Genomic insights into the formation of human populations in East Asia.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.

TTLL1 and TTLL4 polyglutamylases are required for the neurodegenerative phenotypes in pcd mice.

Polyglutamylation is a dynamic posttranslational modification where glutamate residues are added to substrate proteins by 8 tubulin tyrosine ligase-like (TTLL) family members (writers) and removed by the 6 member Nna1/CCP family of carboxypeptidases (erasers). Genetic disruption of polyglutamylation leading to hyperglutamylation causes neurodegenerative phenotypes in humans and animal models; the best characterized being the Purkinje cell degeneration (pcd) mouse, a mutant of the gene encoding Nna1/CCP1, the prototypic eraser. Emphasizing the functional importance of the balance between glutamate addition and elimination, loss of TTLL1 prevents Purkinje cell degeneration in pcd. However, whether Ttll1 loss protects other vulnerable neurons in pcd, or if elimination of other TTLLs provides protection is largely unknown. Here using a mouse genetic rescue strategy, we characterized the contribution of Ttll1, 4, 5, 7, or 11 to the degenerative phenotypes in cerebellum, olfactory bulb and retinae of pcd mutants. Ttll1 deficiency attenuates Purkinje cell loss and function and reduces olfactory bulb mitral cell death and retinal photoreceptor degeneration. Moreover, degeneration of photoreceptors in pcd is preceded by impaired rhodopsin trafficking to the rod outer segment and likely represents the causal defect leading to degeneration as this too is rescued by elimination of TTLL1. Although TTLLs have similar catalytic properties on model substrates and several are highly expressed in Purkinje cells (e.g. TTLL5 and 7), besides TTLL1 only TTLL4 deficiency attenuated degeneration of Purkinje and mitral cells in pcd. Additionally, TTLL4 loss partially rescued photoreceptor degeneration and impaired rhodopsin trafficking. Despite their common properties, the polyglutamylation profile changes promoted by TTLL1 and TTLL4 deficiencies in pcd mice are very different. We also report that loss of anabolic TTLL5 synergizes with loss of catabolic Nna1/CCP1 to promote photoreceptor degeneration. Finally, male infertility in pcd is not rescued by loss of any Ttll. These data provide insight into the complexity of polyglutamate homeostasis and function in vivo and potential routes to ameliorate disorders caused by disrupted polyglutamylation.

The distinct initiation sites and processing activities of TTLL4 and TTLL7 in glutamylation of brain tubulin.

Mammalian brain tubulins undergo a reversible posttranslational modification-polyglutamylation-which attaches a secondary polyglutamate chain to the primary sequence of proteins. Loss of its erasers can disrupt polyglutamylation homeostasis and cause neurodegeneration. Tubulin tyrosine ligase like 4 (TTLL4) and TTLL7 were known to modify tubulins, both with preference for the ß-isoform, but differently contribute to neurodegeneration. However, differences in their biochemical properties and functions remain largely unknown. Here, using an antibody-based method, we characterized the properties of a purified recombinant TTLL4 and confirmed its sole role as an initiator, unlike TTLL7, which both initiates and elongates the side chains. Unexpectedly, TTLL4 produced stronger glutamylation immunosignals for α-isoform than ß-isoform in brain tubulins. Contrarily, the recombinant TTLL7 raised comparable glutamylation immunoreactivity for two isoforms. Given the site selectivity of the glutamylation antibody, we analyzed modification sites of two enzymes. Tandem mass spectrometry analysis revealed their incompatible site selectivity on synthetic peptides mimicking carboxyl termini of α1- and ß2-tubulins and a recombinant tubulin. Particularly, in the recombinant α1A-tubulin, a novel region was found glutamylated by TTLL4 and TTLL7, that again at distinct sites. These results pinpoint different site specificities between two enzymes. Moreover, TTLL7 exhibits less efficiency to elongate microtubules premodified by TTLL4, suggesting possible regulation of TTLL7 elongation activity by TTLL4-initiated sites. Finally, we showed that kinesin behaves differentially on microtubules modified by two enzymes. This study underpins the different reactivity, site selectivity, and function of TTLL4 and TTLL7 on brain tubulins and sheds light on their distinct role in vivo.

Resistive Memristors Using Robust Electropolymerized Porous Organic Polymer Films as Switchable Materials.

Porous organic polymers (POPs) with inherent porosity, tunable pore environment, and semiconductive property are ideally suitable for application in various advanced semiconductor-related devices. However, owing to the lack of processability, POPs are usually prepared in powder forms, which limits their application in advanced devices. Herein, we demonstrate an example of information storage application of POPs with film form prepared by an electrochemical method. The growth process of the electropolymerized films in accordance with the Volmer-Weber model was proposed by observation of atomic force microscopy. Given the mechanism of the electron transfer system, we verified and mainly emphasized the importance of porosity and interfacial properties of porous polymer films for memristor. As expected, the as-fabricated memristors exhibit good performance on low turn-on voltage (0.65 ± 0.10 V), reliable data storage, and high on/off current ratio (104). This work offers inspiration for applying POPs in the form of electropolymerized films in various advanced semiconductor-related devices.

Photosynthetic mechanism of maize yield under fluctuating light environments in the field.

The photosynthetic mechanism of crop yields in fluctuating light environments in the field remains controversial. To further elucidate this mechanism, we conducted field and simulation experiments using maize (Zea mays) plants. Increased planting density enhanced the light fluctuation frequency and reduced the duration of daily high light, as well as the light-saturated photosynthetic rate, biomass, and yield per plant. Further analysis confirmed a highly significant positive correlation between biomass and yield per plant and the duration of photosynthesis related to daily high light. The simulation experiment indicated that the light-saturated photosynthetic rate of maize leaves decreased gradually and considerably when shortening the daily duration of high light. Under an identical duration of high light exposure, increasing the fluctuation frequency decreased the light-saturated photosynthetic rate slightly. Proteomic data also demonstrated that photosynthesis was mainly affected by the duration of high light and not by the light fluctuation frequency. Consequently, the current study proposes that an appropriate duration of daily high light under fluctuating light environments is the key factor for greatly improving photosynthesis. This is a promising mechanism by which the photosynthetic productivity and yield of maize can be enhanced under complex light environments in the field.

Genome-wide identification of heat shock protein gene family and their responses to pathogen challenge in Trachinotus ovatus.

Heat Shock Proteins (HSPs) are a widely distributed family of proteins produced in response to heat and other stresses. To develop a deeper understanding of the mechanisms governing expression of HSPs in the bony fish Trachinotus ovatus, we carried out a whole genome analysis and identified 43 HSP genes. Based on their phylogenetic relationships with Danio rerio, Seriola dumerili, and Seriola lalandi, they were divided into four subfamilies: HSP20, HSP60, HSP70, and HSP90. We performed an analysis of the predicted physicochemical properties and subcellular localization of proteins encoded by these genes. The chromosomal localization results showed that the HSP genes are distributed across 20 chromosomes of T. ovatus.These genes were found to be expressed in different tissues, and they showed differential expression in the immune response against Streptococcus agalactiae. However, there was no significant differential expression in the different skin tissue locations of T. ovatus after infection by Cryptocaryon irritans Brown. This study provides basic information for further research on the evolution and structure and function of HSPs in teleosts.

Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Convolutional neural network models applied to neuronal responses in macaque V1 reveal limited nonlinear processing.

Computational models of the primary visual cortex (V1) have suggested that V1 neurons behave like Gabor filters followed by simple nonlinearities. However, recent work employing convolutional neural network (CNN) models has suggested that V1 relies on far more nonlinear computations than previously thought. Specifically, unit responses in an intermediate layer of VGG-19 were found to best predict macaque V1 responses to thousands of natural and synthetic images. Here, we evaluated the hypothesis that the poor performance of lower layer units in VGG-19 might be attributable to their small receptive field size rather than to their lack of complexity per se. We compared VGG-19 with AlexNet, which has much larger receptive fields in its lower layers. Whereas the best-performing layer of VGG-19 occurred after seven nonlinear steps, the first convolutional layer of AlexNet best predicted V1 responses. Although the predictive accuracy of VGG-19 was somewhat better than that of standard AlexNet, we found that a modified version of AlexNet could match the performance of VGG-19 after only a few nonlinear computations. Control analyses revealed that decreasing the size of the input images caused the best-performing layer of VGG-19 to shift to a lower layer, consistent with the hypothesis that the relationship between image size and receptive field size can strongly affect model performance. We conducted additional analyses using a Gabor pyramid model to test for nonlinear contributions of normalization and contrast saturation. Overall, our findings suggest that the feedforward responses of V1 neurons can be well explained by assuming only a few nonlinear processing stages.

Discovery of new triterpenoids from Leptopus clarkei and their antiproliferative activity on cancer cells.

Two new triterpenoids (1-2), along with six known analogues (3-8) were obtained from the dried whole plant of Leptopus clarkei. Compound 1 is a 3,4-seco-lupane-type triterpenoid, and compound 2 is a phenylpropanoid-conjugated pentacyclic triterpenoid possessing trans-p-coumaroyl unit attached to oleanane-type skeleton. This is the first report on chemical investigation of the L. clarkei, and the triterpenoid derivatives were found in this plant for the first time. The structures of the new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. Additionally, the isolated compounds were evaluated for theircytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Notably, compound 2 exhibited the most significant antiproliferative activity with IC50 less than 20 µM for four cancer lines.

CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.

BACKGROUND: The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) - polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. RESULTS: In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP - CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. CONCLUSION: These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

Two new cassane diterpenoids from the seed kernels of Caesalpinia sinensis.

Two new cassane diterpenoids, sucupiranin MN (1) and sucupiranin ML (2), together with two known compounds sucutinirane C (3) and deacetylsucutinirane C (4) were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated by means of analysis of comprehensive spectroscopic data, especially HRESIMS and 1D/2D NMR spectroscopy. Compounds 1-4 are typical furan-type cassane derivatives with an aromatized C ring. Biological evaluation revealed that compounds 1-4 at the concentration of 10 µM could inhibit the overproduction of NO in LPS-stimulated RAW 264.7 macrophages.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

Systematically analysis of decompensated cirrhotic patients with spontaneous bacterial peritonitis to identify diagnostic and prognostic indexes.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP. METHODS: We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients' clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed. RESULTS: A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child-Pugh score (P < 0.05). Patients with SBP had a greater proportion of malignancies than those without SBP(P < 0.05). The majority of laboratory test indicators differed significantly between patients with and without SBP (P < 0.05). Albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were found to be independently associated with SBP in decompensated cirrhotic patients using LASSO algorithms, and logistic regression analysis. The model established by the three indices showed a high predictive value with an AUC of 0.808. Furthermore, increased neutrophils, ALP, and C-reactive protein-to-albumin ratio (CAR) were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a greater predictive value for cirrhotic patients. CONCLUSIONS: The present study identified FNR as a novel index in the diagnosis of SBP in decompensated patients with cirrhosis. A model based on neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with decompensated cirrhosis.

Theoretical study of the tuning role of ß-methylthio or ß-methylselenyl on the charge-transport properties of acenedithiophenes derivatives.

To date, the manipulation of intermolecular nonconjugation interactions in organic crystals is still a great challenge due to the complexity of weak intermolecular interactions. Here we designed molecules substituted by ß-methylselenyl on naphtho[1,2-b:5,6-b']dithiophene and anthra[2,3-b:6,7-b']dithiophene, respectively (anti-ß-MS-NDT, anti-ß-MS-ADT), which together with anti-ß-MS-BDT synthesized experimentally all exhibited 2D brickwork π-stacking. Moreover, their maximum molecular carrier mobilities reached 3.30 and 16.46 cm2 V-1 s-1. These results indicated that the substitution of ß-methylselenyl could be a strategy to directionally adjust the parent herringbone stacking into 2D brickwork π-stacking. Hirshfeld surface analysis and symmetry-adapted perturbation theory (SAPT) were used to investigate the nonconjugated interactions in the pitched π-stacking formed by the ß-methylthio-substituted acenedithiophene derivatives and the 2D brickwork π-stacking of the ß-methylselenyl-substituted ones; wherein, the steric hindrance caused by the introduction of the substituents promoted Csp2-Csp2⋯π interactions to replace Csp2-H⋯π to stabilize the face-to-face stacking. Moreover, by calculating the decomposition energy of the intermediate state model of the molecular stacking mode that may exist in the replacement conversion process, it was found that the energy of this intermediate state was larger than that of the actual ones, finally confirming the inevitability of the actual existence in this stacking. In addition, because of the reduction in intensity of the special vibration modes, it could be found that the ß-methylselenyl substitution showed better phonon assistance than ß-methylthio substitution in terms of dynamic disorder. This study is a further step toward fully understanding the relationship between intermolecular interactions and regulation of the molecular stacking.

Gremlin-1 promotes IL-1ß-stimulated chondrocyte inflammation and extracellular matrix degradation via activation of the MAPK signaling pathway.

The role and mechanism of Gremlin-1 in osteoarthritis (OA) were expected to be probed in this study. Firstly, an in vitro OA model was constructed by stimulating human chondrocyte cell line CHON-001 with IL-1ß. Next, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were utilized for assessing the effect of IL-1ß with different concentrations (5, 10, and 20 ng/mL) on the activity and Gremlin-1 messenger RNA of CHON-001 cells, respectively. Besides, the influence of knocking down/over-expressing Gremlin-1 on the inflammatory factors (IL-6, TNF-α, IL-18 and PGE2), oxidative stress-related substances (malondialdehyde [MDA]; superoxide dismutase [SOD]; lactate dehydrogenase [LDH]), extracellular matrix (ECM) degradation-related proteins, and mitogen-activated protein kinase (MAPK) pathway proteins in IL-1ß-stimulated CHON-001 cells were tested by enzyme-linked immunosorbent assay, related kits, qRT-PCR, and western blot, respectively. IL-1ß inhibited CHON-001 cell proliferation and upregulated Gremlin-1 expression in a concentration-dependent manner. Overexpression of Gremlin-1 increased the IL-6, TNF-α, IL-18, PGE2, and MDA levels, enhanced the LDH activity, and decreased the SOD activity in IL-1ß-induced CHON-001 cells; while the effect of Gremlin-1 knockdown on the above factors was in contrast with that of the overexpression. Furthermore, overexpression of Gremlin-1 upregulated protein expression of matrix metalloproteinase (MMP)-3, MMP-13, and ADAMTS4 while downregulated protein expression of collagen III, aggrecan, and SOX-9 in IL-1ß-stimulated CHON-001 cells. Besides, overexpression of Gremlin-1 increased the p-p38/p38 value while decreased the p-JNK/JNK value in L-1ß-stimulated CHON-001 cells; however, knockdown of Gremlin-1 reversed the above results. Gremlin-1 may promote IL-1ß-stimulated CHON-001 cell inflammation and ECM degradation by activating the MAPK signaling pathway.

Negative life events and aggression among Chinese rural left-behind adolescents: do self-esteem and resilience mediate the relationship?

BACKGROUND: Left-behind adolescents (LBAs) are adolescents aged 11-18 years who are separated from their parents and left behind in local cities by one or both parents for a period of more than 6 months. LBAs in rural areas are likely to engage in aggressive behavior, which can affect interpersonal relationships, reduce academic performance, and even lead to anxiety and depression. To our knowledge, no studies have examined the mediating effect of resilience and self-esteem on the relationship between negative life events and aggression among Chinese rural LBAs. Therefore, this study aimed to explore the relationship between negative life events and aggression among Chinese rural LBAs and how self-esteem and resilience mediate the association. METHODS: Using a stratified random sampling method, 1344 LBAs in Hunan Province of China were investigated. Information was collected by a self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale and Aggression Scales to assess the psychology of LBAs. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. RESULTS: Negative life events were significantly related to self-esteem (r = - 0.338), resilience (r = - 0.359), and aggression (r = 0.441). Aggression was directly affected by self-esteem (ß = - 0.44) and resilience (ß = - 0.34). Negative life events were not only directly related to aggression (ß = 0.34, 95% CI: 0.275 ~ 0.398) but also showed an indirect effect on aggression through self-esteem and resilience. The direct effect, total effect and indirect effect of negative life events on aggression through self-esteem and resilience were 0.3364, 0.4344 and 0.0980, respectively. The mediating effect of self-esteem and resilience accounted for 22.56% of the relationship between negative life events and aggression. CONCLUSIONS: We found that self-esteem and resilience mediated most negative life events on aggression. It is imperative for educators and families to improve LBAs' self-esteem and resilience to reduce the occurrence of aggression. Future intervention studies should be designed to strengthen self-esteem and resilience.

Theoretical insight on the charge transport properties: The formation of "head-to-tail" and "head-to-head" stacking of asymmetric aryl anthracene derivatives.

Organic semiconductors (OSCs) are widely used in flexible display, renewable energy, and biosensors, owing to their unique solid-state physical and optoelectronic properties. Among the abundant crystal library of OSCs, asymmetric aryl anthracene derivatives have irreplaceable advantages due to the interplay between their distinct π-conjugated geometry and molecular stacking as well as efficient light emission and charge transport properties that can be simultaneously utilized. However, the poor crystal stacking patterns of most asymmetric molecules limit their utility as excellent OSCs. Thus, it is crucial to clarify the structural features that enable the extremely ordered stacking and favorable electronic structure of asymmetric anthracene derivatives to become high-performance OSCs. This contribution investigates the charge transport properties of a series of asymmetric aryl anthracene derivatives to reveal the modulation factors of the molecular stacking modes and to explore the structural factors, which are beneficial to charge transport. The analysis demonstrated that the vinyl-linker facilitated the injection of hole carriers, and the alkynyl-linker effectively reduces the reorganization energy. Importantly, the linear polarizability and permanent dipole moment of a single molecule play a vital regulation to molecular stacking modes and the transfer integral of the dimer. The "head-to-head stacking" motif shows a compact stacking pattern and the maximum 2D anisotropic mobility more than 10 cm2 V-1 s-1. These findings sharpen our understanding of the charge transport properties in asymmetric organic semiconductors and are essential for developing a diverse range of high-performance OSC materials.

Sterility of Cydia pomonella by X ray irradiation as an alternative to gamma radiation for the sterile insect technique.

The codling moth Cydia pomonella is a major pest of global significance impacting pome fruits and walnuts. It threatens the apple industry in the Loess Plateau and Bohai Bay in China. Sterile insect technique (SIT) could overcome the limitations set by environmentally compatible area-wide integrated pest management (AW-IPM) approaches such as mating disruption and attract-kill that are difficult to suppress in a high-density pest population, as well as the development of insecticide resistance. In this study, we investigated the effects of X-ray irradiation (183, 366, 549 Gy) on the fecundity and fertility of a laboratory strain of C. pomonella, using a newly developed irradiator, to evaluate the possibility of X-rays as a replacement for Cobalt60 (60Co-γ) and the expanded future role of this approach in codling moth control. Results show that the 8th-day is the optimal age for irradiation of male pupae. The fecundity decreased significantly as the dosage of radiation increased. The mating ratio and mating number were not influenced. However, treated females were sub-sterile at a radiation dose of 183 Gy (20.93%), and were almost 100% sterile at a radiation dose of 366 Gy or higher. Although exposure to a radiation dose of 366 Gy resulted in a significant reduction in the mating competitiveness of male moths, our radiation biology results suggest that this new generation of X-ray irradiator has potential applications in SIT programs for future codling moth control.

Guided Isolation of New Cytotoxic Cassane Diterpenoids from Caesalpinia sappan.

Guided by an MS/MS-based molecular networking, six undescribed cassane diterpenoids and three known ones were isolated and identified from the seeds of Caesalpinia sappan. Their structures were unequivocally elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Cytotoxic evaluation showed that phanginin JA exhibited significant antiproliferative activities against human non-small cell lung cancer (A549) cells with IC50 values of 16.79±0.83 µM. Further flow cytometry analysis revealed that phanginin JA could exert apoptotic effect of A549 cells by arresting cell cycle in G0/G1 phase.