Optical biomarker analysis for renal cell carcinoma obtained from preoperative and postoperative patients using ATR-FTIR spectroscopy.

Renal cell carcinoma (RCC) is the most common malignant tumor in the urinary system, accounting for 80 % to 90 % for all renal malignancies. Traditional diagnostic methods like magnetic resonance imaging (MRI) and computed tomography (CT) lack the sensitivity and specificity as they lack specific biomarkers. These limitations impede effective monitoring of tumor recurrence. This study aims to employ Attenuated Total Reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, an optical technology sensitive to molecular groups, to analyze the potential optical biomarkers in urine and plasma samples from RCC patients pre- and post-surgery. The results reveal distinctive spectral information from both plasma and urine samples. Post-surgery urine spectra exhibit complexity compared to plasma, showing reduced content at 1072 cm-1, 1347 cm-1 and 1654 cm-1 bands, while increased content at 1112 cm-1, 1143 cm-1, 1447 cm-1, 3334 cm-1 and 3420 cm-1 bands. Utilizing machine learning models such as eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), and artificial neural network (ANN), the study evaluated plasma and urine samples pre- and post-surgery. Remarkably, the XGBoost method excelled in distinguishing between tumor conditions and recovery, achieving an impressive AUC value of 0.99. These results underscore the potential of ATR-FTIR technology in identifying RCC optical biomarkers, with XGBoost showing promise as a valuable screening tool for RCC recurrence diagnosis.

Beliefs about social mobility in young American children.

Although actual experiences of upward social mobility are historically low, many adolescents and adults express a belief in social mobility (e.g., that social status can change). Although a belief in upward mobility (e.g., that status can improve) can be helpful for economically disadvantaged adolescents and adults, a belief in upward social mobility in adults is also associated with greater acceptance of societal inequality. While this belief might have similar benefits or consequences in children, no previous work has examined whether children are even capable of reasoning about social mobility. This is surprising, given that elementary-aged children exhibit sophisticated reasoning about both social status, as well as about the fixedness or malleability of properties and group membership. Across an economically advantaged group of 5- to 12-year-old American children (N = 151, Mage = 8.91, 63% racial majority, 25% racially marginalized; Mhousehold income = $133,064), we found evidence that children can reason about social mobility for their own families and for others. Similar to research in adults, children believe that others are more likely to experience upward than downward mobility. However, in contrast to adult's typical beliefs-but in line with economic realities-between 7- and 9-years-old, children become less likely to expect upward mobility for economically disadvantaged, versus advantaged, families. In sum, children are capable of reasoning about social mobility in nuanced ways; future work should explore the implications of these beliefs. RESEARCH HIGHLIGHTS: Despite harsh economic realities, a belief in upward social mobility and the American Dream is alive and well. Between 7 and 9 years of age, economically advantaged, American children begin to expect economically disadvantaged families to experience less upward mobility than economically advantaged families. Children's beliefs about social mobility better accord with reality than adults' do.

Correction: A Y1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer.

Correction for 'A Y1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer' by Yinjie Wang et al., Biomater. Sci., 2019, 7, 4748-4757, https://doi.org/10.1039/C9BM00337A.

The histone deacetylase SRT2 enhances the tolerance of chrysanthemum to low temperatures through the ROS scavenging system.

Low temperatures can severely affect plant growth and reduce their ornamental value. A family of plant histone deacetylases allows plants to cope with both biotic and abiotic stresses. In this study, we screened and cloned the cDNA of DgSRT2 obtained from transcriptome sequencing of chrysanthemum leaves under low-temperature stress. Sequence analysis showed that DgSRT2 belongs to the sirtuin family of histone deacetylases. We obtained the stable transgenic chrysanthemum lines OE-2 and OE-12. DgSRT2 showed tissue specificity in wild-type chrysanthemum and was most highly expressed in leaves. Under low-temperature stress, the OE lines showed higher survival rates, proline content, solute content, and antioxidant enzyme activities, and lower relative electrolyte leakage, malondialdehyde, hydrogen peroxide, and superoxide ion accumulation than the wild-type lines. This work suggests that DgSRT2 can serve as an essential gene for enhancing cold resistance in plants. In addition, a series of cold-responsive genes in the OE line were compared with WT. The results showed that DgSRT2 exerted a positive regulatory effect by up-regulating the transcript levels of cold-responsive genes. The above genes help to increase antioxidant activity, maintain membrane stability and improve osmoregulation, thereby enhancing survival under cold stress. It can be concluded from the above work that DgSRT2 enhances chrysanthemum tolerance to low temperatures by scavenging the ROS system.

Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom-economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

Analysis of Carotenoids and Gene Expression in Apple Germplasm Resources Reveals the Role of MdCRTISO and MdLCYE in the Accumulation of Carotenoids.

Carotenoids play an important role in the coloring and nutritional value of apple (Malus spp.) fruits. Here, six carotenoids, including lutein, zeaxanthin, ß-carotene, ß-cryptoxanthin, violaxanthin, and neoxanthin, were detected in 105 fruits of apple germplasm resources, which showed a skewed distribution in both the peel and pulp. There were more carotenoids in the peel than in the pulp, and lutein and ß-carotene were the primary carotenoids that were present. The expression levels of most carotenoid pathway genes in germplasm fruits during fruit development were higher in the fruits that had an abundance of carotenoids. A linear relationship analysis showed that the expression levels of MdCRTISO and MdLCYE were highly correlated with the content of carotenoids. The leaves accumulated the greatest number of carotenoids, while the roots had the lowest amount. MdCRTISO and MdLCYE were highly expressed in the fruits compared to other tissues. Transgenic calli and transiently transformed fruits confirmed that MdCRTISO and MdLCYE affected the biosynthesis of carotenoids owing to their effects on the expression of other genes for enzymes in the carotenoid pathway. Our findings will extend the understanding of carotenoid biosynthesis in apple and excavate apple germplasm resources with rich carotenoids to breed high-quality apples.

Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.

Diamond-based T1 relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.

Should leaders conform? Developmental evidence from the United States and China.

Leadership is inextricably embedded in human groups. One central obligation of leaders is to embody the identity of their group by acting in line with group norms. Yet little is known about how leadership and conformity are initially associated in people's minds, how this association develops in childhood, and how cultural values shape this association. The present research tested 4- to 11-year-olds in the United States and China to address these questions by comparing children's evaluations of a leader's versus an ordinary group member's nonconformity. In Experiments 1 and 3 (N = 114 and 116, respectively), children saw two novel groups engage in distinct behaviors (e.g., listening to different kinds of music). A leader or a nonleader acted against their respective group norms. Next, children provided evaluations of the nonconformity. In both populations, whereas younger children (4- to 7-year-olds) evaluated the leader's nonconformity more positively relative to the nonleader's, older children (10- to 11-year-olds) evaluated the leader's nonconformity more negatively. Notably, children in China developed more negative attitudes toward a leader's nonconformity than children in the United States. Experiment 2 (N = 66) ruled out the possibility that younger children's favorable evaluations of the leader's nonconformity stemmed from their general positivity toward leaders. Taken together, children in the two countries gradually conceptualize leaders as central group members and expect them to follow group norms. These findings contribute to theories on early leadership cognition and highlight the importance of taking a cross-cultural approach to understand its development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Do American children automatically encode cues to wealth?

As adults, we readily notice markers of social status and wealth and draw conclusions about individuals based on these cues. Do children do the same? Using a "Who Said What?" task across 5- to 9-year-old American children (n = 159; Mage = 7.44 years; 51.6% female, 47.2% male, 1.2% nonconforming or not provided; 59.1% White, 23.3% racial-ethnic minority, 17.6% not provided) and adults (n = 182; 84.1% female, 13.7% male, 2.2% nonconforming or not provided; 54.9% White, 44.5% racial-ethnic minority, 0.6% not provided), we found that both children and adults automatically encode (i.e., spontaneously notice and remember) occupational cues (i.e., work attire) and quantitative cues (i.e., amount of money) to wealth but that only adults automatically encode qualitative cues to wealth (i.e., car quality), suggesting developmental changes in which types of cues to wealth are most salient. Furthermore, automatic encoding in children was sensitive to contextual factors; children from communities with less affluence and higher rates of unemployment were more likely to encode some wealth cues than their peers from more affluent and employed communities. Finally, from 5 to 7 years of age, children began to draw connections between wealth cues, using occupational cues to make inferences about the quantity and quality of others' possessions. This research highlights the changing salience of wealth cues across development and suggests that even young children are likely to notice economic inequality and thus to be ready for conversations about inequality, as well as the origins of inequality, at an earlier age than previously supposed.

Lysine malonylation of DgnsLIPID TRANSFER PROTEIN1 at the K81 site improves cold resistance in chrysanthemum.

Lysine malonylation (Kmal) is a recently discovered posttranslational modification, and its role in the response to abiotic stress has not been reported in plants. In this study, we isolated a nonspecific lipid transfer protein, DgnsLTP1, from chrysanthemum (Dendranthema grandiflorum var. Jinba). Overexpression and CRISPR-Cas9-mediated gene editing of DgnsLTP1 demonstrated that the protein endows chrysanthemum with cold tolerance. Yeast 2-hybrid, bimolecular fluorescence complementation, luciferase complementation imaging, and coimmunoprecipitation experimental results showed that DgnsLTP1 interacts with a plasma membrane intrinsic protein (PIP) DgPIP. Overexpressing DgPIP boosted the expression of DgGPX (glutathione peroxidase), increased the activity of GPX, and decreased the accumulation of reactive oxygen species (ROS), thereby enhancing the low-temperature stress tolerance of chrysanthemum, while the CRISPR-Cas9-mediated mutant dgpip inhibited this process. Transgenic analyses in chrysanthemum showed that DgnsLTP1 improves the cold resistance of chrysanthemum in a DgPIP-dependent manner. Moreover, Kmal of DgnsLTP1 at the K81 site prevented the degradation of DgPIP in Nicotiana benthamiana and chrysanthemum, further promoted DgGPX expression, enhanced GPX activity, and scavenged excess ROS produced by cold stress, thereby further enhancing the cold resistance of chrysanthemum.

The immune checkpoint molecule, VTCN1/B7-H4, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived model of human trophoblast.

The placenta acts as a protective barrier to pathogens and other harmful substances present in the maternal circulation throughout pregnancy. Disruption of placental development can lead to complications of pregnancy such as preeclampsia, intrauterine growth retardation and preterm birth. In previous work, we have shown that expression of the immune checkpoint regulator, B7-H4/VTCN1, is increased upon differentiation of human embryonic stem cells (hESC) to an in vitro model of primitive trophoblast (TB), that VTCN1/B7-H4 is expressed in first trimester but not term human placenta and that primitive trophoblast may be uniquely susceptible to certain pathogens. Here we report on the role of VTCN1 in trophoblast lineage development and anti-viral responses and the effects of changes in these processes on major histocompatibility complex (MHC) class I expression and peripheral NK cell phenotypes.

Biological response of 3D-printedß-tricalcium phosphate bioceramic scaffolds with the hollow tube structure.

It is a large clinical challenge to repair critical-size bone defects, and vascularization in the early stage is of vital importance in bone regeneration. In recent years, 3D-printed bioceramic is a kind of common bioactive scaffold for repairing bone defects. However, conventional 3D-printed bioceramic scaffolds consist of stacked solid struts with low porosity, which limits the ability of angiogenesis and bone regeneration. The hollow tube structure can induce endothelial cells to build the vascular system. In this study,ß-tricalcium phosphate (ß-TCP) bioceramic scaffolds containing the hollow tube structure were prepared with digital light processing-based 3D printing strategy. The physicochemical properties and osteogenic activities of prepared scaffolds could be precisely controlled by adjusting the parameters of hollow tubes. Compared with solid bioceramic scaffolds, such scaffolds could significantly improve the proliferation and attachment activity of rabbit bone mesenchymal stem cellsin vitro, and facilitate early angiogenesis and subsequent osteogenesisin vivo. Therefore,ß-TCP bioceramic scaffolds with the hollow tube structure possess great potential application for the treatment of critical-size bone defects.

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma.

Recent studies have demonstrated the close relationship between parathyroid adenoma (PA) and thyroid follicular adenoma (FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3',5'-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was>0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression and the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.

Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles.

Chiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles.

Impacts of Cross-Sectoral Climate Policy on Forest Carbon Sinks and Their Spatial Spillover: Evidence from Chinese Provincial Panel Data.

This paper examines the impact of cross-sectoral climate policy on forest carbon sinks. Due to the complexity of the climate change issue and the professional division of labor among government departments, cross-sectoral cooperation in formulating climate policy is a desirable strategy. Forest carbon sinks play an important role in addressing climate change, but there are few studies focusing on forest carbon sinks and cross-sectoral climate policies. Thus, based on the panel data of 30 provinces and cities in China from 2007 to 2020, this paper establishes a benchmark regression model and a spatial panel model to analyze the impact of cross-sectoral climate policies on forest carbon sinks. We find that cross-sectoral climate policies positively impact forest carbon sinks. Under the influence of the "demonstration effect", we find that cross-sectoral climate policies have a positive impact not only on the forest carbon sinks in the region but also on those in the neighboring region. Further analysis shows that for provinces with less developed forestry industry and small forest areas, the positive effect of cross-sectoral climate policies on forest carbon sinks is more obvious. Overall, this paper can serve as an important reference for local governments to formulate climate policies and increase the capacity of forest carbon sinks.

Functionalized Fluorescent Nanodiamonds for Simultaneous Drug Delivery and Quantum Sensing in HeLa Cells.

Here, we present multifunctional fluorescent nanodiamonds (FNDs) for simultaneous drug delivery and free radical detection. For this purpose, we modified FNDs containing nitrogen vacancy (NV) centers with a diazoxide derivative. We found that our particles enter cells more easily and are able to deliver this cancer drug into HeLa cells. The particles were characterized by infrared spectroscopy, dynamic light scattering, and secondary electron microscopy. Compared to the free drug, we observe a sustained release over 72 h rather than 12 h for the free drug. Apart from releasing the drug, with these particles, we can measure the drug's effect on free radical generation directly. This has the advantage that the response is measured locally, where the drug is released. These FNDs change their optical properties based on their magnetic surrounding. More specifically, we make use of a technique called relaxometry to detect spin noise from the free radical at the nanoscale with subcellular resolution. We further compared the results from our new technique with a conventional fluorescence assay for the detection of reactive oxygen species. This provides a new method to investigate the relationship between drug release and the response by the cell via radical formation or inhibition.

DgbZIP3 interacts with DgbZIP2 to increase the expression of DgPOD for cold stress tolerance in chrysanthemum.

The bZIP transcription factor plays a very important role in abiotic stresses, e.g. drought, salt, and low-temperature stress, but the mechanism of action at low temperature is still unclear. In this study, overexpression of DgbZIP3 led to increased tolerance of chrysanthemum (Chrysanthemum morifolium Ramat.) to cold stress, whereas antisense suppression of DgbZIP3 resulted in decreased tolerance. Electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), luciferase complementary imaging analysis (LCI), and dual-luciferase reporter gene detection (DLA) experiments indicated that DgbZIP3 directly bound to the promoter of DgPOD and activated its expression. DgbZIP2 was identified as a DgbZIP3-interacting protein using yeast two-hybrid, co-immunoprecipitation, LCI, and bimolecular fluorescence complementation assays. Overexpression of DgbZIP2 led to increased tolerance of chrysanthemum to cold stress, whereas antisense suppression of DgbZIP2 resulted in decreased tolerance. A ChIP-qPCR experiment showed that DgbZIP2 was highly enriched in the promoter of DgPOD, while DLA, EMSA, and LCI experiments further showed that DgbZIP2 could not directly regulate the expression of DgPOD. The above results show that DgbZIP3 interacts with DgbZIP2 to regulate the expression of DgPOD to promote an increase in peroxidase activity, thereby regulating the balance of reactive oxygen species and improving the tolerance of chrysanthemum to low-temperature stress.

A natural antisense RNA improves chrysanthemum cold tolerance by regulating the transcription factor DgTCP1.

Long noncoding RNAs (lncRNAs) are widely involved in the regulation of plant growth and development, but their mechanism of action in response to cold stress in plants remains unclear. Here, we found an lncRNA transcribed from the antisense strand of DgTCP1 (class I Teosinte branched1/Cycloidea/Proliferating [TCP] transcription factor) of chrysanthemum (Chrysanthemum morifolium Ramat.), named DglncTCP1. During the response of chrysanthemum to cold stress, overexpression of DgTCP1 improved the cold tolerance of chrysanthemum, while the DgTCP1 editing line (dgtcp1) showed decreased tolerance to cold stress. Overexpression of DglncTCP1 also increased the cold tolerance of chrysanthemum, while the DglncTCP1 amiRNA lines (DglncTCP1 amiR-18/38) also showed decreased tolerance to cold stress. Additionally, the overexpression of DglncTCP1 upregulated the expression of DgTCP1. This indicated that DglncTCP1 may play a cis-regulatory role in the regulatory process of DgTCP1 in cold tolerance. DglncTCP1 acts as a scaffold to recruit the histone modification protein DgATX (ARABIDOPSIS TRITHORAX from chrysanthemum) to DgTCP1 to enhance H3K4me3 levels, thereby activating DgTCP1 expression. Moreover, DgTCP1 can directly target DgPOD (peroxidase gene from chrysanthemum) to promote its expression and reduce reactive oxygen species accumulation, thereby improving the cold tolerance of chrysanthemum. In conclusion, these results suggest that natural antisense lncRNA plays a key role in improving the cold tolerance of chrysanthemum.

Modification effects of seasonal and temperature variation on the association between exposure to nitrogen dioxide and ischemic stroke onset in Shenzhen, China.

The independent associations of extreme temperature and ambient air pollutant with the admission to hospital and mortality of ischemic stroke have been widely investigated. However, knowledge about the modification effects of variation in season and temperature on the association between exposure to nitrogen dioxide (NO2) and ischemic stroke onset is still limited. This study purposed to explore the effect of NO2 on daily ischemic stroke onset modified by season and ambient temperature, and identify the potential population that susceptible to ischemic stroke onset connected with NO2 and ambient temperature. Data on daily ischemic stroke counts, weather conditions, and ambient air pollutant concentrations in Shenzhen were collected between January 1, 2008, and December 31, 2014. The seasonal effect on the NO2-associated onset was measured by a distributed-lag linear model. Furthermore, a generalized additive model that incorporated with stratification analyses was used to calculate the interactive effects between NO2 and ambient temperature. During the winter, the average percentage increase in daily ischemic stroke onset for each 10 µg/m3 increment in NO2 concentration on lagged 2 days was 3.05% (95% CI: 1.31-4.82%), while there was no statistically significant effect of NO2 during summer. And the low-temperature days ([Formula: see text] mean temperature), with a 2.23% increase in incidence (95% CI: 1.18-3.29%) for the same concentration increase in NO2, were significant higher than high temperature days ([Formula: see text] mean temperature). The modification effects of temperature on the study association were more pronounced in individuals aged 65 years or more and in males. The adverse health effects of NO2 on ischemic stroke are more pronounced during winter or low temperature periods. Elderly adults or males presented higher risks with these exposures.