong perturbation wave packet and energy propagation of the 3-8 d synoptic-scale and 10-15 d low-frequency Rossby waves are mostly concentrated in the East Asian region of 90°-150°E, where the two wave trains of perturbation wave packets and wave-activity flux divergence coexist in zonal and meridional directions, and converge on the EASWJ. Besides, the wave trains of perturbation wave packet and wave-activity flux divergence in wet Meiyu years are more systematically westward than those in dry Meiyu years, and they are shown in the inverse phases between each other. In wet (dry) Meiyu year, the perturbation wave packet high-value area of the 10-15 d low-frequency variability is located between the Aral Sea and the Lake Balkhash (in the northeastern part of China), while over eastern China the wave-activity flux is convergent and strong (divergent and weak), and the high-level jets are strong and southward (weak and northward). Because of the coupling of high and low level atmosphere and high-level strong (weak) divergence on the south side of the jet over the Yangtze-Huaihe River Basin, the low-level southwest wind and vertically ascending motion are strengthened (weakened), which is (is not) conducive to precipitation increase in the Yangtze-Huaihe River Basin. These findings would help to better understand the impact mechanisms of the EASWJ activities on abnormal Meiyu from the perspective of medium-term scale Rossby wave energy propagation. [ABSTRACT FROM AUTHOR]

The article offers information on the translational research that is essential to develop strategies for the treatment of pulmonary arterial hypertension (PAH) using animal models that reproduce the severity. It mentions that expiratory chest Computed tomography (CT) lung images must be interpreted with caution; and also mentions the absence of hypoxia, can produce an emphysema-like lung phenotype.

Background: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB). Methods: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses. Results: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats. Conclusion: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle. [ABSTRACT FROM AUTHOR]

Patients with Non‐Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP‐16) alone and that of MCC using both VP‐16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI‐LY‐10 and SU‐DHL‐6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low‐dose VP‐16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP‐16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy‐related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP‐16 48 hours + RAD001 24 hours is the optimal method for treating NHL. [ABSTRACT FROM AUTHOR]

Objectives: Total flavones of Rhododendron simsii Planch flower (TFR) are an effective part extracted from the flower. The present study was designed to investigate the protective effect of TFR in isolated rat heart following global ischaemia‐reperfusion and the possible underlying mechanisms. Methods: Langendorff perfusion apparatus was used to perfuse isolated rat heart which was subjected to global ischaemia‐reperfusion. The hemodynamic parameters were continuously monitored. Coronary flow as well as lactate dehydrogenase (LDH), creatine phosphokinase‐MB (CK‐MB) and cardiac troponin I (cTnI) in coronary effluents was measured. RhoA activity and urotensin receptor (UTR) and Rho‐related coiled‐coil‐forming protein kinase (ROCK) protein expressions in rat myocardium were examined, respectively. Cardiac dysfunction was indicated by the alterations of hemodynamic parameters and the reduced coronary flow. Key findings: Total flavones of Rhododendron simsii Planch flower significantly improved ischaemia‐reperfusion–induced cardiac dysfunction and leakages of LDH, CK‐MB and cTnI, and inhibited myocardial ischaemia‐reperfusion–increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. The improvement of TFR in the cardiac dysfunction and the leakage of LDH, CK‐MB and cTnI were markedly attenuated under the UTR blockade and ROCK inhibition. TFR‐inhibited RhoA activity was decreased under the UTR blockade. Conclusions: Total flavones of Rhododendron simsii Planch flower had a protective effect on ischaemia‐reperfusion injury in isolated rat heart, which may be attributed to the blocking of UTR and subsequent inhibition of the RhoA‐ROCK pathway. [ABSTRACT FROM AUTHOR]

Prostate cancer is a common visceral cancer of men worldwide. It is important to develop a more effective treatment for prostate cancer to overcome the treatment resistance that occurs with recurrence. RNA interference has been demonstrated to be a powerful tool for gene knockdown and has potential as a cancer treatment. It has been previously demonstrated that staining of special AT‑rich sequence‑binding protein 1 (SATB1) was stronger in prostatic carcinoma with metastasis compared with prostatic carcinoma without metastasis. In the present study, SATB1 small interfering (si)RNA was transfected into prostate cancer DU145 cells and normal human lung fibroblast cells, and cell proliferation was investigated using a Cell Counting kit‑8. Three siRNA were transfected into cells using siPORT Lipid Transfection agent, and blank control and negative control groups were established. The cells were harvested and SATB1 mRNA and protein expression was determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. DU145 cell adhesion, migration and invasion capabilities were determined using cell adhesion, Transwell and Transwell with Matrigel assays, respectively. Silencing SATB1 significantly inhibited DU145 cell growth, adhesion, migration and invasive capability in vitro, indicating that a SATB1‑targeting siRNA was successfully engineered. The results of the present study suggest that SATB1 siRNA may be a potential agent for treating human prostate cancer. [ABSTRACT FROM AUTHOR]

Emergency rescue material reserves are vital for the success of emergency rescue activities. In this study, we consider a situation where a government owned distribution center and framework agreement suppliers jointly store emergency rescue materials. Using a scenario-based approach to represent demand uncertainty, we propose a comprehensive transportation pattern for the following supply chain: “suppliers—government distribution center—disaster area.” Using a joint reserves model that includes the government and framework agreement suppliers, we develop a non-linear mathematic model that determines the choices of the framework suppliers, the corresponding optimal commitment quantities, and the quantity of materials that are stored at a government distribution center. Finally, we use IBM ILOG CPLEX to solve the numerical examples to verify the effectiveness of the mode and perform sensitivity analyses on the relevant parameters. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown Kinesin family member 20A (KIF20A) may play a critical role in the development and progression of cancer. However, the clinical value of KIF20A in nasopharyngeal carcinoma (NPC) is unknown. Here, we investigated the expression pattern of KIF20A in NPC and its correlation with clinicopathological features of patients. Methods: Real-time PCR and Western blotting were used to quantify KIF20A expression in NPC cell lines and clinical specimens compared with normal controls. KIF20A protein expression was also examined in archived paraffin embedded tumor samples from 105 patients with pathologically confirmed NPC by immunohistochemistry (IHC). Statistical analyses were applied to assess the associations between KIF20A expression and the clinicopathological features and survival outcomes. Effects on migration and invasion were assessed by wound healing and transwell invasion assays after KIF20A silencing. Results: KIF20A was significantly overexpressed at both the mRNA and protein levels in NPC cell lines and human tumor tissues. 45/105 (42.9%) of NPC specimens expressed high levels of KIF20A among the KIF20A detectable cases. Statistical analysis revealed that high KIF20A expression was significantly associated with gender (P = 0.046), clinical stage (P<0.001), T category (P = 0.022), N category (P<0.001), distant metastasis (P = 0.001) and vital status (P = 0.001). Moreover, Higher KIF20A expression patients had shorter overall survival (OS) and progression-free survival (PFS) (P = 0.001 and P = 0.001; log-rank test). In multivariate analysis, KIF20A was an independent prognostic factor for OS and PFS in the entire cohort (P = 0.033, P = 0.008). Knock down of KIF20A expression significantly suppressed NPC cell’s migration and invasion. Conclusions: KIF20A is overexpressed and may serve as an independent prognostic biomarker in NPC. Targeting KIF20A reduces migration and invasion of NPC cells. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility and safety of the closed technique (CT) with Veress needle for the creation of retroperitoneal working space (RWS) for the retroperitoneoscopic ablation of symptomatic renal cysts by comparison with the open technique (OT). Material and methods: In this series of 412 patients who underwent retroperitoneoscopic ablation of symptomatic renal cysts, RWS was created by OT in 231 patients and CT in 181 patients, respectively. The time to create RWS, operative time, and complications were analyzed. Results: Creation of RWS and retroperitoneoscopic cyst ablation were completed successfully in all cases. The time to create RWS by CT was significantly shorter than that by OT (6.4 ± 1.2 vs 9.6 ± 1.2 min, P< 0.01). The operative time was shorter with CT than with OT (50.5 ± 6.5 vs 52.5 ± 6.7 min, P< 0.01). Subcutaneous emphysema developed in five (2.16%) of 231 patients undergoing OT and one (0.55%) of 181 patients undergoing CT. Port-site gas leakage was observed in six patients undergoing OT. Conclusions: Our study shows that CT with Veress needle for the creation of RWS for symptomatic renal cysts is feasible and safe in experienced hands, reducing troublesome port-site gas leakage and subcutaneous emphysema. [ABSTRACT FROM AUTHOR]

Simple Summary: Fishes are the major dietary source of polyunsaturated fatty acids (PUFAs) for humans. The limited availability of PUFAs derived from fish represents a critical bottleneck in food production systems, one that numerous research institutions and aqua-feed companies in this field are trying to overcome. This problem could be minimized by select-bred fish to be capable of more effectively producing endogenous PUFAs. Fatty acid desaturase 2 (fads2) is one of the rate-limiting enzymes in the synthesis of PUFAs. The common carp, one of the most important food and ornamental allo-tetraploid fish, encodes two fads2 genes (fads2a and fads2b). The PUFA contents among common carp individuals were numerous, suggesting that there might exist polymorphisms in fads2a and fads2b. However, selective breeding of common carp with high PUFA contents was hindered due to a lack of effective molecular markers. This study investigated the contents of PUFAs in common carp and identified polymorphisms in the CDS regions of fads2a and fads2b. The association study identified three cSNPs associated with the PUFA contents and suggested that fads2b might be the major gene responding for common carp PUFA contents. These cSNPs would be potential markers for future selection to improve the PUFA contents in common carp. Fatty acid desaturase 2 (fads2) is one of the rate-limiting enzymes in PUFAs biosynthesis. Compared with the diploid fish encoding one fads2, the allo-tetraploid common carp, one most important food fish, encodes two fads2 genes (fads2a and fads2b). The associations between the contents of different PUFAs and the polymorphisms of fads2a and fads2b have not been studied. The contents of 12 PUFAs in common carp individuals were measured, and the polymorphisms in the coding sequences of fads2a and fads2b were screened. We identified five coding single nucleotide polymorphisms (cSNPs) in fads2a and eleven cSNPs in fads2b. Using the mixed linear model and analysis of variance, a synonymous fads2a cSNP was significantly associated with the content of C20:3n-6. One non-synonymous fads2b cSNP (fads2b.751) and one synonymous fads2b cSNP (fads2b.1197) were associated with the contents of seven PUFAs and the contents of six PUFAs, respectively. The heterozygous genotypes in both loci were associated with higher contents than the homozygous genotypes. The fads2b.751 genotype explained more phenotype variation than the fads2b.1197 genotype. These two SNPs were distributed in one haplotype block and associated with the contents of five common PUFAs. These results suggested that fads2b might be the major gene responding to common carp PUFA contents and that fads.751 might be the main effect SNP. These cSNPs would be potential markers for future selection to improve the PUFA contents in common carp. [ABSTRACT FROM AUTHOR]

Pandalus borealis is an important indicator species to study the state of the Arctic ecosystem. The mitochondrial genome of P. borealis is 15,956 bp in length and encodes 13 protein-coding genes. The phylogenetic tree of eleven shrimps revealed that P. borealis belonged to Pandalidae family and was closely related to C. crassicornis. This mitogenome will be of significance to study the Arctic ecosystem state and perform the resource protection of this species. [ABSTRACT FROM AUTHOR]

Schizothorax taliensis is a national key protected fish in China. The mitochondrial genome of S. taliensis is 16,578 bp in length and includes two ribosomal RNA genes, 22 tRNA genes, and 13 protein-coding genes. The phylogenetic analysis showed that S. taliensis belongs to Cyprinidae family and is closely related to other Schizothorax fish. This mitogenome will contribute to the further conservation and genetic studies of this endangered fish. [ABSTRACT FROM AUTHOR]

Recent translational studies highlighted the inhibition of transforming growth factor (TGF)-β signaling as a promising target to treat pulmonary arterial hypertension (PAH). However, it remains unclear whether alterations in TGF-β signaling are consistent between PAH patients and animal models. Therefore, we compared TGF-β signaling in the lungs of PAH patients and rats with experimental PAH induced by monocrotaline (MCT) or SU5416+hypoxia (SuHx). In hereditary PAH (hPAH) patients, there was a moderate increase in both TGFβR2 and pSMAD2/3 protein levels, while these were unaltered in idiopathic PAH (iPAH) patients. Protein levels of TGFβR2 and pSMAD2/3 were locally increased in the pulmonary vasculature of PAH rats under both experimental conditions. Conversely, the protein levels of TGFβR2 and pSMAD2/3 were reduced in SuHx while slightly increased in MCT. mRNA levels of plasminogen activator inhibitor (PAI)-1 were increased only in MCT animals and such an increase was not observed in SuHx rats or in iPAH and hPAH patients. In conclusion, our data demonstrate considerable discrepancies in TGFβ-SMAD signaling between iPAH and hPAH patients, as well as between patients and rats with experimental PAH. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by obstructed pulmonary vasculatures. Current therapies for PAH are limited and only alleviate symptoms. Reduced levels of BMPR2 are associated with PAH pathophysiology. Moreover, reactive oxygen species, inflammation and autophagy have been shown to be hallmarks in PAH. We previously demonstrated that MnTBAP, a synthetic metalloporphyrin with antioxidant and anti-inflammatory activity, inhibits the turn-over of BMPR2 in human umbilical vein endothelial cells. Therefore, we hypothesized that MnTBAP might be used to treat PAH. Human pulmonary artery endothelial cells (PAECs), as well as pulmonary microvascular endothelial (MVECs) and smooth muscle cells (MVSMCs) from PAH patients, were treated with MnTBAP. In vivo, either saline or MnTBAP was given to PAH rats induced by Sugen 5416 and hypoxia (SuHx). On PAECs, MnTBAP was found to increase BMPR2 protein levels by blocking autophagy. Moreover, MnTBAP increased BMPR2 levels in pulmonary MVECs and MVSMCs isolated from PAH patients. In SuHx rats, MnTBAP reduced right ventricular (RV) afterload by reversing pulmonary vascular remodeling, including both intima and media layers. Furthermore, MnTBAP improved RV function and reversed RV dilation in SuHx rats. Taken together, these data highlight the importance of MnTBAP as a potential therapeutic treatment for PAH. [ABSTRACT FROM AUTHOR]

Background: Mutations in bone morphogenetic protein receptor type II (BMPR2) are leading to the development of hereditary pulmonary arterial hypertension (PAH). In non-hereditary forms of PAH, perturbations in the transforming growth factor-β (TGF-β)/BMP-axis are believed to cause deficient BMPR2 signaling by changes in receptor expression, the activity of the receptor and/or downstream signaling. To date, BMPR2 expression and its activity in the lungs of patients with non-hereditary PAH is poorly characterized. In recent decades, different animal models have been used to understand the role of BMPR2 signaling in PAH pathophysiology. Specifically, the monocrotaline (MCT) and Sugen–Hypoxia (SuHx) models are extensively used in interventional studies to examine if restoring BMPR2 signaling results in PAH disease reversal. While PAH is assumed to develop in patients over months or years, pulmonary hypertension in experimental animal models develops in days or weeks. It is therefore likely that modifications in BMP and TGF-β signaling in these models do not fully recapitulate those in patients. In order to determine the translational potential of the MCT and SuHx models, we analyzed the BMPR2 expression and activity in the lungs of rats with experimentally induced PAH and compared this to the BMPR2 expression and activity in the lungs of PAH patients. Methods: the BMPR2 expression was analyzed by Western blot analysis and immunofluorescence (IF) microscopy to determine the quantity and localization of the receptor in the lung tissue from normal control subjects and patients with hereditary or idiopathic PAH, as well as in the lungs of control rats and rats with MCT or SuHx-induced PAH. The activation of the BMP pathway was analyzed by determining the level and localization of phosphorylated Smad1/5/8 (pSmad 1/5/8), a downstream mediator of canonical BMPR2 signaling. Results: While BMPR2 and pSmad 1/5/8 expression levels were unaltered in whole lung lysates/homogenates from patients with hereditary and idiopathic PAH, IF analysis showed that BMPR2 and pSmad 1/5/8 levels were markedly decreased in the pulmonary vessels of both PAH patient groups. Whole lung BMPR2 expression was variable in the two PAH rat models, while in both experimental models the expression of BMPR2 in the lung vasculature was increased. However, in the human PAH lungs, the expression of pSmad 1/5/8 was downregulated in the lung vasculature of both experimental models. Conclusion: BMPR2 receptor expression and downstream signaling is reduced in the lung vasculature of patients with idiopathic and hereditary PAH, which cannot be appreciated when using human whole lung lysates. Despite increased BMPR2 expression in the lung vasculature, the MCT and SuHx rat models did develop PAH and impaired downstream BMPR2-Smad signaling similar to our findings in the human lung. [ABSTRACT FROM AUTHOR]

Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research. [ABSTRACT FROM AUTHOR]

1,5,9-Tribromo-2,3,6,7,10,11-hexamethoxy-4b 1 -methyltribenzotriquinacene, a C 3 -symmetric TBTQ derivative, can be prepared conveniently and with high regioselectivity from readily available starting materials. It is a versatile key compound for the synthesis of other chiral 1,5,9-trifunctionalized TBTQ derivatives and π-extended congeners in which the bays of the TBTQ skeleton are bridged by vinylene and 1,2-arylene units. X-ray crystal structure analysis and UV-vis spectroscopy show that vinylene bay-bridging enables better π-conjugation with the arene rings of the TBTQ core than 1,2-arylene bay-bridging does., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC)., Methods: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI., Results: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P<0.05). Multivariate analyses revealed that high GNRI is an independent prognostic factor for OS and PFS (hazard ratio, HR, 0.471, 95% CI, 0.270-0.822, P=0.008; HR 0.638, 95% CI, 0.433-0.941, P=0.023, respectively). Using a combination of baseline GNRI and EBV DNA, a satisfying separation of survival curves between different risk groups for OS, PFS, DMFS was observed. The survival rates of patients in the high-risk group were significantly lower than those in the low- and medium-risk groups (all P<0.001). The combined classification was demonstrated to be an independent prognostic factor for OS and PFS after adjustment using multivariate analysis., Conclusions: Pretreatment GNRI is an independent prognostic factor for NPC patients. The combination of baseline GNRI score and EBV DNA level improved the prognostic stratification of NPC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6493). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)