Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.

A retrospective study on the relationship between serum electrolyte disorder and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.

Upregulated Cytoskeletal Proteins Promote Pathological Angiogenesis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare progressive vascular disease that leads to intracranial internal carotid artery stenosis and eventual occlusion. However, its pathogenesis remains unclear. The purpose of this study is to explore the role of abnormally expressed proteins in the pathogenesis of MMD. METHODS: Data-independent acquisition mass spectrometry identifies the differentially expressed proteins in MMD serum by detecting the serum from 60 patients with MMD and 20 health controls. The differentially expressed proteins were validated using enzyme linked immunosorbent assays. Immunofluorescence for superficial temporal artery and middle cerebral artery specimens was used to explore the morphological changes of vascular wall in MMD. In vitro experiments were used to explore the changes and mechanisms of differentially expressed proteins on endothelial cells. RESULTS: Proteomic analysis showed that a total of 14 726 peptides and 1555 proteins were quantified by mass spectrometry data. FLNA (filamin A) and ZYX (zyxin) proteins were significantly higher in MMD serum compared with those in health controls (Log2FC >2.9 and >2.8, respectively). Immunofluorescence revealed an intimal hyperplasia in superficial temporal artery and middle cerebral artery specimens of MMD. FLNA and ZYX proteins increased the proportion of endothelial cells in S phase and promoted their proliferation, angiogenesis, and cytoskeleton enlargement. Mechanistic studies revealed that AKT (serine/threonine kinase)/GSK-3ß (glycogen synthase kinase 3ß)/ß-catenin signaling pathway plays a major role in these FLNA- and ZYX-induced changes in endothelial cells. CONCLUSIONS: This study provides proteomic data on a large sample size of MMD. The differential expression of FLNA and ZYX in patient with MMD and following in vitro experiments suggest that these upregulated proteins are related to the pathology of cerebrovascular intimal hyperplasia in MMD and are involved in MMD pathogenesis, with diagnostic and therapeutic ramifications.

Prevalence and Procedural Risk of Intracranial Atherosclerotic Stenosis Coexisting With Unruptured Intracranial Aneurysm.

BACKGROUND: Coexistence of intracranial atherosclerotic stenosis (ICAS) and unruptured intracranial aneurysms (UIAs) is increasingly encountered in clinical practice. This study aims to determine the prevalence of ICAS in patients with UIAs and procedural ischemic risk associated with ICAS when treating UIAs. METHODS: Based on the CAIASA study (Coexistence of Atherosclerotic Intracranial Arterial Stenosis With Intracranial Aneurysms), we prospectively included patients undergoing treatment procedures for UIAs from October 2015 to December 2020 at Beijing Tiantan Hospital, China. We used computed tomography angiography or digital subtraction angiography to diagnose ICAS (stenosis≥50%). Multivariable logistic regression and propensity-score matching were performed to evaluate the risk of procedure-related ischemic stroke and unfavorable outcome associated with ICAS. The ICAS score was used to explore the association between different burden of ICAS and procedure-related ischemic risk. RESULTS: Among 3949 patients who underwent endovascular or open surgical procedures for UIAs, 245 (6.2%) had ICAS. After exclusion, 15.7% (32/204) of patients with ICAS experienced procedure-related ischemic stroke compared with 5.0% (141/2825) of patients without ICAS. From the unmatched and matched cohort, ICAS was significantly associated with increased risk of procedure-related ischemic stroke (unmatched: adjusted odds ratio=3.11 [1.89-5.11]; and matched: adjusted odds ratio=2.99 [1.38-6.48]). This association became more evident among patients not receiving antiplatelet therapy (Pinteraction=0.022). For patients undergoing different treatment modalities, similar increased risks were observed (clipping: adjusted odds ratio=3.43 [1.73-6.79]; and coiling: adjusted odds ratio=3.59 [1.94-6.65]). Higher ICAS score was correlated with higher procedural ischemic risk (Ptrend<0.001). CONCLUSIONS: The occurrence of ICAS is not infrequent in patients with UIAs. ICAS confers an ~2-fold increased procedural ischemic risk, irrespective of clipping or coiling. Previous antiplatelet therapy may decrease the risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795078.

Mycoplasma infection of cancer cells enhances anti-tumor effect of oxidized methylcytidines.

Oxidized methylcytidines 5-hydroxymethyl-2'deoxycytidine (5hmdC) and 5-formy-2'deoxycytidine (5fdC) are deaminated by cytidine deaminase (CDA) into genome-toxic variants of uridine, triggering DNA damage and cell death. These compounds are promising chemotherapeutic agents for cancer cells that are resistant to pyrimidine derivative drugs, such as decitabine and cytarabine, which are inactivated by CDA. In our study, we found that cancer cells infected with mycoplasma exhibited a markedly increased sensitivity to 5hmdC and 5fdC, which was independent of CDA expression of cancer cells. In vitro biochemical assay showed that the homologous CDA protein from mycoplasma was capable of deaminating 5hmdC and 5fdC into their uridine form. Moreover, mycoplasma infection increased the sensitivity of cancer cells to 5hmdC and 5fdC, whereas administration of Tetrahydrouridine (THU) attenuated this effect, suggesting that mycoplasma CDA confers a similar effect as human CDA. As mycoplasma infection occurs in many primary tumors, our findings suggest that intratumoral microbes could enhance the tumor-killing effect and expand the utility of oxidized methylcytidines in cancer treatment.

Age-related macrophage alterations are associated with carcinogenesis of colorectal cancer.

Older age is a major risk factor for colorectal cancer. Macrophage is one of the most abundant immune cell types infiltrated in colorectal cancer, but the contribution of macrophages in elder tumor microenvironment is far from clear. In this study, we first detected the expression of CD206, CD68 in colorectal cancer tissues by multiplex fluorescence immunohistochemical staining. The infiltration of CD68+/CD206+ cells in tumor tissues from old patients was higher than those from young patients. When mixed with CT26 cells, both young and aged TAMs enhanced tumor growth of CT26 cells, but CT26 mixed with aged TAMs form larger tumors compared with young TAMs. CT26 formed more and larger tumors in the abdominal cavity of aged mice compared with young. Total macrophage infiltration and the CD206+ macrophages infiltration were both higher in aged mice compared with young mice. The expression signatures of tumor-associated macrophages altered with ageing and p-NF-κB translocation to nucleus was more significant in TAMs from aged mice compared with young. Our results showed that infiltration of macrophages in colorectal cancer tissues increased with ageing. Macrophages from aged host were more likely to polarize to pro-tumor phenotype, and more powerful in promoting tumor cell proliferation.

Decision-free downsampling method assisted via channel-transfer information to improve the reliability of holographic data storage systems.

A decision-free downsampling method (DFDS) assisted by channel-transfer information for phase-modulated holographic data storage is proposed. DFDS is used to address the issue of the accumulation of decision errors induced by traditional downsampling. The issue degrades the downsampling accuracy. DFDS comprises two functional segments: acquiring the channel-transfer information offline and performing decision-free downsampling online. With the assistance of the channel-transfer information, DFDS uses Bayesian posterior probabilities instead of traditional decision results to avoid the accumulation of decision errors and achieve more accurate downsampling. The simulation and experimental results show that DFDS reduces the phase error rate, thereby improving the reliability of the holographic data storage system.

Improving the data reliability of phase modulated holographic storage using a reliable bit aware low-density parity-check code.

Phase modulated holographic storage offers superior storage capacity and a longer life span compared with other storage technologies. However, its application is limited by its high raw bit error rate. We aimed to introduce low-density parity-check (LDPC) codes for data protection in phase modulated holographic storage systems. However, traditional LDPC codes can not fully exploit data error characteristics, causing inaccurate initial log-likelihood ratio (LLR) information, which degrades decoding performance, thus limiting the improvement degree of data reliability in phase modulated holographic storage. Therefore, we propose a reliable bit aware LDPC optimization method (RaLDPC) that analyzes and employs phase demodulation characteristics to obtain reliable bits. More accurate initial LLR weights are assigned to these reliable bits. Hence, the optimized initial LLR can reflect the reliability of the demodulated data more accurately. Experimental results show that RaLDPC can reduce the bit error rate by an average of 38.89% compared with the traditional LDPC code, improving the data reliability of phase modulated holographic storage.

Phase-distribution-aware adaptive decision scheme to improve the reliability of holographic data storage.

Owing to their high storage density and long storage life, holographic data storage (HDS) technologies are viable options for mass cold data storage in the era of big data. Phase-modulated holographic data storage (PHDS) is a promising implementation of HDS. However, because of complex noise in the storage channel, many errors remain after phase demodulation. This study investigates the phase decision in the data-reading stage of PHDS. We propose a phase-distribution-aware adaptive (PDAA) decision scheme to address the inaccurate thresholds in traditional phase decision schemes. The PDAA decision scheme can determine more accurate decision thresholds based on the phase distribution characteristics of each reconstructed phase data page and adaptively match different decision thresholds to each phase data page. The experimental results show that when compared to the traditional decision scheme, the PDAA decision scheme can significantly reduce the phase error of data pages, improving the data reliability of holographic storage.

Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice.

BACKGROUND: Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. OBJECTIVES: This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. METHODS: Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test. RESULTS: The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1ß concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05). CONCLUSIONS: Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Improving reliability using phase distribution aware LDPC code for holographic data storage.

The iterative Fourier transform (IFT) algorithm is an effective solution for phase retrieval in phase-type holographic data storage systems, but introduces a higher phase error rate. As a result, data reliability becomes a significant issue. In this paper, to improve reliability and decrease decoding latency, we propose a phase distribution aware low-density parity-check (LDPC) code [called point data abstraction library (PDAL)] with outstanding error correcting capability. After experiencing IFT, we first investigate the phase distribution characteristics and find that the adjacent phase distribution is more likely to cross, resulting in higher phase shift percentages. Then, using phase distribution, PDAL optimizes LDPC codes with higher precision decoding information by dynamically applying the phase threshold based on the phase error rate. When the phase error rate is 0.04, the bit error rate, decoding iteration times, and decoding failure rate are all reduced by 51.5%, 26.9%, and 51.8% on average, respectively, compared with traditional LDPC code without exploiting phase distribution. PDAL, which is an efficient and practical error correction approach for phase-modulated holographic data storage, can improve data reliability by boosting error correction performance.

Elevated blood hemoglobin on admission as an independent predictor of unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage.

Hemoglobin (HGB), a potent spasmogen, may cause irreversible damage to the brain after aneurysm rupture. However, there is no clinical evidence to reveal the relationship between blood HGB concentrations on admission and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to our institution between January 2015 and December 2020. Functional outcome was assessed at 90 days after discharge using the modified Rankin scale (mRS). Independent risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cutoff value of HGB to discriminate 90-day unfavorable outcomes. Then, patients were divided into two groups according to the cutoff value of HGB, and to account for imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of HGB on in-hospital complications. A total of 800 aSAH patients without anemia on admission were retrospectively enrolled in this study. Elevated blood HGB (OR = 1.02, 95% CI = 1.00-1.03, p = 0.018) on admission was identified as an independent risk factor associated with 90-day unfavorable outcomes, and the cutoff value was 149.5 g/L. After PSM, patients with an HGB > 149.5 g/L had a higher incidence of in-hospital delayed cerebral ischemia (DCI) (33.9% vs. 22.0%, p = 0.013) and deep vein thrombosis (DVT) (11.9% vs. 4.0%, p = 0.006). Patients with a blood HGB > 149.5 g/L on admission might develop more DCI and DVT during hospitalization, leading to 90-day unfavorable outcomes in aSAH patients. ClinicalTrials.gov Identifier: NCT04785976. 2021/03/05, retrospectively registered.

The effect of sex differences on complications and 90-day outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered.

Transcranial color Doppler sonography as an alternative tool for evaluation of terminal internal carotid artery steno-occlusion in moyamoya disease.

OBJECTIVE: To investigate color Doppler ultrasonography criteria and its value in assessing the steno-occlusion of the terminal internal carotid artery in moyamoya disease. METHODS: According to the digital subtraction angiography findings, patients were divided into three groups: occlusion of the terminal internal carotid artery, >50% stenosis, and ≤50% stenosis. We measured the terminal and proximal internal carotid artery parameters of each group using transcranial and cervical color Doppler sonography. RESULTS: Blood flow signals in 12 terminal internal carotid arteries were absent, which were verified as occlusion by digital subtraction angiography. Parameters were obtained in the remaining 159 terminal/proximal internal carotid arteries to predict cutoffs for >50% stenosis and occlusion. For >50% stenosis, mean flow velocity >88.50 cm/s in the terminal internal carotid artery could achieved the highest receiver operating characteristic curve area of 0.776 with 62.50% sensitivity, 88.15% specificity, 48.39% positive predictive values, 92.97% negative predictive value, and 84.27% overall accuracy. For the occlusion, mean flow velocity <49.50 cm/s in the terminal internal carotid artery achieve the highest receiver operating characteristic curve area of 0.734 with 55.56% sensitivity, 83.81% specificity, 63.83% positive predictive values, 78.57% negative predictive value, and 74.21% overall accuracy. The area under receiver operating characteristic curve cutoffs for other parameters were less than 0.7. CONCLUSION: Mean flow velocity of terminal internal carotid artery provides useful diagnostic information for detecting steno-occlusion in moyamoya disease. It may be used as an alternative tool to evaluate steno-occlusion of the terminal internal carotid artery in moyamoya disease.

Clinical Implications of the "Brush Sign" in Susceptibility-Weighted Imaging for Moyamoya Disease.

OBJECTIVE: Infarction is one of the most common postoperative complications after surgical revascularization for moyamoya disease (MMD). Increased conspicuity of deep medullary veins (DMVs) on susceptibility-weighted imaging (SWI), known as "brush sign," could predict the severity of MMD. This study aimed to reveal the features of the "brush sign" in preoperative SWI and to verify its relationship to postoperative infarction. METHODS: Consecutive patients with MMD who had undergone cerebral revascularization surgery were included. Routine preoperative SWI was performed. The "brush sign" was defined according to the number of the conspicuous DMVs > 5 detected on SWI. Postoperative infarctions were defined as the high-intensity signal on postoperative DWI images, with or without neurologic deficits. The modified Rankin scale (mRS) was applied to evaluate the prognosis of patients. RESULTS: In the enrolled 100 hemispheres, 35 were presented with the "brush sign." Patients with ischemic onset manifestation and previous infarction history tended to present with the "brush sign." Multivariate analysis showed that the "brush sign" (OR 13.669; 95% CI, 1.747-106.967, p = 0.013) and decreased rCBF (OR 6.050; 95% CI, 1.052-34.799, p = 0.044) were independent risk factors of postoperative infarction. Besides, the "brush sign" showed a significant correlation with a higher mRS score at discharge (p = 0.047). CONCLUSION: The findings strongly suggest that the presence of the "brush sign" preoperatively can be a predictor of infarction after surgical revascularization for ischemic MMD. It may contribute to an improved surgical result through focused perioperative management based on appropriate surgical risk stratification.

Taxonomic revision and redescription of Microphysogobio hsinglungshanensis, the type species of Microphysogobio Mori, 1934 (Cypriniformes: Cyprinidae).

The genus Microphysogobio was established by Mori [Mori, T. (1934). The fresh water fishes of Jehol. In Report of the first scientific expedition to Manchoukuo. 1: pp. 1-61] based on a single specimen (Microphysogobio hsinglungshanensis) collected in the Luanhe River basin, Xinglong County, Hebei Province, China. Because the genus characteristics were derived from its type species, M. hsinglungshanensis, the detailed description is essential. In addition, to distinguish M. hsinglungshanensis and Microphysogobio chinssuensis, the description based on holotype and more specimens is needed. M. hsinglungshanensis can be distinguished from all other congeners by the following combination of characters: mouth shallow arc shaped and inferior; medial pad on lower lip inverted trapezoid and usually grooved; barbel short, 6.9%-14.3% in head length; lateral-line scales 38-39; ventral region between pectoral-fin origin and pelvic-fin origin scaleless; scales above lateral line 4-4.5; predorsal scales 10-11; vertebrae 4 + 32 - 34; caudal-fin membrane with two or three rows of irregular black spots. The characteristics of this genus were redefined based on M. hsinglungshanensis in this study.

High variance of intraoperative blood pressure predicts early cerebral infarction after revascularization surgery in patients with Moyamoya disease.

Few studies focused on the intraoperative blood pressure in Moyamoya disease (MMD) patients. We aimed to clarify whether or not it relates to early cerebral infarction after revascularization. We reviewed a retrospective cohort of Moyamoya disease from 2011 to 2018 in Beijing Tiantan Hospital, and patients with radiologically confirmed early postoperative infarction were included in the analysis. Controls were matched based on age, sex, and revascularization modality at a ratio of 1:5. Perioperative clinical factors and intraoperative blood pressure data were collected and analyzed. A total of 52 patients out of 1497 revascularization surgeries (3.5%) who experienced CT or MRI confirmed early postoperatively cerebral infarction, aged 38.46 ± 11.70; 26 were male (50.0%). Average real variability (ARV)-systolic blood pressure (SBP) (OR 3.29, p = 0.003), ARV-diastolic blood pressure (DBP) (OR 4.10, p = 0.005), ARV-mean arterial pressure (MAP) (OR 4.08, p = 0.004), and the maximum drops of DBP (OR 1.08, p = 0.003) and MAP (OR 1.06, p = 0.004) were associated with early postoperative infarction. In patients who experienced massive cerebral infarction, the maximum drops of DBP (OR 1.11, p = 0.004) and MAP (OR 1.11, p = 0.003) are independent risk factors, whereas ARVs of SBP (OR 3.90, p < 0.001), DBP (OR 4.69, p = 0.008), and MAP (OR 4.72, p = 0.003) are significantly associated with regional infarction. High variance of intraoperative blood pressure and drastic blood pressure decline are independent risk factors for postoperative infarction in MMD patients who underwent revascularization surgery. Maintaining stable intraoperative blood pressure is suggested to prevent early postoperative cerebral infarction in MMD patients.

UPLC-ESI-Q-TOF-MS/MS analysis of anticancer fractions from Ophiocordyceps xuefengensis and Ophiocordyceps sinensis.

Ophiocordyceps xuefengensis (O. xuefengensis), a new species of caterpillar fungus, has been identified as the sister taxon of Ophiocordyceps sinensis (O. sinensis). The aims of the present study are to evaluate the anticancer activity and to qualitatively analyze the potential bioactive chemical constituents of O. xuefengensis and O. sinensis, comparatively. An MTT assay was used to evaluate the in vitro anticancer activities of different fractions from O. xuefengensis and O. sinensis. The results show that ethyl acetate fractions of O. xuefengensis and O. sinensis have significant in vitro anticancer activity. These two bioactive fractions were analyzed by ultra-performance liquid chromatography-electrospray ionization with quadrupole-time of flight tandem mass spectrometry technology. A total of 82 compounds and 101 compounds were identified or tentatively characterized in the bioactive fractions of O. xuefengensis and O. sinensis, respectively. Among these compounds, 68 existed in both O. xuefengensis and O. sinensis. A total of 67 compounds were reported in O. xuefengensis and 8 compounds were reported in caterpillar fungus for the first time. This is the first detailed comparative analysis of the in vitro anticancer activity and chemical ingredients between O. xuefengensis and O. sinensis. The application of this work will provide reliable fundamental pharmacological substances for the use of O. xuefengensis by Yao people.

Oreonectes guilinensis (Teleostei, Cypriniformes, Nemacheilidae), a new loach species from Guangxi, China.

A new loach Oreonectes guilinensis sp. nov. is described from Guangxi Zhuang Autonomous Region, China. It is the second surface-dwelling fish identified in the genus Oreonectes after the type species Oreonectes platycephalus. This new species can be distinguished from other species within the genus by the combination of the following features: a round caudal fin, 13-14 branched rays, an incomplete lateral line with 4-6 pores, a short pelvic fin located some distance from the anus, a scale-covered body, a stout build (body width 14.0%-16.7% of standard length), a posterior chamber of well-developed airbladder and a yellowish-brown body with a lateral dark brown strip. The maximum likelihood phylogenetic analysis based on cytb gene recovered this new species in a well-supported clade with the type species O. platycephalus, sister to the Lefua clade. Morphological comparisons as well as our phylogenetic tree support Oreonectes shuilongensis, Oreonectes daqikongensis, Oreonectes jiarongensis as species of Troglonectes. Based on our results there are 6 valid species in the genus Oreonectes.

Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner.

Due to the increasing incidence and mortality, the early diagnosis, specific targeted therapies, and prognosis for colorectal cancer (CRC) attract more and more attention. Wild-type p53-induced phosphatase 1 (Wip1) and karyopherin α2 (KPNA2) have been regarded as oncogenes in many cancers, including CRC. Wip1 dephosphorylates p53 to inactivate it. TP53 activator and Wip1 inhibitor downregulate KPNA2 expression. Therefore, we speculate that Wip1 may co-operate with KPNA2 to modulate CRC progression in a p53-dependent manner. Here, Wip1 and KPNA2 messenger RNA expression and protein levels are significantly increased in CRC tissues and cell lines and are positively correlated with each other. Wip1 silence increases p53 phosphorylation while decreases KPNA2 protein. Wip1 knockdown remarkably suppresses CRC cell proliferation and migration while KPNA2 overexpression exerts an opposing effect. KPNA2 overexpression could partially rescue Wip1 silence-inhibited CRC cell proliferation and migration. Finally, Wip1 interacts with KPNA2 to modulate the activation of AKT/GSK-3ß signaling and metastasis-related factors. In summary, Wip1 could co-operate with KPNA2 to modulate CRC cell proliferation and migration, possibly via a p53-dependent manner, through downstream AKT/GSK-3ß pathway. We provided a novel mechanism of Wip1 interacting with KPNA2, therefore modulating CRC cell proliferation and migration.