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Summary: The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC. This comprehensive analysis included detailed covariates such as age at diagnosis, sex, clinical stage, cancer histology, and smoking status. We report that SIRE is significantly associated with KRAS mutations, modified by sex, with SIRE-Asian patients showing lower rates of KRAS mutation, transversion substitution, and the allele-specific subtype KRASG12C compared to SIRE-White patients after adjusting for potential confounders. Moreover, GIA was found to correlate with KRAS mutations, where patients with a higher proportion of European ancestry had an increased risk of KRAS mutations, especially more transition substitutions and KRASG12D. Notably, among SIRE-White patients, an increase in European ancestry was linked to a higher likelihood of KRAS mutations, whereas an increase in admixed American ancestry was associated with a reduced likelihood, suggesting that quantitative GIA offers additional information beyond SIRE. The association of SIRE, GIA, and their interplay with KRAS driver mutations in NSCLC highlights the importance of incorporating both into population-based cancer research, aiming to refine clinical decision-making processes and mitigate health disparities.

The copper crystal cone-shaped micro-nanostructure is used as the substrate, and the Ni–W alloy layer and Au nanolayer are plated sequentially. Instantaneous soldering with lead-free solder is realized under ultrasonic assistance at room temperature. This solves the residual stress and thermal damage caused by high melting point lead-free solder on thin chips and thermal components, and ensures the safety and reliability of electronic components. Copper-based microstructures are deposited by electrochemical methods. An amorphous Ni–W alloy layer with a thickness of 180 nm is deposited on the Cu-based microstructures by adjusting the atomic ratio of the plating solution. The Ni–W layer is further coated with a 50 nm Au layer to prevent oxidation. Solid-phase transient soldering is realized by combining the Au/Ni–W multilayer thin-film-modified Cu substructures with commercial solder (SAC305) for a holding time of 3 s at a soldering pressure of 10,000 gf (20 MPa) while ultrasonically assisted. The soldered samples are aged at 180 °C for 10 min, 30 min, and 60 min, respectively. Copper substructures with different surface modifications are subjected to destructive shear experiments with solder balls. Scanning electron microscope and X-ray fluorescence thickness gauge are used to study the microstructure, intermetallic compound (IMC) composition thickness and properties of the soldered interface and section. The cone height of the Cu-based structure is 2–4 μm, and the diameter of the bottom is 800 nm–1200 nm, which has a sharp tip and an excellent L/D ratio. The interface between the Au/Ni–W modified Cu substructure and the solder ball is almost free of holes. The average shear strength at the soldering interface is about 43.06 MPa. The fracture surface after the shear experiment basically occurs inside the solder ball matrix, which belongs to the pure toughness fracture. The interface between the Au/Ni–W-modified Cu-based structure and the solder ball is subjected to long aging treatment at 180 °C. The soldering interface showed a “bright layer”. New phases are generated on the solder side above the “bright layer”, while no new phases appear on the Cu substructure side below the “bright layer”. The copper-based microstructure is inserted into the inside of the solder ball to form an inlay and produce mechanical interlocking. Au/Ni–W alloy modification layer can effectively improve the surface hardness of copper-based structures. This creates a large hardness difference with soft solder and enables the formation of fewer holes in the insertion solder. Amorphous Ni–W alloys are prone to form dense oxide films during ultrasonication. The Au film modification prevents oxide generation and increases the average shear strength of the soldering interface. The Ni–W alloy layer retards the interdiffusion between Cu–Sn, blocks the excessive growth of Cu–Sn IMCs, and reduces the reliability problems caused by interface failure.

We present the first known case of a patient with BRD2::NUTM1-driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a BRD2::NUTM1 fusion led to the diagnosis of NUT carcinoma. She received multiple lines of chemotherapy with response and is still alive at 2 years postdiagnosis. This report expands on the known fusions in NUT carcinoma and highlights potential differences in patient prognosis on the basis of gene fusion partners.

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair.

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

Isolated pillars in underground mines are subjected to uniaxial stress, and the load bearing cross-section of pillars is commonly rectangularly shaped. In addition, the uniaxial compression test (UCT) is widely used for determining the basic mechanical properties of rocks and revealing the mechanism of isolated pillar disasters under unidimensional stress. The shape effects of rock mechanical properties under uniaxial compression are mainly quantitatively reflected in the specific shape ratios of rocks. Therefore, it is necessary to study the detailed shape ratio effects on the mechanical properties of rectangular prism rock specimens and isolated pillars under uniaxial compressive stress. In this study, granite, marble and sandstone rectangular prism specimens with various height to width ratios (r) and width to thickness ratios (u) were prepared and tested. The study results show that r and u have a great influence on the bearing ability of rocks, and thin or high rocks have lower uniaxial compressive strength. Reducing the level of r can enhance the u effect on the strength of rocks, and increasing the level of u can enhance the r effect on the strength of rocks. The lateral strain on the thickness side of the rock specimen is larger than that on the width side, which implies that crack growth occurs easily on the thickness side. Considering r and u, a novel strength prediction model of isolated pillars was proposed based on the testing results, and the prediction model was used for the safety assessment of 179 isolated pillars in the Xianglu Mountain Tungsten Mine.

Introduction: This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in EGFR-mutant NSCLC. Methods: Retrospective review identified 105 patients from eight institutions with advanced EGFR-mutant NSCLC treated with osimertinib 160 mg daily between October 2013 and January 2020. Radiographic responses were clinically assessed, and Kaplan-Meier analyses were used. We defined CNS disease control as the interval from osimertinib 160 mg initiation to CNS progression or discontinuation of osimertinib 160 mg. Results: Among 105 patients treated with osimertinib 160 mg, 69 were escalated for CNS progression, including 24 treated with dose escalation alone (cohort A), 34 who received dose-escalated osimertinib plus concurrent chemotherapy and/or radiation (cohort B), and 11 who received osimertinib 160 mg without any prior 80 mg exposure. The median duration of CNS control was 3.8 months (95% confidence interval [CI], 1.7–5.8) in cohort A, 5.1 months (95% CI, 3.1–6.5) in cohort B, and 4.2 months (95% CI 1.6–not reached) in cohort C. Across all cohorts, the median duration of CNS control was 6.0 months (95% CI, 5.1–9.0) in isolated leptomeningeal progression (n = 27) and 3.3 months (95% CI, 1.0–3.1) among those with parenchymal-only metastases (n = 23). Patients on osimertinib 160 mg experienced no severe or unexpected side effects. Conclusion: Among patients with EGFR-mutant NSCLC experiencing CNS progression on osimertinib 80 mg daily, dose escalation to 160 mg provided modest benefit with CNS control lasting approximately 3 to 6 months and seemed more effective in patients with isolated leptomeningeal CNS progression.

Cost-effective reefs improve the yield of sea cucumber Apostichopus japonicas cultured in ponds. The reaction to reef models was studied in laboratory experiments regarding selectivity and fitness-related behaviors (crawling, feeding and defecation) in different roughness (rough and smooth), angles (30°, 60° and 90°) and heights (3.5, 7, 10.5 and 14 cm). The present study found that significantly more sea cucumbers selected the rough model, with significantly better crawling frequency, tentacles activity frequency and defecation behavior compared with those on the smooth model. This indicates that rough materials in artificial reefs are appropriate for the fitness-related behaviors of sea cucumbers. Regarding the angles, the 30° model attracted significantly more sea cucumbers than those of 60° and 90°. Among the three angles, sea cucumbers in the 30° model showed significantly better defecation behavior, while showed higher frequencies of crawling and tentacles activity in comparison with the 90° model. In other words, the models of 30° and 60° serve as the ''toilet'' and the ''kitchen'' of sea cucumbers better in defecation and food intake. No significant difference was found in the number of sea cucumbers selecting any model of three heights. The 7-cm model sees significantly higher frequencies of crawling and tentacles activity than the ones of 3.5 and 14 cm. These results indicate that the higher reef may not necessarily be valuable in the pond culture and a shorter one may help boost the feeding efficiency of sea cucumbers.

Data from National Health and Nutrition Examination Survey (2007–2016) was used to examine the cross-sectional association between different types of coffee and caffeine intake and glucose metabolism markers. Linear regression and restricted cubic spline were adopted with adjustments for potential covariates. There was inverse association of insulin resistance with total coffee, caffeinated coffee, caffeine from coffee, and total caffeine intake (all β

Long non-coding RNAs (lncRNAs) refer to elements of genomic transcription with more than 200 nucleotides that are not translated into proteins, but have crucial roles in cancer progression. MAGI2-AS3, a novel lncRNA, has been reported to be aberrantly expressed in many solid tumors. Increasingly, studies have demonstrated that MAGI2-AS3 expression is significantly correlated with patient clinical characteristics, and that MAGI2-AS3 can regulate multiple biological processes through target-gene regulation. Furthermore, MAGI2-AS3 may serve as both a diagnostic biomarker and as a promising therapeutic target against solid tumors. In this review, we summarize the current knowledge regarding the biological functions and related molecular mechanisms of MAGI2-AS3 in solid-tumor progression. We conclude that understanding MAGI2-AS3 properties may provide new insights into the diagnoses and treatments of solid tumors.

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in ethanol-induced neurodegeneration and its association with ER stress regulation, we established a CNS-specific Manf knockout mouse model and examined the effects of MANF deficiency on ethanol-induced neuronal apoptosis and ER stress using a third-trimester equivalent mouse model. We found MANF deficiency exacerbated ethanol-induced neuronal apoptosis and ER stress and that blocking ER stress abrogated the harmful effects of MANF deficiency on ethanol-induced neuronal apoptosis. Moreover, using an animal model of ER-stress-induced neurodegeneration, we demonstrated that MANF deficiency potentiated tunicamycin (TM)-induced ER stress and neurodegeneration. A whole transcriptome RNA sequencing also supported the functionality of MANF in ER stress modulation and revealed targets that may mediate the ER stress-buffering capacity of MANF. Collectively, these results suggest that MANF is a neurotrophic factor that can protect neurons against ethanol-induced neurodegeneration by ameliorating ER stress.

Taking advantage of the seasonally appropriate water temperature in southern China is an important approach to expanding Strongylocentrotus intermedius aquaculture for the increasing market demand. However, appropriate diets remain largely uninvestigated and seed supply is in shortage, leaving the most serious problems of S. intermedius aquaculture in southern China unaddressed. Here, a feeding experiment was conducted for ∼6 months (from November 2018 to May 2019) to compare the somatic and gonadal growth, as well as gonadal development of S. intermedius (∼30 mm of test diameter) fed either macroalgae Gracilaria lemaneiformis or Saccharina japonica at the temperatures simulating water those off southern China coast (Fuzhou, 119°50′ E, 26°24′ N). Test size, wet body weight, specific growth rate, lantern size, wet gut weight and gonad yield of S. intermedius fed S. japonica were all significantly larger than those of sea urchins fed G. lemaneiformis. The present results indicate that long-term feeding G. lemaneiformis is unacceptable for aquacultural S. intermedius in southern China, because of the inefficiency of supporting somatic and gonadal growth. Saccharina japonica may suffice as a suitable diet for the aquaculture of S. intermedius in southern China. Further, spent gonads were observed in S. intermedius fed G. lemaneiformis in May 2019, meanwhile all gonads of individuals fed S. japonica remained in the premature stage. This suggests that G. lemaneiformis displays a promising potential for accelerating gonadal development of S. intermedius and subsequently supports the seed production of sea urchins in spring in southern China. The present study provides valuable information into the aquaculture management of S. intermedius in southern China.

Afatinib (Afa), a second-generation irreversible epidermal growth factor inhibitor for the development of non-small cell lung cancer, has low bioavailability and adverse reactions. Nanoscaled drug delivery systems offer promising alternatives to address these defects and improve therapeutic outcomes. In the present study, a Tf contained, redox-sensitive ligand was synthesized and used for the preparation of afatinib loaded, Tf modified redox-sensitive lipid-polymer hybrid nanoparticles (Tf-SS-Afa-LPNs). Subsequently, studies of biological experiments in vitro and in vivo were performed to investigate the therapeutic effect of the system in lung cancer. The results showed that Tf-SS-Afa-LPNs has particle size of 103.5 ± 4.1 nm and zeta potential of -21.2 ± 2.4 mV. Significantly higher drug release was observed in the presence of glutathione (GSH). The area under the plasma concentration – time curve (AUC), peak concentration (Cmax) and terminal half life (T1/2) of Tf-SS-Afa-LPNs were 866.56 mg/L.h, 25.62 ± 3.21 L/kg/h, and 43.25 ± 2.31 h. Tf-SS-Afa-LPNs exhibited the most remarkable in vivo anti-tumor efficiency efficacy, which inhibited the tumor volume from 919 mm3 to 212 mm3. Tf-SS-Afa-LPNs is a promising platform for the lung cancer treatment.

The Hedgehog (Hh) pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK) is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.

Drought is projected to intensify under warming climate and will continuously threaten global food security. Assessing the risk of yield loss due to drought is key to developing effective agronomic options for farmers and policymakers. However, little has been known about determining the likelihood of reduced crop yield under different drought conditions and defining thresholds that trigger yield loss at the regional scale in Australia. Here, we estimated the dependence of yield variation on drought conditions and identified drought thresholds for 12 Australia's key wheat producing regions with historical yield data by developing bivariate models based on copula functions. These identified drought thresholds were used to investigate drought statistics under climate change with an ensemble of 36 climate models from Coupled Model Intercomparison Project Phase 6 (CMIP6). We found that drought-induced yield loss was region-specific. The drought thresholds leading to the same magnitude of wheat yield reduction were smaller in regions of southern Queensland and larger in Western Australia mainly due to different climate and soil conditions. Drought will be more frequent and affect larger areas under future warming climates. Based on our results, we advocate for more effective crop management options, particularly in regions where wheat yield is vulnerable to drought in Australia. This will mitigate potential drought impacts on crop production and safeguard global food security.

Extensive studies have been conducted on the impact of foreign language reading anxiety on reading, primarily focusing on pedagogy and behavior but lacking electrophysiological evidence. The current study aimed to investigate the influence of foreign language reading anxiety on reading and its underlying mechanisms. The results revealed a negative correlation between foreign language reading anxiety and foreign language reading performance, irrespective of the native language. Adults with low levels of foreign language reading anxiety (LFLRA) demonstrated a significant difference in early lexical component N170 amplitude between foreign and native languages. However, this effect was not observed in adults with high levels of foreign language reading anxiety (HFLRA). In terms of N170 latency, HFLRA showed a longer N170 for the foreign language compared to the native language. Furthermore, the N170 effects were predominantly localized over the left occipitotemporal electrodes. Regarding N400 latency, a significant difference was found in LFLRA individuals between foreign and native language processing, while HFLRA individuals did not exhibit this difference. These findings suggest that HFLRA individuals experience inefficient lexical processing (such as orthography or semantics) during reading in foreign language.

Summary: Women are more vulnerable to stress and have a higher likelihood of developing mood disorders. The serotonin (5HT) system has been highly implicated in stress response and mood regulation. However, sex-dependent mechanisms underlying serotonergic regulation of stress vulnerability remain poorly understood. Here, we report that adult hippocampal neural stem cells (NSCs) of the Ascl1 lineage (Ascl1-NSCs) in female mice express functional 5HT1A receptors (5HT1ARs), and selective deletion of 5HT1ARs in Ascl1-NSCs decreases the Ascl1-NSC pool only in females. Mechanistically, 5HT1AR deletion in Ascl1-NSCs of females leads to 5HT-induced depolarization mediated by upregulation of 5HT7Rs. Furthermore, repeated restraint stress (RRS) impairs Ascl1-NSC maintenance through a 5HT1AR-mediated mechanism. By contrast, Ascl1-NSCs in males express 5HT7R receptors (5HT7Rs) that are downregulated by RRS, thus maintaining the Ascl1-NSC pool. These findings suggest that sex-specific expression of distinct 5HTRs and their differential interactions with stress may underlie sex differences in stress vulnerability.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

With an aging population and the numerous health impacts associated with old age, the identification of anti-aging drugs has become an important new research direction. Although mitochondria have been recognized to affect aging, anti-aging drugs specifically targeting the mitochondria are less well characterized. In this study, diphenyleneiodonium (DPI) was identified as a potential senomorphic drug that functions by promoting mitochondrial fission. DPI significantly reduced the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and increased the number of proliferating Ki-67 positive cells in BrdU or irradiation stress-induced senescent NIH3T3 cells or IMR90 cells and mouse embryonic fibroblasts (MEFs) replicative senescent cells. Cell cycle arrest genes and senescence-associated secretory phenotype (SASP) factors were downregulated with DPI treatment. In addition, the oxygen consumption rate (OCR) of mitochondrial respiration showed that DPI significantly reduced senescence-associated hyper OCR. Mechanistically, DPI promoted mitochondrial fission by enhancing AMPK/MFF phosphorylation and DRP1 mitochondrial translocation. Inhibition of DRP1 by Mdivi-1 abolished DPI-induced mitochondrial fission and the anti-senescence phenotype. Importantly, Eighty-eight-week-old mice treated with DPI had significantly reduced numbers of SA-β-gal positive cells and reduced expression of cell cycle arrest genes and SASP factors in their livers and kidneys. Pathological and functional assays showed DPI treatment not only reduced liver fibrosis and immune cell infiltration but also improved aged-related physical impairments in aged mice. Taken together, our study identified a potential anti-aging compound that exerts its effects through modulation of mitochondrial morphology.

Adolescence is the peak period for the onset of generalized anxiety disorder (GAD). Brain networks of cognitive and affective control in adolescents are not well developed when their exposure to external stimuli suddenly increases. Reasonable parental monitoring is especially important during this period. To examine the role of parental monitoring in the development of functional brain networks of GAD, we conducted a cross-validation-based predictive study based on the functional brain networks of 192 participants. We found that a set of functional brain networks, especially the default mode network and its connectivity with the frontoparietal network, could predict the ages of adolescents, which was replicated in three independent samples. Importantly, the difference between predicted age and chronological age significantly mediated the relationship between parental monitoring and anxiety levels. These findings suggest that inadequate parental monitoring plays a crucial role in the delayed development of specific brain networks associated with GAD in adolescents. Our work highlights the important role of parental monitoring in adolescent development.

To optimize our decisions, we may change our mind by utilizing social information. Here, we examined how changes of mind were modulated by Social Misalignment Sensitivity (SMS), egocentric tendency, and decision preferences in a decision-making paradigm including both risk and social information. Combining functional magnetic resonance imaging with computational modeling, we showed that both SMS and egocentric tendency modulated changes of mind under the influence of social information. While SMS was represented in the dorsal anterior cingulate cortex (dACC) and superior parietal gyrus (SPG) in the socially aligned situation, a distributed brain network was activated in the misaligned condition, including not only the dACC and SPG but also superior frontal gyrus and precuneus. These results suggest that SMS is related to a monitoring brain system, the scope of which varies according to the level of misalignment with social majority. The dorsolateral prefrontal cortex selectively interacted with SMS among the participants with a low switching threshold, indicating that its regulation on SMS may be sensitive to inter-individual variation. Our findings highlight the predominant roles of SMS and the prefrontal control system towards changes of mind under social influence.

Tropical cyclones (TCs) are extreme weather events that may result in enormous loss of life and property especially for countries surrounding the North Indian Ocean (NIO) rim. In this study, a regional scale spatial statistical model has been developed to define the relationship between TCs and sea surface temperature (SST)/tropical cyclone heat potential (TCHP) for the period 1979 to 2017 over the NIO region. The spatial model employed here tessellates the NIO basin with hexagonal grids (area of each hexagon is approximately 213,961 km2) in order to analyze the relationship between cyclone intensity and the two predictors-SST and TCHP. The role of SST and TCHP contribution to the NIO cyclone intensity is determined by using a geographically weighted regression (GWR) method. This study postulates that a hexagon with positive coefficient signifies a direct relationship between the cyclone intensity and the predictors, for example, between SST (TCHP) and the Bay of Bengal (Arabian Sea) TCs. Based on robust model verification and test of significance, it is attributed that the spatial model using GWR has the potential to model NIO cyclone intensity, particularly using SST as the predictor for Bay of Bengal and TCHP for the Arabian Sea.

The increase in frequency and duration of marine heatwaves (MHWs) under global warming brings great pressure to society. The high vulnerability of ecosystems to MHWs may lead to severe ecological and socioeconomic impacts. Most studies assessed future climate responses at the Paris Agreement temperature goals based on transient, rather than stabilization, model simulations. Here, we investigate the differences between transient and stabilization responses at global warming of 1.5 °C in terms of MHWs. Concentrations of greenhouse gases and response time scales to the anthropogenic forcing differ in these two types of simulations because subsurface ocean temperatures take decades to centuries to adjust under external forcing. While global mean metrics of MHWs show little difference between the transient and stabilization responses, significant regional disparities are revealed worldwide, including many climate change hotspots. Regionally intensified MHWs at stabilized 1.5 °C are mostly due to air-sea interactions and subsurface ocean warming that contributes to the stronger SST warming in eastern boundary upwelling systems and the southern Indian Ocean, indicative of potentially greater impacts on marine ecosystems in these regions. In contrast, MHWs would be alleviated in the central equatorial Pacific and Arctic in stabilization responses. Substantial differences in regional MHWs between the transient and stabilization responses oblige us to reconsider previous assessments regarding 1.5 °C warming and future mitigation pathways.

Anxious individuals tend to make pessimistic judgments in decision making under uncertainty. While this phenomenon is commonly attributed to risk aversion, loss aversion is a critical but often overlooked factor. In this study, we simultaneously examined risk aversion and loss aversion during decision making in high and low trait anxious individuals in a variable gain/loss gambling task during functional magnetic resonance imaging. Although high relative to low anxious individuals showed significant increased risk aversive behavior reflected by decreased overall gamble decisions, there was no group difference in subjective aversion to risk. Instead, loss aversion rather than risk aversion dominantly contributed to predict behavioral decisions, which was associated with attenuated functional connectivity between the amygdala-based emotional system and the prefrontal control regions. Our findings suggest a dominant role of loss aversion in maladaptive risk assessment of anxious individuals, underpinned by disorganization of emotion-related and cognitive-control-related brain networks.

Purpose: This study examined the correlation between social relational quality and hope among patients with permanent colostomies. Methods: Eighty-six eligible patients with permanent colostomies were recruited from a Class A tertiary hospital from July to December 2012. A self-designed demographic questionnaire, the Social Relational Quality Scale (SRQS), and the Herth Hope Index (HHI) were administered to all patients. Results: The total social relationship quality and hope scores were 49.42 ± 4.98 and 38.52 ± 4.64, respectively. The total scale score and composing subscale scores for social relationship quality and hope showed a statistically significant positive correlation with each other (r = 0.324–0.680; p

Nuclear transporter importin- β 1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin- β 1 inhibitor DD1 to afford an improved analog DD1 -Br with better tolerability (>25 folds) and oral bioavailability. DD1 -Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin- β 1, DD1 -Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin- β 1., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Chromatographic fractionation of the 95% EtOH extract of the roots of Stellera chamaejasme yielded 20 sesquiterpenoids of four different types, guaiane-, carotane-, sesquicarane-, and alpiniane-types. Among them, sesquistrachanoids A-F were previously undescribed ones, whose structures including absolute configurations were elucidated by spectroscopic methods, the Mo 2 (OAc) 4 -induced ECD experiment, and analysis of experimental and calculated 1D NMR and ECD data. Sesquistrachanoid A is a 2,3-seco-guaiane-type sesquiterpenoid with a α-pyrone core and sesquistrachanoid B is the first example of 8,9-seco-guaiane-type sesquiterpenoid featured with an 1,8-δ-lactone core. Sesquistrachanoid C is a guaiane sesquiterpenoid characterized by a peroxide bridge between C-8 and C-10. All sesquiterpenoids were evaluated for their neuroprotective effects on cell damage induced by sodium nitroprusside in PC-12 cells. The bioassay results showed that six compounds at 10 μM could restore the cell viability, being comparable to that of the positive control edaravone. The mechanistic study on the most pronounced activity compound, stelleraguaianone B, demonstrated that it played a neuroprotective role by promoting the mRNA expression of antioxidant enzymes to reduce oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sensitization of Cr(VI) oxyanions in environmentally or industrially relevant aquatic media is highly desired owning to their biological toxicity and essential role in nuclear fuel cycle. However, many chemosensors of CrO 4 2- and Cr 2 O 7 2- suffer from critical drawbacks, including insufficient sensitivity, selectivity, and/or hydrolytic stability. In this work, we prepared a hydrolytically stable metal-organic framework, namely Hf-BITD, which can retain its crystallinity and structural integrity in solutions over a wide pH range (0-12) and in 3 M HCl. The strong emission via rigidifying fluorescent linkers allows for sensing of CrO 4 2- and Cr 2 O 7 2- in a luminescence quenching manner, with excellent linear correlations (I 0 /I = 1+ K sv [Q]) in the ranges of 0-80 μM and 0-50 μM for CrO 4 2- and Cr 2 O 7 2- , respectively. The adsorption of Cr(VI) oxyanions and the concomitant resonance energy transfer between framework and analysts efficiently turn the emission of Hf-BITD off, which allows for selective recognition of CrO 4 2- and Cr 2 O 7 2- with detection limits of 0.38 nM and 0.33 nM, respectively. Furthermore, fabrication of Hf-BITD incorporating PVDF membrane makes Hf-BITD@PVDF a promising candidate for facile and effective sensitization of Cr(VI) oxyanions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tigliane and rhamnofolane diterpenoids bearing glycosyl substituents are rarely found in nature. In the current study, seven new tigliane glycosides, euphorwallsides A - G (1-7), and five new rhamnofolane glycosides, euphorwallsides H - L (8-12), were isolated from the whole plants of Euphorbia wallichii. Their structures were elucidated by a combination of spectroscopic, computational, and chemical means. The aglycones of 1-5 represent a rare class of 13-deoxygenated tiglianes, while those of 8-12 represent the first examples of 4-deoxygenated rhamnofolanes. 2, 3, 5, 7, 8, and 12 showed significant neuroprotective effects on sodium nitroprusside (SNP)-induced neuronal death in pheochromocytoma cell line PC-12 at 10 μM, being more active than the clinical drug, edaravone. Mechanistic study revealed that the most active compound, 3, could inhibit reactive oxygen species (ROS) accumulation and restore the mitochondrial membrane potential via modulating the Nrf2 signaling pathway in PC-12 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the γδ IEL compartment under homeostatic conditions has yet to be determined. We identified a novel γδ IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple Vγ subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal γδ IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in γδ IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with γδ IEL expansion. Using intravital microscopy, we find that hyperproliferative γδ IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate γδ IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Seven previously undescribed polycyclic diterpenoids, euphonoids A-G, including four ent-abietanes, two ent-atisanes, and one ent-kaurene, along with 26 known analogues were isolated from the roots of Euphorbia fischeriana. The structures of the undescribed compounds were elucidated by spectroscopic analysis, ECD calculations, and single crystal X-ray diffraction. Besides, the structure of a previously reported ent-abietane diterpenoid, fischeriabietane A, was revised. All the isolates were screened for the cytotoxicities against five cancer cell lines. Euphonoid A, fischeriabietane A, 11-oxo-ebracteolatanolide B, caudicifolin, jolkinolide B, and methyl-8,11-3-dihydroxy-12-oxo-ent-abietadi-13,15(17)-ene-16-oate showed significant inhibitory activities against human prostate cancer C4-2B and C4-2B/ENZR cell lines, with IC 50 values being less than 10 μM. The brief structure-activity relationships (SARs) of these diterpenoids were also discussed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As a kind of three-dimensional graphene architecture material with superhydrophobic, low density, high specific surface area and porosity, graphene aerogel (GA) can be used to immobilize extractant to constitute the solvent impregnated adsorbent. In this paper, the N,N,N',N'-tetraoctyldiglycolamide impregnated graphene aerogel ( GA-TODGA) was prepared to remove the thorium from aqueous solution. It is found that the adsorption of thorium on GA-TODGA is strongly dependent on the concentration of TODGA in GA and HNO 3 in aqueous solution. Compared with other solvent impregnated adsorbents, the adsorption capacity of GA-TODGA is much higher due to the high immobilization capacity of GA for TODGA. Furthermore, the GA-TODGA also possesses excellent stability and reusability, ensuring the application potential of using GA-TODGA in large scale., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Eight previously undescribed diterpenoids, crolaevinoids A-H, including two halimanes, four clerodanes, and two laevinanes, along with six known analogues were isolated from the twigs of Croton laevigatus. The structures of the previously undescribed were elucidated by spectroscopic analysis, and their absolute configurations were determined by combination of a single crystal X-ray diffraction and CD analysis (exciton chirality and Rh 2 (OCOCF 3 ) 4 -induced methods). Crolaevinoids A and B represent the first halimane diterpenoids with a unique lactone bridge between C-12 and C-17. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Furocrotinsulolide A and 3,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olide exhibited pronounced inhibition of NO production with IC 50 values of 10.4 ± 0.8 and 6.0 ± 1.0 μM, respectively, being more potent than the positive control, quercetin (IC 50  = 13.1 ± 1.9 μM)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A new approach for uranium extraction employing graphene aerogel (GA) as a skeleton loading organic solution (GA-LOS) is proposed and investigated. Firstly, the GA with super-hydrophobicity and high organic solution absorption capacity was fabricated by one-step reduction and self-assembly of graphene oxide with ethylenediamine. By adsorbing Tri-n-butyl phosphate (TBP)/n-dodecane solution to prepare GA-LOS, the extraction of U(VI) from nitric acid medium using GA-LOS was investigated and compared with conventional solvent extraction. It is found that the GA-LOS method can provide several advantages over conventional solvent extraction and adsorption due to the elimination of aqueous-organic mixing-separation procedures and easy solid-liquid separation. Furthermore, it also possesses higher extraction capacity (the saturated extraction capacity of GA loading TBP for U(VI) was 316.3mgg -1 ) and lower consumption of organic diluents, leading to less organic waste. Moreover, the stability of GA-LOS in aqueous solution and cycling test were also studied, and it shows a remarkable regeneration capability, making it an ideal candidate for metal extraction from aqueous solution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thelohanellus wuhanensis Xiao & Chen, 1993 infects allogynogenetic gibel carp Carassius auratus gibelio (Bloch) forming numerous plasmodia in the skin, resulting in high mortality of juvenile host fish. Within this paper we supplement the identification of this pathogenic species with information on its ultrastructural and histological characteristics. Measurements of the spores corresponded to the original description, but asymmetry in the spore shape was recorded. Scanning electron microscopy revealed that the spore surface was smooth and the sutural ridge of the anterior end was asymmetric as one side was thinner. In addition, the sutural line was either straight or "S" like. Transmission electron microscopy showed that most spores were surrounded by a membranous sheath, while some sheaths were difficult to observe under light microscopy as the closeness of the sheath to the valves. The small electron-dense granules in the sporoplasm ranged from 0.66 to 1.14 μm in diameter, but their function was unknown. Histology showed that the plasmodia of T. wuhanensis developed in the stratum spongiosum of skin dermis. The presence of melanocytes around the plasmodia was responsible for the black spots on T. wuhanensis cyst. The plasmodia were curved, perhaps to expand the surface area in contact with adjacent host tissue, facilitating the attainment of nutrients from the host., (Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.)

A novel dualmodality probe was prepared by linking (188)Re-HGRGD (D) F with CdTe QDs, which was monitored using radio-thin layer chromatography (TLC) and -high performance liquid chromatography (HPLC). The (188)Re-HGRGD (D) F-CdTe QDs probe possesses a radiochemistry yield of 92.1% and strong photoluminescence (PL) stability. However, the radiochemical purity of (188)Re-HGRGD (D) F-QDs would reduce to 74.8%, which should be further improved, after incubation with newborn calf serum (NCF) for 24h. Human glioblastoma U87MG cells, known to express a high-affinity to RGD, were used to assess the in vitro cell binding of probe. The results showed that the radio-signal was in accord with the change of PL intensity, which meant the successful integration of (188)Re and QDs., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)