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Hui Wu,1– 3 Gui Zhen Weng,1 Li Na Sun,2 Zhang Chi Pan,1 Lu Zhang,4 Qiang Chen,1,3 Chun Mei Shi1,3 1Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 2Department of Oncology, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, 323000, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, 350001, People’s Republic of China; 4Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Chun Mei Shi, Email shichunmei@tom.comPurpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1-based immunotherapy in NSCLC is unknown.Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognoses were followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Survival curves were estimated by the Kaplan-Meier method, Cox regression analysis was used to identify factors associated with prognoses of NSCLC patients.Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P < 0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging may be associated with survival. Patients with higher Ki-67 expression on PD-1+CD8+ T-cells (pretreatment) had statistically significant increased progression-free survival (PFS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and overall survival (P < 0.05).Conclusion: Activation of circulating Tex cells before or during therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.Keywords: non-small cell lung cancer, immunotherapy, T cell invigoration, prognosis

Scorpions are an ancient and charismatic group of arthropods with medical importance, but a high-quality reference genome for this group is still lacking. Here we perform whole-genome sequencing of Mesobuthus przewalskii, a desert scorpion endemic to the Taklimakan Desert. We combine PacBio HiFi sequencing and Hi-C chromosome conformation capturing to generate chromosomal-level, haplotype-resolved, and fully annotated genome assembly for this medically important scorpion. The assembly consists of two haplotypes (1052.01 Mbp and 1055.19 Mbp, respectively) reaching chromosome-level contiguity and >98% BUSCO completeness. Sequences were anchored in 13 chromosomes with a contig N50 of 34.44 Mbp and scaffold N50 of 81.43 Mbp. Several key genome features and the mitochondrial genome assembly were also provided. This genome represents the fifth but the most complete assembly for the order Scorpiones., (© The Author(s) 2024. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Currently reported circularly polarized luminescent devices are primarily based on rare earth and noble metal complexes or lead perovskite materials. Reports on electroluminescent devices employing eco-friendly luminescent materials are notably scarce. In this study, we strategically designed and synthesized manganese complexes featuring Binapo as the chiral ligand. The complex structure reveals a tetrahedral coordination configuration, with the R / S configurations exhibiting a mirror relationship. Leveraging the strong ligand field and chiral structural characteristics of Binapo, the enantiomers display red emission and exhibit significant circularly polarized luminescence with a circularly polarized luminescence asymmetric factor ( g lum ) of 5.1 × 10 -3 . The circularly polarized electroluminescent performance was investigated by using a solution processing method and host-guest doping strategy. Our efforts resulted in device performance with an external quantum efficiency (EQE) exceeding 4%, and its electroluminescent asymmetric factor ( g EL ) reached an impressive -8.5 × 10 -3 . This surpasses the performance of most devices relying on platinum (Pt) and iridium (Ir) metal complexes and perovskite related materials. Our work establishes a pathway for the development of cost-effective and environmentally friendly chiral electroluminescent materials and devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: The Angoumois grain moth, Sitotroga cerealella, is a destructive pest of maize, wheat, and rice, causing economic losses and threatening food security. This study aimed to develop and characterize microcapsules of mesoporous silica nanospheres (MSN) and cyclodextrin-modified mesoporous silica nanospheres (CDMSN) containing two aldehydes, nonanal and decanal, found in plant essential oils, to assess their attractiveness to S. cerealella populations., Results: Microcapsules with 2:1 ratio of nonanal and decanal exhibited an average encapsulation efficiency of 39.82% for MSN loaded with nonanal and decanal (MSN-ND) and 46.10% for CDMSN loaded with nonanal and decanal (CDMSN-ND). They have an elliptical shape with particle sizes of 115 nm for MSN and 175 nm for CDMSN. Gas chromatography-mass spectrometry analysis revealed in vitro release of nonanal in MSN at 96.24% and decanal at 96.42% by the 36th day. CDMSN showed releases of 93.83% for nonanal and 93.74% for decanal by the 50th day. CDMSN-ND attracted adult S. cerealella for 43 days, while MSN-ND remained effective for 29 days. In mass trapping assays in simulated grain warehouse, both MSN-ND and CDMSN-ND trapped over 50% of the adult population within 7 days, significantly reducing grain infestation rates below 10% by inhibiting F1 adult emergence. At temperatures ranging from 20 °C to 35 °C, both microcapsules exhibited significant and effective attraction rates for S. cerealella. Stored wheat seeds treated with CDMSN and CDMSN-ND over 1 year showed no significant differences in key germination parameters., Conclusion: Microencapsulated nonanal and decanal offer a promising, sustainable approach for controlling S. cerealella infestation in stored grains, contributing to global food security. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rate of assisted reproductive technology (ART). Potential preventative strategies preventing oocytes from aging and the associated underlying mechanisms warrant investigation. In this study, we identified that cordycepin, a natural nucleoside analogue, promoted the quality of oocytes aging in vitro, as indicated by reduced oocyte fragmentation, improved spindle/chromosomes morphology and mitochondrial function, as well as increased embryonic developmental competence. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Strikingly, cordycepin was found to suppress the elevation of DCP1A protein by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during postovulatory aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin prevents postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via suppressing polyadenylation of DCP1A mRNA, thereby promoting oocyte developmental competence., (© 2023. The Author(s).)

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and β-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2020 Deng et al.)

Objective: To study the effect of propofol used for painless gastroscopy and colonoscopy on psychomotility recovery., Methods: One hundred adult patients undergoing painless gastroscopy and colonoscopy were recruited, aged 18-72 years, with American Society of Anesthesiologist (ASA) physical status Ⅰ-Ⅱ. According to age, the patients were divided into youth group (20-39 years old, 27 cases), middle age group (40-54 years old, 37 cases), and elder group (55-64 years old, 36 cases). Propofol was continuously infused according to the patients' condition to mantain the bispectal index (BIS) score 55-64. All the patients received psychomotility assesment 30 min before the operations when the discharge criteria were met including number cancellation test, number connection test and board test. The heart rate, blood pressure, saturation of pulse oximetry, electrocardiograph and BIS were monitored during the operation. The operating time, recovery time, total volume of propofol and discharge time were recorded. If the results obtained were inferior to those before operation, a third assessment was taken 30 minutes later until the results recovered or being superior to the baseline levels., Results: All the patients completed the first and second assessments, and 25 patients had taken the third assessment. There was no statistically significant difference in the results of psychomotility assessment when the patients met the discharge standard. Furthermore, the results were analyzed by grouping with age, and there was no statistical difference in the test results of the youth and middle age groups compared with the preoperative group, among which, the efficiency of the number cancellation test was significantly better than that before operation in the youth group ( P < 0.05). However, in the elderly patients the number cancellation efficiency, number connection test and board test were significantly inferior to that before operation ( P < 0.05). There was no significant difference in the accuracy of number cancellation compared with that before operation. The patients who needed the third test in the elder group were significantly more than in the other groups ( P < 0.05). Compared with the preoperative results, there was no statistical difference in the test results of those who completed the third test., Conclusion: The psychomotility function of the patients who underwent painless gastroscopy and colonoscopy was recovered when they met discharge criteria. The elderly patients had a prolonged recovery period.

Diallyl trisulfide (DAT) is a biologically active component of garlic essential oil and exhibits multi-targeted activity against many organisms. The current study tested the capacity of DAT to decrease the male fertility of Sitotroga cerealella . The effects on testis morphology, sperm number, motility, and lipid homeostasis were observed in adult males fumigated with DAT at a dose of 0.01 μL/L in air. The results indicated that the DAT significantly decreased the dimorphic sperm number. Meanwhile, the ultrastructural analysis of the sperm showed that the DAT caused malformed and aberrant structures of mitochondrial derivatives of dimorphic sperm. Additionally, the lipid homeostasis and ATP contents in the male adults were significantly decreased after treatment. Moreover, the total sperm motility was reduced, while the wave-propagation velocity, amplitude, frequency, and wavelength were significantly decreased compared with the controls. Overall, this study reported, for the first time, that DAT impairs energy metabolism, inhibits dimorphic spermatogenesis, and decreases sperm motility, while these abnormalities in sperm lead to adult-male infertility.

In recent years, the application of cell-based therapy in the field of refractory wound repair has shown broad prospects, among which the mesenchymal stem cell is the most concerned and widely studied cell type. Despite the rapid development of clinical translational research, the therapeutic effect of cell-based therapy is not consistent, and most clinical trials have not achieved the desired results. Further studies have found that heterogeneity is an important issue that restricts the further development of cell-based therapy and urgently needs to be studied. Based on the research progress of mesenchymal stem cells, in the review, we discuss the current status and challenges of cell-based therapy strategies for refractory wounds.

Objective: To investigate the effects of mitochondrion-targeted cyanine fluorescent small molecule IR-61 on cardiac injury induced by exhaustive exercise in rats., Methods: Thirty-six adult male SD rats were randomly divided into 3 groups( n =12),control group (Ctrl), exhaustive exercise group (EE) and IR-61+ exhaustive exercise group (IR-61+EE). IR-61+EE group were intraperitoneally injected with 2 mg/kg IR-61 at the same time on day 1, 4 and 7. One hour after the end of the last drug administration, the two exhaustive exercise groups were subjected to exhaustive exercise modeling. The rats were placed on an animal treadmill with a slope of 0° at a speed of 10~15 m/min to coordinate their limbs running posture, and then ran at a speed of 25~30 m/min until exhaustion about 15 minutes later. After the animal models established, ECG was recorded by physiological recorder, myocardial injury was observed by light microscope, mitochondrial injury was observed by transmission electron microscope, myocardial cell apoptosis was detected by TUNEL method, markers of myocardial injury were detected by ELISA, and myocardial mitochondrial respiration rate was measured by high-resolution Oxygraph-2K mitochondrial instrument., Results: ① Compared with Ctrl group, heart rate was increased, PR interval was shortened, QRS interval was prolonged, QTc was prolonged and ST segment was depressed significantly in EE group ( P ＜0.05). In EE group, myocardial fiber fracture and mitochondrial inner chamber swelling were obvious, mitochondrial crest was fuzzy, mitochondrial outer membrane was incomplete, and a large number of mitochondrial rupture and fusion were visible. In EE group, TUNEL staining cells were abundant, chromatin concentration and marginalization, nuclear membrane lysis, chromatin fragmentation into massive apoptotic bodies, apoptosis score increased ( P ＜0.05). The levels of creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I(cTn-I) and N-terminal B-type natriuretic peptide (NT-proBNP) were increased in EE group ( P ＜0.05). Basal respiration rate, oxidative respiration rate of fatty acids and respiration rate of complex Ⅰ, Ⅱ and Ⅳ were all decreased ( P ＜ 0.05). ② Compared with EE group, the heart rate in IR-61+EE group was increased, PR interval was prolonged, QRS interval was shortened, QTc was shortened, ST segment was not significantly depressed ( P ＜0.05). In IR-61+EE group, myocardial fiber arrangement was loose, no obvious fracture was observed, mitochondrial inner ventricle was swelling, mitochondrial outer membrane was intact, TUNEL stained cells and unstained cells were observed, the overall morphology was more similar to Ctrl group. Apoptosis index was decreased ( P ＜0.05), the levels of CK-MB and cTn-I were decreased in IR-61+EE group ( P ＜0.05). The oxidative respiration rate of fatty acids and the respiration rate of complex Ⅱ and Ⅳ were increased ( P ＜0.05)., Conclusion: Mitochondrion-targeted cyanine fluorescent small molecule IR-61 can improve cardiac electrical activity, reduce myocardial cell injury and mitochondrial injury, reduce myocardial cell apoptosis, and improve the myocardial mitochondrial energy metabolism condition in exhausted rats.

Circular polarized luminescence (CPL)-active materials attract great attentions owing to their widely applications in 3D optical displays and encrypted transmission. Inspired by the strategies adopted in perovskite based CPL materials, herein, CPL-active hybrids (D)- and (L)-(tert-butyl prolinate)MnCl 3 were successfully prepared by assembling chiral D/L tert-butyl prolinate with manganese (II) chloride. Single crystal structures show the as-formed hybrids possess one-dimensional (1D) structure containing linear chains of face-sharing MnCl 6 octahedral surrounded by prolinate cations. The 1D Mn(II) hybrids display strong red emission peaked at 646 nm with PLQY of 67.1 % and 57.2 % for d-type and l-type, respectively, representing the highest PLQY for 1D Mn II hybrids. Interestingly, the 1D Mn(II) hybrids exhibit prominent circular dichroism (CD) signals and remarkable CPL activity with the dissymmetry factor g of 6.1*10 -3 and -6.3*10 -3 from 550 to 800 nm for (D)- and (L)-(tert-butyl prolinate)MnCl 3 , respectively, owing to the existence of chiral cations. It is worthy noted the obtained g represents the highest value for non-lead organic-inorganic hybrids., (© 2022 Wiley-VCH GmbH.)

A comprehensive understanding of phylogeography requires the integration of knowledge across different organisms, ecosystems, and geographic regions. However, a critical knowledge gap exists in the arid biota of the vast Asian drylands. To narrow this gap, here we test an "out-of-Central Asia" hypothesis for the desert scorpion Mesobuthus mongolicus by combining Bayesian phylogeographic reconstruction and ecological niche modeling. Phylogenetic analyses of one mitochondrial and three nuclear loci and molecular dating revealed that M. mongolicus represents a coherent lineage that diverged from its most closely related lineage in Central Asia about 1.36 Ma and underwent radiation ever since. Bayesian phylogeographic reconstruction indicated that the ancestral population dispersed from Central Asia gradually eastward to the Gobi region via the Junggar Basin, suggesting that the Junggar Basin has severed as a corridor for Quaternary faunal exchange between Central Asia and East Asia. Two major dispersal events occurred probably during interglacial periods (around 0.8 and 0.4 Ma, respectively) when climatic conditions were analogous to present-day status, under which the scorpion achieved its maximum distributional range. M. mongolicus underwent demographic expansion during the Last Glacial Maximum, although the predicted distributional areas were smaller than those at present and during the Last Interglacial. Development of desert ecosystems in northwest China incurred by intensified aridification might have opened up empty habitats that sustained population expansion. Our results extend the spatiotemporal dimensions of trans-Eurasia faunal exchange and suggest that species' adaptation is an important determinant of their phylogeographic and demographic responses to climate changes., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

Peach (Prunus persica (L.) Batsch) is one of the most popular fruits grown in Northern China. In July 2021, a fruit rot outbreak on the peach cultivar "Yonglian Sweet" occurred after unusual rains in Baoding, Hebei Province, China. Sixty peach trees from three orchards were assessed, and a 30% disease incidence was estimated. The disease initiated as a small concave spot on the fruit surface expanding circularly rotting the fruit (3-5 cm deep) with the appearance of grayish-white mycelia (Figure S1A). The infected fruit did not disintegrate but turned light brown. To identify the pathogen, 20 infected fruits were collected, and fruit tissues from lesion margins were inoculated on the potato dextrose agar (PDA) medium. A total of 15 fungal pure cultures with highly similar morphological characteristics were obtained by the hyphal-tipping method. The fungal culture formed smooth-edged colonies of extensive, dense, wooly aerial mycelium, with color changing from sienna to luteous, and to grayish-white along the radius of colonies (Figure S1B) Chlamydospores were extensive and developed micro-sclerotia after 20 d of growth. The conidiophore produced three branches in a "broom" shape, with the primary branch ranging 7.5-25.0 μm in length, the secondary branch 5.5-15.5 μm, and the tertiary branch 10-12.5 μm (N = 30). The top of the tertiary branch tapered and produced conidia. Conidia were colorless and culm-like, 40.0-57.5 μm long and 3.8-6.25 μm wide (N = 30). Hyphae occasionally produced spherical chlamydospores with a diameter of around 7.5 μm (N = 30). Conidia germinated after 12 h in moist conditions, and germ tubes originated from multiple points on the conidia. Based on these morphological features, the isolated fungus was identified as Calonectria spp. (Lombard et al. 2010). Six loci, including ITS, act, cmdA, his3, tef1, and tub2, were amplified and sequenced for molecular identification of an isolate F099 using primers listed in Table S1. The obtained ITS (528 bp, GenBank accession no. OL635556), act (263 bp, OL694221), cmdA (470 bp, OL694222), his3 (432 bp, OL694223), tef1 (487 bp, OL694224), and tub2 (535 bp, OL694225) sequences showed 100% similarity to the ex-type strain of Calonectria canadiana, CMW 23673 (accession nos. MT359667, MT334976, MT335206, MT335446, MT412737, and MT412958, respectively; Figure S1D) (Kang et al. 2001, Lechat et al. 2010, Liu et al. 2020). The isolate F099 of C. canadiana was further subjected to pathogenicity tests. Koch's postulates were performed by placing three mycelial disks (ten-day old, 5 mm) with conidia on the sterile needle-acupunctured surface of healthy fruits of the peach cultivar "Yonglian Sweet" (N= 10). Mock inoculations with sterile PDA disks were served as a control. All the inoculated fruits were kept in a moist chamber (25℃, 16-h light and 8-h dark period). The inoculation assay was repeated twice. Rotting symptoms developed on all the inoculated fruits about 5 days post-inoculation (dpi) and grayish-white mycelia appeared around ten days post inoculation while mock inoculated fruits did not show any rotting. The pathogen of interest was re-isolated from the inoculated fruits and validated as C. canadiana by ITS and tef1 sequences. All above evidence collectively indicates that the fungal pathogen causing the peach fruit rot is C. canadiana. The new host plant and new geographic distribution reported here will inform future management of this fungal species.

The study of short-term dynamics of soil moisture in the dry-hot valley area during rainfall process will help identify soil hydrological function. In this study, we analyzed the short-term responses of soil moisture to rainfall in Huajiang dry-hot valley of Guizhou, using in-situ monitoring method to yield high-frequency soil moisture monitoring data of different slope positions. The results showed that, during the whole monitoring period, soil moisture at each layer was at a moderate variation level (15.2%≤coefficient of variation CV≤29.7%), for both upper slope and middle slope. The fluctuation range of soil moisture of the upper slope (CV=21.1%) was greater than that of the middle slope (CV=19.1%), and that of the 0-5 cm soil layer (CV=26.2%) was greater than 20-40 cm layer (CV=16.5%). Compared with the middle slope, soil moisture of the upper slope had a faster response to rainfall. The supplement amount of rainfall was bigger and the supplement speed of rainfall was faster at the upper slope than that at the middle slope. The difference between the supplement speed and the depletion speed of soil moisture of the upper slope (2.3%·h -1 ) was greater than that of the middle slope (1.8%·h -1 ). With the increase of soil depth, the responses of soil moisture to rainfall in subsoil layer was earlier or synchronous with that in topsoil layer. When the supplement amount of soil moisture decreased and the supplement speed slowed down, the depletion speed slowed down. Compared with the middle slope, soil at the upper slope had greater water infiltration capacity and better water retention capacity. The responses of soil moisture to rainfall in dry-hot valley were influenced by micro-environment and microclimate, and the rapid recharge of dominant flow at rock-soil interface accelerated the response speed of subsoil moisture to rainfall, which made the slopes in this area easier to form mixed runoff generation mechanism.

Objective: To explore the effectiveness and feasibility of dexamethasone combined with oxybuprocaine hydrochloride gel on the prevention of postoperative sore throat after nasal endoscopy., Methods: In the study, 60 patients with American Society of Anesthesiologist (ASA) physical statuses Ⅰ to Ⅱ, aged 18 to 72 years, scheduled for elective nasal endoscope surgery under general anesthesia requiring endotracheal intubation were randomly divided into dexamethasone combined with oxybuprocaine hydrochloride gel group (G group, n =30) and control group (C group, n =30). The patients in the G group received dexamethasone 0.1 mg/kg before induction and the oxybuprocaine gel was applied to the endotracheal catheter cuff and the front end within 15 cm. The patients in the C group received the same dose of saline and the saline was applied to the endotracheal catheter cuff and the front end within 15 cm. Then, all the patients in the two groups received the same induction and anesthesia maintainance. The operation time, anesthesia time, emergence time, extubation time and departure time were recorded. The intraoperative infusion volume, blood loss volume, propofol, remifentanil, rocuronium dosage were also recorded. The adverse reactions such as intraoperative hypotension, bradycardia and postoperative agitation were recorded. The postoperative sore throat score was recorded at the end of operation and 4 h, 8 h, 12 h, and 24 h after operation., Results: Compared with the C group, the emergence time [(8.4±3.9) min vs . (10.8±4.7) min], extubation time [(8.8±3.7) min vs . (11.9±4.8) min], and departure time [(20.0±5.3) min vs . (23.0±5.8) min] were significantly shorter, and the propofol dosage [(11.8±1.8) mg/kg vs . (15.9±4.6) mg/kg], remifentanil dosage [(10.9±4.7) μg/kg vs . (14.1±3.6) μg/kg] were significantly less in the G group, and there was no difference of rocuronium dosage in the two groups. Compared with the C group the incidence of intraoperative hypotension [10%(3/30) vs . 30%(9/30)], bradycardia [16.7%(5/30) vs . 20%(6/30)] and postoperative agitation [6.7%(2/30) vs . 23.3%(7/30)] were significantly lower in the C group. The postoperative sore throat score at the end of operation, 4 h, 8 h, 12 h and 24 h after operation in the G group were significantly lower than in the C group respectively [0 (0, 1) vs . 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs . 1 (1, 2), 0 (0, 0) vs . 1 (0.75, 1), 0 (0, 0) vs . 1 (0, 1)]., Conclusion: Dexamethasone combined with oxybuprocaine hydrochloride gel was effective and feasible on the prevention of postoperative sore throat after nasal endoscopy.

Many lacewing species (Insecta: Neuroptera) are important predators of pests with great potential in biological control. So far, there is no chromosome-level published genome available for Neuroptera. Here we report a high-quality chromosome-level reference genome for a green lacewing species Chrysopa pallens (Neuroptera: Chrysopidae), which is one of the most important insect natural enemies used in pest biocontrol. The genome was sequenced using a combination of PacBio and Hi-C technologies and assembled into seven chromosomes with a total size of 517.21 Mb, occupying 96.07% of the genome sequence. A total of 12,840 protein-coding genes were identified and approximately 206.21 Mb of repeated sequences were annotated. Phylogenetic analyses indicated that C. pallens diverged from its common ancestor with Tribolium castaneum (Coleoptera) approximately 300 million years ago. The gene families involved in digestion, detoxification, chemoreception, carbohydrate metabolism, immunity, nerves and development were significantly expanded, revealing the potential genomic basis for the polyphagia of C. pallens and its role as an excellent biocontrol agent. This high-quality genome of C. pallens will provide an important genomic resource for future population genetics, evolutionary and phylogenetic investigations of Chrysopidae as well as comparative genomic studies of Neuropterida and other insects., (© 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg -1 ) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways., Competing Interests: None

Photoactive metal ions doping is an efficient way to modulate the photophysical properties of perovskite. Herein, we report a zero-dimensional (0D) InCl 6 (C 4 H 10 SN) 4 ·Cl:Sb 3+ by doping Sb 3+ into InCl 6 (C 4 H 10 SN) 4 ·Cl , which undergoes a significant enhancement of the emission peak at 550 nm with photoluminescence quantum yield boosting from 20% to 90%. Interestingly, a red-shifted emission is observed on InCl 6 (C 4 H 10 SN) 4 ·Cl:Sb 3+ upon exposure to ethanol and DMF vapor with the emission peak red-shifted from 550 to 580 and 600 nm, respectively. Furthermore, the transformation is reversed after drying the vapor-exposed InCl 6 (C 4 H 10 SN) 4 ·Cl:Sb 3+ at ambient conditions. Detailed characterizations reveal that the crystal packing and structure distortion account for the reversible luminescent vapochromism. Thanks to the superior stability and feasible transformation of InCl 6 (C 4 H 10 SN) 4 ·Cl:Sb 3+ at ambient conditions, a DMF sensor was fabricated by coating the mixture of InCl 6 (C 4 H 10 SN) 4 ·Cl:Sb 3+ and PMMA into patterned substrate, which exhibits an obvious luminescent change upon release and uptake of DMF and excellent stability and producibility in several cycles.

Background: Gastric cancer is a highly heterogeneous disease and its traditional histopathological classification is difficult to meet clinical needs. Oxaliplatin is an antitumor drug with high efficiency and low toxicity. Therefore, the insensitivity or secondary drug resistance of oxaliplatin to gastric cancer is vital for tumor progression. The aim of this study was to investigate the sensitivity of gastric cancer cells to oxaliplatin after ARID1A (AT-rich interactive domain1A gene) gene silencing., Methods: MGC-803 and AGS cells were selected as gastric cancer cells for study. ARID1A protein and mRNA expression was detected by Western blot and quantitative reverse-transcription PCR (qRT-PCR). The short hairpin RNA (shRNA) fragment of ARID1A gene silencing was constructed and introduced into gastric cancer cells. The cell proliferation activity was calculated using CCK8 and the IC50 was calculated. The flow cytometry was used to detect the cell cycle and apoptosis rate. The ability of cell invasion was detected by transwell method. Cells were treated with different concentrations of oxaliplatin., Results: The proliferation of gastric cancer cells was promoted by ARID1A gene silencing (P<0.01), the quantity of cells in S phase increased (P<0.05), and the invasive ability increased (P<0.05). After treatment with oxaliplatin at different concentrations, ARID1A gene silencing reduced the inhibition rate of oxaliplatin on gastric cancer cells and apoptosis rate (P<0.05), and increased IC 50 (P<0.01)., Conclusions: ARID1A gene silencing, a factor promoting proliferation of gastric cancer cells, would reduce the sensitivity of gastric cancer cells to oxaliplatin, which can provide a basis for the exploration of targeted drugs for individualized treatment of gastric cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-2384). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estimations and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10 -4 per site per year with a 95% confidence interval (CI) of [8.61 × 10 -4 , 8.77 × 10 -4 ], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95% CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism of SARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081., (Copyright © 2021 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the effects of IFNG-AS1 and ANRIL on intestinal epithelial cells and their relationship with colitis., Patients and Methods: From May 2017 to May 2019, 118 colitis patients admitted to our hospital were selected as the research group (RG), and 124 healthy controls were selected as the control group (CG). In addition, the normal intestinal epithelial cells HIEC and HIEC-6 were purchased to detect the IFNG-AS1 and ANRIL in the peripheral blood of patients in the two groups, and the effects of IFNG-AS1 and ANRIL on the intestinal epithelial cells were analyzed., Results: IFNG-AS1 and ANRIL were highly expressed in colitis (p<0.050), and their combined detection had good diagnostic value for the occurrence of colitis and complications (p<0.050). In intestinal epithelial cells transfected with IFNG-AS1 and ANRIL, it was found that inhibition of IFNG-AS1 and ANRIL remarkably increased the proliferation and decreased the apoptosis of intestinal epithelial cells (p<0.050)., Conclusions: IFNG-AS1 and ANRIL are highly expressed in colitis, and inhibiting their expression can promote the proliferation of intestinal epithelial cells and reduce apoptosis, which may be potential therapeutic targets for Crohn's colitis in the future.

Background: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact., Case Presentation: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother's family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother's family before they got back. His younger brother and one of his brother's children visited Wuhan on 5 January and came home on 6 January 2020., Conclusions: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.

Background: Obesity is a global epidemic disease that increases the risk of metabolic syndrome. However, therapeutic drugs for obesity are still scarce. In recent years, peptides have been identified as new biological regulators. RIFV (R-I-F-V-P-I-K-G-R-P-A-P), a novel active peptide from our peptide database., Methods: We performed oil red O staining and triglyceride measurement to analyze the influence of RIFV on white preadipocytes differentiation. Then the effects of RIFV on cell proliferation, apoptosis and cell cycle were determined by using CCK-8 assay and flow cytometry. The mRNA and protein levels of adipogenesis-related genes were respectively detected by qRT-PCR and western blot. Rescue experiment was conducted to confirm whether RIFV could regulate adipocytes differentiation via targeting C/EBP-β. Finally, the luciferase reporter gene assay was performed to verify the regulation of RIFV on C/EBP-β gene., Results: RIFV was revealed to inhibit the differentiation of human white adipocytes without affecting their proliferation. Additionally, RIFV could also suppress the differentiation of mouse primary white preadipocytes isolated from inguinal fat tissues. Furthermore, RIFV may have an inhibitory effect on adipogenesis by inhibiting the regulation of the adipogenic gene C/EBP-β., Conclusions: Our results indicated that RIFV may be a novel essential regulator of adipocyte differentiation and represents a therapeutic strategy for obesity and related complications., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

A feeding trial was conducted to evaluate the effect of linseed oil (LO) on growth, plasma biochemistry, hepatic metabolism enzymes, and antioxidant capacity of juvenile largemouth bass, Micropterus salmoides. Four isonitrogenous (crude protein, 45%) and isoenergetic (gross energy, 18 MJ/kg) diets were formulated by replacing 0 (the control), 33.3%, 66.7%, and 100% of fish oil with linseed oil. Each diet was fed to three replicate groups of fish (initial body weight, 22.02 ± 0.61 g) for 8 weeks. The results indicated that fish fed diet with 100% LO substitution level had lower weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) than the other groups (P < 0.05), while feed conversion ratio (FCR) was higher compared to the other groups (P < 0.05). Feed intake (FI) and hepatosomatic index (HSI) of 66.7% LO substitution level were significantly lower than the control groups (P < 0.05). Glycogen, lipid, and non-esterified fatty acid content in the liver decreased significantly with increasing dietary LO levels (P < 0.05). Moreover, the replacement of fish oil (FO) with LO could significantly reduce the content of triglyceride (TG) and total cholesterol (TC) and the activity of alanine amiotransferase (ALT) in plasma of M. salmoides (P < 0.05). There were significant differences in hepatic metabolism enzymes in fish fed diets with different dietary LO levels. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR-α) activities in liver significantly increased with increasing dietary LO level (P < 0.05). In addition, phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBPase) activities in the liver significantly increased with decreasing dietary LO level (P < 0.05). Both the lowest superoxide dismutase (SOD) and catalase (CAT) activities in the liver were recorded in the control group (P < 0.05). Moreover, nitric oxide content, glutathione peroxidase (GPx), and inducible nitric oxide synthase (iNOS) activities in the liver significantly increased with increasing dietary LO level, while malondialdehyde (MDA) content significantly reduced. These findings demonstrated that LO can improve liver function and antioxidant ability of M. salmoides. In addition, replacing partial FO with LO cannot affect growth performance, but all substitutions inhibit growth performance of M. salmoides.

Ancestry informative markers play an important role in medical genetics and forensic analyses. Several ancestry informative SNP panels have been developed and validated that can differentiate global populations into continental or major regional groups. These global panels have served as good first-tier genetic markers; however, their performance in discriminating populations within regions appears unsatisfactory. To boost ancestry inference for regional populations, second-tier panels with more refined discrimination power among subpopulations within each of the regions need to be developed. In East Asia, Han Chinese, Japanese, and Korean show highly similar externally visible characteristics and are genetically closely related. Reliable ancestry informative genetic markers appear invaluable in discriminating these populations. In the present study, we compiled a genome-wide SNP dataset composing of 317,439 clean SNPs for a total of 1101 unrelated individuals from Han Chinese (817), Koreans (184), and Japanese (100). From this starting dataset, we developed a set of four nested ancestry informative SNP panels including 36, 59, 98, and 142 SNPs, respectively. The results of cross-validation tests indicate that these panels can discriminate the Chinese Han, Japanese, and Korean populations with overall average accuracies ranging from 90% to 99%. In the further performance assessments, these panels also manifested high sensitivity and specificity. In combination with the first-tier global panels, these second-tier panels would contribute to medical genetics and forensic research in East Asia., (© 2019 John Wiley & Sons Ltd/University College London.)

Inferring an individual's ancestry or group membership using a small set of highly informative genetic markers is very useful in forensic and medical genetics. However, given the huge amount of SNP data available from a diverse of populations, it is challenging to develop informative panels by exhaustively searching for all possible SNP combinations. In this study, we formulate it as an algorithm problem of selecting an optimal set of SNPs that maximizes the inference accuracy while minimizes the set size. Built on this conception, we develop a computational approach that is capable of constructing ancestry informative panels from multi-population genome-wide SNP data efficiently. We evaluated the performance of the method by comparing the panel size and membership inference accuracy of the constructed SNP panels to panels selected through empirical procedures in previous studies. For the membership inference of population groups including Asian, European, African, East Asian and Southeast Asian, a 36-SNP panel developed by our approach has an overall accuracy of 99.07%, and a 21-SNP subset of the panel has an overall accuracy of 95.36%. In comparison, an existing panel requires 74 SNPs to achieve an accuracy of 94.14% on the same set of population groups. We further apply the method to four subpopulations within Europe (Finnish, British, Spanish and Italian); a 175-SNP panel can discriminate individuals of those European subpopulations with an accuracy of 99.36%, of which a 68-SNP subset can achieve an accuracy of 95.07%. We expect our method to be a useful tool for constructing ancestry informative markers in forensic genetics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The next generation sequencing (NGS) technology has been playing important roles in genetic diagnosis of diseases in recent years, and serving as a technological basis of precision medicine. In analyzing NGS data, the variant annotation is an important step. In this study, we developed a computationally efficient software (BIG-Annotator) to perform functional annotation for whole-genome single nucleotide polymorphisms. BIG-Annotator integrates the widely used databases and pipelines for variant annotation of genetic diseases and tumors, and follows the 2015 ACMG-AMP Standard Guide for Interpretation and Reporting of Clinical Variants. BIG-Annotator is ten times faster than the existing software, and suitable for annotating genomic sequencing data from large samples. Here we present two analysis cases of genetic diagnosis using BIG-Annotator to show its applications.

Objective: To explore postoperative delirium (POD)risk factors for geriatric patients who suffered hip fracture under the care of orthogeriatric unit mode. Methods: Patients aged 65 years or older, who were admitted to the orthogeriatric unit in Beijing Jishuitan Hospital from April to October 2017 for hip fracture surgery, were eligible for this prospective cohort study. After univariable analysis, significant risk factors associated with POD were further evaluated with multivariable analysis, to establish independent risk factors associated with POD. Results: A total of 203 patients with an average age of 80(65-96)years were enrolled in the study. The overall incidence of POD was 9.4%(19/203)in which hyperactive and hypoactive type accounting for 84.2%(16/19)and 15.8%(3/19), respectively. Significant difference was found between POD and non-POD groups in patients' age ( P =0.003), albumin( P =0.006), TSH( P =0.018), PaCO(2) level( P =0.003), visual analogue scale (VAS )both at rest ( P =0.013)and movement( P =0.010) on post-operative day 1.The further Logistic stepwise regression analysis showed that significant differences existed between groups in age( P =0.027), albumin( P =0.003), PaCO(2)( P =0.014)and VAS at rest( P =0.002). Conclusion: The independent risk factors of POD in geriatric patients undergoing hip fracture under the orthogeriatric unit mode include patients' age, pre-operative albumin as well as PaCO(2) level and post-operative VAS at rest.

The present study examined and compared the effects of low- and high-molecular weight (MW) chitosan, a nutraceutical, on lipid metabolism in the intestine and liver of high-fat (HF) diet-fed rats. High-MW chitosan as well as low-MW chitosan decreased liver weight, elongated the small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in rats fed with HF diets. Supplementation of both high- and low-MW chitosan markedly inhibited the suppressed phosphorylated adenosine monophosphate (AMP)-activated protein kinase-α (AMPKα) and peroxisome proliferator-activated receptor-α (PPARα) protein expressions, and the increased lipogenesis/cholesterogenesis-associated protein expressions [peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element binding protein-1c and -2 (SREBP1c and SREBP2)] and the suppressed apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of rats fed with HF diets. Supplementation with both a low- and high-MW chitosan could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein-4 (Angptl4) expression in the intestines of rats fed with HF diets. In comparison between low- and high-MW chitosan, high-MW chitosan exhibits a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and an increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

An experimental trial was conducted to investigate the effects of high dietary starch levels on growth, hepatic glucose metabolism enzyme, antioxidant capacity and immune responses of largemouth bass, Micropterus salmoides. Fish (initial body weight: 16.9 ± 0.24 g) were fed three isonitrogenous and isoenergetic semi-purified diets containing 5%, 10% and 20% wheat starch, respectively. The results indicated that fish fed 5% and 10% starch diets showed significantly better weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed conversion ratio (FCR) compared with that fed 20% starch diet. Meanwhile, fish fed 20% starch diet had a significantly higher hepatic glycogen and muscle glycogen contents than those fed the other diets. The alanine amiotransferase (ALT) and aspartate transaminase (AST) activities, glucose and insulin contents in plasma increased significantly with dietary starch levels, whereas triglyceride content showed the opposite trend. In addition, the highest glucokinase (GK), pyruvate kinase (PK) and phosphofructokinase (PFK) activities in liver were also observed in fish fed 20% starch diet. However, both fructose-1,6-bisphosphatase (FBPase) and pyruvate carboxylase (PC) activities in liver decreased significantly as dietary starch levels increased. Moreover, the lower superoxide dismutase (SOD) and catalase (CAT), the higher malondialdehyde (MDA) contents in liver were observed in fish fed 20% starch diets. Compared to the 5% and 10% starch, the 20% starch could enhance the content of plasma nitric oxide (NO) and the activities of inducible nitric oxide synthase (iNOS) and alkaline phosphatase (ALP). Results demonstrate that the starch levels may affect growth performance and metabolic changes, which suggest that high-starch diets were inefficiently used as an energy source by M. salmoides juveniles. Excessive dietary starch contents could result in oxidative stress, suppress innate immunity, and thus affect the health status of M. salmoides., (Copyright © 2018. Published by Elsevier Ltd.)

Co-ancestry of human surnames and Y-chromosomes in most human populations and social groups suggests the possibility of inferring one from the other. However, such an intuitive perspective remains to be formally explored. In the present study, we develop two computational methods, based on cosine distance (d cos ) and coalescence distance (d coal ) respectively, to infer surnames from Y-STR profiles. We also survey Y-STR variations at 15 loci for 19,009 individuals of Shandong Province in China. For a total of 266 surnames included in the data set, our methods can pinpoint to a single surname with an average accuracy of 65%, and with an average accuracy higher than 80% when providing >4 candidate surnames. We also demonstrate that increasing the sample size of surnames and the number of STR loci improves the accuracy of surname inference. Our results indicate that the 15 non-duplicated Y-STR loci contain information from which surname can be reliably inferred for Chinese populations, showing a promising application in forensics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1 tg ) mice and PID1 knockout (PID1 -/- ) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1 tg mice. Consistent with these data, the PID1 -/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The phylogenetic relationships among extant gibbon species remain unresolved despite numerous efforts using morphological, behavorial, and genetic data and the sequencing of whole genomes. A major challenge in reconstructing the gibbon phylogeny is the radiative speciation process, which resulted in extremely short internal branches in the species phylogeny and extensive incomplete lineage sorting with extensive gene-tree heterogeneity across the genome. Here, we analyze two genomic-scale data sets, with ∼10,000 putative noncoding and exonic loci, respectively, to estimate the species tree for the major groups of gibbons. We used the Bayesian full-likelihood method bpp under the multispecies coalescent model, which naturally accommodates incomplete lineage sorting and uncertainties in the gene trees. For comparison, we included three heuristic coalescent-based methods (mp-est, SVDQuartets, and astral) as well as concatenation. From both data sets, we infer the phylogeny for the four extant gibbon genera to be (Hylobates, (Nomascus, (Hoolock, Symphalangus))). We used simulation guided by the real data to evaluate the accuracy of the methods used. Astral, while not as efficient as bpp, performed well in estimation of the species tree even in presence of excessive incomplete lineage sorting. Concatenation, mp-est and SVDQuartets were unreliable when the species tree contains very short internal branches. Likelihood ratio test of gene flow suggests a small amount of migration from Hylobates moloch to H. pileatus, while cross-genera migration is absent or rare. Our results highlight the utility of coalescent-based methods in addressing challenging species tree problems characterized by short internal branches and rampant gene tree-species tree discordance., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC., Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety., Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657)., Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.

Purpose: RNA helicase p68 plays an important role in organ development and maturation through tuning cell proliferation. However, the character and role of p68 in the whole wound healing process need more study., Methods: First, we characterize expression of p68 in normal rat skin development postnatal. Then, we assayed dynamic change of p68 in rat skin from different stage after injury, and explored the role of p68 in proliferation and migration of three types of wound healing related cells., Results: p68 was down-regulated during skin developmental and maturation process, up-regulated after wound, peaked on day 14 and then significantly decreased. Wound fluid enhanced wound healing related cell proliferation and up-regulated expression of p68. Conversely, reducing p68 expression by RNA interference resulted in significantly slower proliferation and migration., Conclusion: Our results define an important role of RNA helicase p68 in skin wound healing process., (Copyright © 2017. Production and hosting by Elsevier B.V.)

Competing Interests: There are no conflicts of interest.

Objective: To explore the effectiveness and feasibility of conscious sedation with a low dose of dexmedetomidine and sufentanil during multiple intestinal polyps resection in elderly patients. Methods: Sixty elderly patients who underwent multiple intestinal polyps resection in Peking University Third Hospital from Janurary to May 2016 were randomly divided into dexmedetomidine group (D group, n =30) and propofol group (P group, n =30). There were 28 males and 32 females with a mean age of (70.4±4.5) years old (range: 65-80 years old). The patients in the dexmedetomidine group received a loading dose of 0.3 μg/kg followed by a continuous infusion of 0.2-0.4 μg·kg -1 ·min -1 of dexmedetomidine and sufentanil (0.1 μg/kg) respectively.The patients in the propofol group received sufentanil 0.1 μg/kg and propofol 1.5 mg/kg and followed by a continuous infusion of 3-6 mg·kg -1 ·h -1 of propofol.Blood pressure, heart rate, pulse oxygen saturation (SpO 2 ), respiratory rate and bispectral index (BIS) were recorded at the basic status and at the beginning of operation, 10 min, 20 min, 30 min after operation, the end of operation and departure.The observer's assessment of alertness/sedation (OAA/S) scores and the clinical responses were also recorded.A statistical analysis was performed. Results: All patients in the two groups were sedated compared with baseline.The BIS values of patients in group D at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 89.6(87.8-91.0), 79.4(78.0-80.0), 76.9(75.0-80.0), 76.0(73.0-79.0) and 75.6(70.0-79.0) respectively, and those values were all significantly lower than baseline value[96.4(95.0-98.0)], ( Z =-4.645, -4.788, -4.787, -4.789, -4.789, P <0.05). The OAA/S score at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 4.5(4.0-5.0), 3.4(3.0-4.0), 3.0(3.0-3.0), 3.5(3.0-4.0) and 3.3(3.0-4.0) respectively, and were significantly lower than baseline score [4.8(5.0-5.0)] ( Z =-2.828, -4.862, -5.031, -4.420, -4.710, P <0.05). The BIS value of patients in group P at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 54.7(50.0-59.3), 54.8(50.0-59.3), 50.7(47.8-56.8), 54.4(51.5-58.0) and 53.7(50.0-57.3) respectively, and were significantly lower than baseline value[95.8(95.0-96.3)] ( Z =-4.786, -4.787, -4.788, -4.786, -4.786, P <0.05). The OAA/S score at beginning of the operation , 10 min, 20 min, 30 min after operation and the end of operation were 0.4(0.0-1.0), 0.4(0.0-1.0), 0.4(0.0-1.0), 0.4(0.0-1.0) and 0.4(0.0-1.0) respectively, and were significantly lower than baseline score[4.9(5.0-5.0)] ( Z =-4.927, -4.901, -4.912, -4.912, -4.901, P <0.05). The sedation state of group D were lighter than group P. The BIS value and OAA/S score at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation in group D were higher than group P ( P <0.05). The breath and circulation were more stable in group D. The mean arterial pressure, breath rate and SpO 2 at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation in group D were higher than group P ( P <0.05). There was no oxygen desaturation , hypotension and drowsiness in group D and the incidence in group P were 30.0%, 33.3% and 13.3% respectively.The emergency time and duration of stay in the PACU (post anesthesia care unit) were (2.0±1.2) and (22.0±7.4) min in group D, and they were (4.9±2.4) and (35.8±11.6) min in group P ( t =-5.839, t =-5.472, P <0.05). There was no difference in surgery time, patient satisfaction and acceptance rate of reexamination ( t =-3.031, t =-7.322, t =2.069, P >0.05). Conclusion: Conscious sedation with dexmedetomidine and sufentanil is effective and feasible in elderly patients undergoing multiple intestinal polyps resection.

Background: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China., Methods: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire., Results: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation., Conclusions: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China.

Brown adipose tissue (BAT) functions to dissipate energy in response to cold exposure or overfeeding. Counteracting obesity has been extensively considered as a promising target. Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the potential biological functions of lncRNAs during mouse brown fat cell differentiation have not been fully understood. Here, we performed lncRNA and mRNA expression profile analysis using microarray technology and identified 1064 lncRNAs with differential expression (fold change| ≥4, p ≤ 0.01) on day 0 and day 8 during differentiation. Furthermore, candidate lncRNAs were characterized by comprehensive examination of their genomic context, gene ontology (GO) enrichment of their associated protein-coding genes and pathway analysis. We identified three lncRNAs (Gm15051, Tmem189 and Cebpd) associated with their flanking coding genes (Hoxa1, C/EBPβ and C/EBPδ), which participated in adipose commitment. Collectively, our findings indicated lncRNAs are involved in mouse BAT development and provide potential targets for obesity therapy.

Background and Aims: It remains a challenge to prevent the local recurrence or distant metastasis of gastric carcinoma after D2 gastrectomy. Cytokine-induced killer (CIK) cells have shown promising activity against solid tumors in vitro and in vivo. We investigated the effect of adjuvant chemotherapy combined with autologous CIK therapy after D2 gastrectomy compared with adjuvant chemotherapy alone after D2 gastrectomy in patients with stage II-III gastric cancer., Methods: From January 2009 to December 2011, 226 patients with stage II-III gastric cancer who had had curative D2 gastrectomy were enrolled. Eighty-nine patients (CIK group) received adjuvant chemotherapy combining with autologous CIK therapy and 137 patients (control group) received adjuvant chemotherapy alone. Disease-free survival (DFS) and overall survival (OS) were evaluated., Results: Patients in the CIK group had longer DFS and OS than patients in the control group (DFS 41.0 months vs. 32.0 months, OS 45.0 months vs. 44.0 months, by log-rank test P = 0.006 and P = 0.028, respectively). In subgroup analysis, no significant differences in DFS and OS were observed between the two groups for the patients with stages II disease. Patients with stage III disease in the CIK group had longer median DFS and OS than patients in the control group (P = 0.031 and P = 0.038, respectively). In multivariate analysis, the stage and the interaction of stage and CIK therapy were independent prognostic factors for DFS and OS., Conclusions: The data suggest that adjuvant chemotherapy combined with autologous CIK therapy can improve prognosis for gastric carcinoma patients after D2 gastrectomy, especially for the patients with stage III disease.

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. MiR-1908 is a recently identified miRNA that is highly expressed in human adipocytes. However, it is not known what role of miR-1908 is involved in the regulation of human adipocytes. In this study, we demonstrate that the level of miR-1908 increases during the adipogenesis of human multipotent adipose-derived stem (hMADS) cells and human preadipocytes-visceral. Overexpression of miR-1908 in hMADS cells inhibited adipogenic differentiation and increased cell proliferation, suggesting that miR-1908 is involved in the regulation of adipocyte cell differentiation and metabolism, and, thus, may have an effect on human obesity.

Obesity has become a global public health problem associated with complications including type 2 diabetes, cardiovascular disease, and several cancers. Adipocyte differentiation (adipogenesis) plays an important role in obesity and energy homeostasis. Adipose tissue secretes multiple cytokines and adipokines which can cause the complications of obesity, especially insulin resistance. TNF-α, IL-6, leptin, and resistin have been identified as the main regulators of obesity and insulin activity. miR-378 is highly induced during adipogenesis and has been reported to be positively regulated in adipogenesis. In the current study, matured human adipocytes were treated with TNF-α, IL-6, leptin, or resistin on the 15th day after the induction of human pre-adipocyte differentiation. We demonstrated that TNF-α, IL-6, and leptin upregulated miR-378 expression indicating that miR-378 probably is a novel mediator in the development of insulin resistance related to obesity.