Explore the vast range of titles available.

Darwin’s naturalization conundrum describes two seemingly contradictory hypotheses regarding whether alien species closely or distantly related to native species should be more likely to naturalize in regional floras. Both expectations have accumulated empirical support, and whether such apparent inconsistency can be reconciled at the global scale is unclear. Here, using 219,520 native and 9,531 naturalized alien plant species across 487 globally distributed regions, we found a latitudinal gradient in Darwin’s naturalization conundrum. Naturalized alien plant species are more closely related to native species at higher latitudes than they are at lower latitudes, indicating a greater influence of preadaptation in harsher climates. Human landscape modification resulted in even steeper latitudinal clines by selecting aliens distantly related to natives in warmer and drier regions. Our results demonstrate that joint consideration of climatic and anthropogenic conditions is critical to reconciling Darwin’s naturalization conundrum. Alien species could be either more or less likely to become naturalized where closely related species occur. This study reveals a global latitudinal pattern whereby successfully naturalized alien plants are more closely related to natives at higher latitudes, reinforced by human modification of the environment.

A central question in ecology is why alien species naturalize successfully in some regions but not in others. While some hypotheses suggest aliens are more likely to naturalize in environments similar to donor regions, others suggest they thrive in regions where certain characteristics are different. Using the native (i.e., donor) and recipient distributions of 11,604 naturalized alien plant species across 650 regions globally, we assess whether plants are more likely to naturalize in regions that are ecologically similar or dissimilar to their donor regions. Our results show that species are more likely to naturalize in recipient regions where climates are similar and native floras are phylogenetically similar to those of their donor regions, indicating that pre-adaptation to familiar biotic and abiotic conditions facilitates naturalization. However, naturalization is also more likely in regions with lower native flora diversity and more intense human modification than in the species’ native range. Among all predictors, climate similarity and difference in native flora diversity emerge as the strongest predictors of naturalization success. In conclusion, ecological similarity in some factors but dissimilarity in others between donor and recipient regions promote the naturalization of alien plants and contribute to their uneven global distribution patterns. Across a global dataset of over 11,000 naturalized alien plant species, the authors find that species are likely to naturalize both in regions with climates and floras similar to those in their native ranges, and in regions with a lower diversity or stronger human impact than in their native range.

We aimed to evaluate the incidence of organ cysts in patients with type A aortic dissection (TAAD) to assess the association between organ cysts and TAAD. Between January 2018 and December 2018, all patients with TAAD undergoing aortic surgery at our center were enrolled into the study; patients undergoing isolated coronary artery bypass grafting at our center were selected as the control group. Baseline differences between the 2 groups were adjusted using propensity-score matching. The incidence of organ cysts was compared between the 2 groups in total and matched cohorts. We enrolled 290 patients with TAAD and 293 patients with coronary artery disease (control group). The incidence of all organ cysts, liver cysts, renal cysts, and other organ cysts, was significantly higher in the TAAD group than in the control group (50.0% vs. 35.5%, p<0.001; 24.5% vs. 10.2%, p<0.001; 33.4% vs. 24.9%, p=0.023; and 6.2% vs. 1.5%, p=0.005; respectively). Among the 191 propensity score-matched patient pairs, the incidence of organ cysts, liver cysts, renal cysts, and other organ cysts was also significantly higher in the TAAD group than in the control group (57.6% vs. 30.9%, p<0.001; 28.8% vs. 11.0%, p<0.001; 39.3% vs. 19.9%, p<0.001; and 8.4% vs. 1.0%, p=0.001; respectively). The incidence of cysts with single-organ and multiple-organ involvement was also significantly higher in the TAAD group than in the control group (34.0% vs. 20.4%, p=0.003; and 23.6% vs. 10.5%, p=0.001). Our results show a higher incidence of organ cysts in patients with TAAD which is indicative of a common pathogenetic pathway between organ cysts and aortic dissection.

Tomato yellow ring virus (TYRV), first isolated from tomato in Iran, was classified as a non-approved species of the genus Tospovirus based on the characterization of its genomic S RNA. In the current study, the complete sequences of the genomic L and M RNAs of TYRV were determined and analyzed. The L RNA has 8,877 nucleotides (nt) and codes in the viral complementary (vc) strand for the putative RNA-dependent RNA polymerase (RdRp) of 2,873 amino acids (aa) (331 kDa). The RdRp of TYRV shares the highest aa sequence identity (88.7 %) with that of Iris yellow spot virus (IYSV), and contains conserved motifs shared with those of the animal-infecting bunyaviruses. The M RNA contains 4,786 nt and codes in ambisense arrangement for the NSm protein of 308 aa (34.5 kDa) in viral sense, and the Gn/Gc glycoprotein precursor (GP) of 1,310 aa (128 kDa) in vc-sense. Phylogenetic analyses indicated that TYRV is closely clustered with IYSV and Polygonum ringspot virus (PolRSV). The NSm and GP of TYRV share the highest aa sequence identity with those of IYSV and PolRSV (89.9 and 80.2–86.5 %, respectively). Moreover, the GPs of TYRV, IYSV, and PolRSV share highly similar characteristics, among which an identical deduced N-terminal protease cleavage site that is distinct from all tospoviral GPs analyzed thus far. Taken together, the elucidation of the complete genome sequence and biological features of TYRV support a close ancestral relationship with IYSV and PolRSV.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

Xeroderma pigmentosum, complementation group C (XPC) is an accessory recognition gene involved in the nucleotide excision repair (NER) pathway, which is activated during the initial DNA damage recognition stage. It participates in the regulation of DNA damage-induced proliferation and apoptosis. Emerging evidence demonstrates that upregulation of XPC increases the resistance of several tumor cell types to cytotoxic drugs. In addition, it can predict poor patient outcome for non-small cell lung cancer (NSCLC). However, the mechanisms linking upregulation of XPC and drug resistance in lung cancer are still unclear. In the present study, we aimed to confirm whether XPC was involved in the reversal of the cisplatin (DDP) resistance in drug-resistant A549/DDP lung adenocarcinoma cells. RT-PCR and western blot assays were used to examine XPC mRNA and protein expression levels. Cell viability was assessed by CCK-8 assay. The knockdown of XPC was achieved in A549/DDP cells using si-RNA, whereas cell proliferation and apoptosis were assessed by wound healing assay and flow cytometric analysis, respectively. The median inhibitory concentration (IC50) value of DDP was assessed by CCK-8 assay. Western blot assays were conducted for the examination of caspase-9/3, Bax and Bcl-2 protein levels, whereas the activation of the PI3K/Akt/mTOR signaling pathway was investigated in XPC-knockdown cells. High expression of XPC was noted in A549/DDP cells compared with that in A549 cells, which was associated with DDP resistance. XPC silencing significantly inhibited A549/DDP cell proliferation and increased the induction of apoptosis. In addition, XPC knockdown decreased the expression levels of the Akt/mTOR signaling proteins and the expression of their downstream mediator. The data of the present study revealed that XPC inhibition rescued DDP resistance in lung adenocarcinoma cells, which was dependent on the Akt/mTOR signaling pathway. Collectively, XPC may be considered a new strategy for curing DDP-resistant lung cancer and may improve the efficacy of conventional chemotherapy.

The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1-147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1-147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex.

Ionizing radiation-induced intestinal injury is a catastrophic complication in patients receiving radiotherapy. Circulating exosomes from patients undergoing radiotherapy can mediate communication between cells and facilitate a variety of pathological processes in vivo, but its effects on ionizing radiation-induced intestinal damage are undetermined. In this study we investigated the roles of exosomes during total body irradiation (TBI)-induced intestinal injury in vivo and in vitro. We isolated exosomes from serum of donor mice 24 h after lethal dose (9 Gy) TBI (Exo-IR-24h), then intravenously injected the exosomes into receipt mice, and found that Exo-IR-24h injection not only exacerbated 9 Gy TBI-induced lethality and weight loss, but also promoted crypt-villus structural and functional injury of the small intestine in receipt mice. Moreover, Exo-IR-24h injection significantly enhanced the apoptosis and DNA damage of small intestine in receipt mice following TBI exposure. In murine intestinal epithelial MODE-K cells, treatment with Exo-IR-24h significantly promoted 4 Gy ionizing radiation-induced apoptosis, resulting in decreased cell vitality. We further demonstrated that Exo-IR-24h promoted the IR-induced injury in receipt mice partially through its DNA damage-promoting effects and attenuating Nrf2 antioxidant response in irradiated MODE-K cells. In addition, TBI-related miRNAs and their targets in the exosomes of mice were enriched functionally using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, injection of GW4869 (an inhibitor of exosome biogenesis and release, 1.25 mg·kg −1 ·d −1 , ip, for 5 consecutive days starting 3 days before radiation exposure) was able to rescue mice against 9 Gy TBI-induced lethality and intestinal damage. Collectively, this study reveals that exosomes are involved in TBI-induced intestinal injury in mice and provides a new target to protect patients against irradiation-induced intestinal injury during radiotherapy.

Nicotine is proved to be an important factor for cardiac hypertrophy. Autophagy is important cell recycling system involved in the regulation of cardiac hypertrophy. Cilostazol, which is often used in the management of peripheral vascular disease. However, the effects of cilostazol on nicotine induced autophagy and cardiac hypertrophy are unclear. Here, we aim to determine the role and molecular mechanism of cilostazol in alleviating nicotine-induced cardiomyocytes hypertrophy through modulating autophagy and the underlying mechanisms. Our results clarified that nicotine stimulation caused cardiomyocytes hypertrophy and autophagy flux impairment significantly in neonatal rat ventricular myocytes (NRVMs), which were evidenced by augments of LC3-II and p62 levels, and impaired autophagosomes clearance. Interestingly, cathepsin B (CTSB) activity decreased dramatically after stimulation with nicotine in NRVMs, which was crucial for substrate degradation in the late stage of autophagy process, and cilostazol could reverse this effect dramatically. Intracellular ROS levels were increased significantly after nicotine exposure. Meanwhile, p38MAPK and JNK were activated after nicotine treatment. By using ROS scavenger N-acetyl-cysteine (NAC) could reverse the effects of nicotine by down-regulation the phosphorylation of p38MAPK and JNK pathways, and pretreatment of specific inhibitors of p38MAPK and JNK could restore the autophagy impairment and cardiomyocytes hypertrophy induced by nicotine. Moreover, CTSB activity of lysosome regained after the treatment with cilostazol. Cilostazol also inhibited the ROS accumulation and the activation of p38MAPK and JNK, which providing novel connection between lysosome CTSB and ROS/p38MAPK/JNK related oxidative stress pathway. This is the first demonstration that cilostazol could alleviate nicotine induced cardiomyocytes hypertrophy through restoration of autophagy flux by activation of CTSB and inhibiting ROS/p38/JNK pathway, exhibiting a feedback loop on regulation of autophagy and cardiomyocytes hypertrophy.

Taraxacum mongolicum Hand.-Mazz (TMHM), a primary source of dandelion, is a globally recognized edible and medicinal plant with significant potential in food, medicine, daily chemical products, and animal husbandry. Although hypoglycemic effects have been reported in other Taraxacum species, the specific hypoglycemic constituents and mechanisms of TMHM are not well understood. The absence of comprehensive multi-target screening methodologies has hindered the elucidation of TMHM’s dual inhibitory effects on α-amylase and α-glucosidase, as well as its associated molecular mechanisms. In this study, a multi-target screening strategy was developed to concurrently evaluate α-amylase and α-glucosidase inhibition, integrating multi-target affinity ultrafiltration coupled with ultra-performance liquid chromatography-tandem mass spectrometry (MTAUF-UPLC-MS/MS), molecular docking, and molecular dynamics (MD) simulations. Using this approach, 13 dual-target inhibitors were identified from TMHM. Moreover, at least 5 of these compounds exhibited anti-diabetic activities comparable to the positive control drug acarbose, suggesting that they are principal bioactive constituents responsible for its hypoglycemic effects. Subsequent investigation of the antioxidant capacities of 7 out of the 13 bioactive compounds revealed that most exhibited more potent antioxidant activities than vitamin C (Vc). Based on these findings, molecular docking and MD simulations further validated that quercetin (8) and kaempferol (15), which demonstrated significant hypoglycemic and antioxidant activities, exhibited particularly strong affinities and stable interactions with α-amylase and α-glucosidase, respectively. In conclusion, these findings underscored the considerable potential of TMHM as a natural source of multifunctional bioactive compounds for nutraceutical, functional, and pharmaceutical applications. This study provided a critical foundation for elucidating the mechanisms underlying TMHM’s anti-diabetic effects and its therapeutic potential in mitigating diabetes-related complications, thereby facilitating future development and utilization.