Comparative analysis of phenolic compounds in different thinned unripe kiwifruits and their biological functions.

Thinned unripe kiwifruits (TUK) are considered the major agro by-products in kiwifruit production. To promote their potential applications, polyphenols and biological effects of unripe fruits from nine commercial kiwifruit cultivars were compared. Our findings showed that TUK were rich in bioactive polyphenols, which varied greatly by different cultivars. Indeed, catechin, epicatechin, procyanidin PB1, procyanidin B2, protocatechuic acid, neochlorogenic acid, and gallic acid were measured as the major phenolic components in most TUK, with the highest levels observed in 'Hongao' and 'Cuiyu' cultivars. Furthermore, TUK exerted strong in vitro antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory activities. Particularly, their stronger antioxidant effects and inhibitory effects on digestive enzymes were probably attributed to their higher contents of phenolic compounds, especially procyanidin B2. Collectively, our findings reveal that TUK are potential resources of valuable polyphenols, which can be exploited as natural antioxidants and natural inhibitors of α-glucosidase and α-amylase.

HDAC6 mediates tumorigenesis during mitosis and the development of targeted deactivating agents.

Epigenetics, particularly deacetylation, plays a critical role in tumorigenesis as many carcinogens are under tight control by post-translational modification. HDAC6, an important and special histone deacetylase (HDAC) family member, has been indicated to increase carcinogenesis through various functions. Recent studies demonstrated the effects of HDAC6 inhibitors in mitotic arrest, however, detailed mechanisms still remain unknown. Herein, we review and summarize HDAC6-associated proteins that have been implicated in important roles in mitosis. We also discuss the development of medicinal agents targeting HDAC6.

Flexibility of parental-like or maternal-like gene expression under diverse environments contributes to combined drought avoidance and drought tolerance in a water-saving and drought-resistance rice hybrid.

KEY MESSAGE: The hybrid rice variety (Hanyou73) exhibits the maternal-like (HH7A) gene expression in roots and parental-like (HH3) gene expression in leaves to obtain both advantages of drought avoidance and drought tolerance from its two parents. BACKGROUND: Rice is one of the most important crops in the world. Rice production consumes lots of water and significantly suffers from the water deficiency and drought stress. The water-saving and drought-resistance rice (WDR) confers good drought resistance and performs well in the water-saving cultivation. MAIN FINDINGS: A hybrid WDR variety Hanyou73 (HY73) exhibited superior drought resistance compared with its parents Hanhui3 (HH3) and Huhan7A (HH7A). Studies on drought resistance related traits revealed that HY73 performed like HH3 and HH7A on drought tolerance and drought avoidance, respectively. Transcriptomes were analyzed for samples with various phytohormone treatments and abiotic stresses, in which HY73 was closer to HH3 in leaf samples while HH7A in root samples. HY73 and its parents differed largely in DEGs and GO analysis for DEGs suggested the different pathways of drought response in HH3 and HH7A. Parent-like expression analysis revealed that the higher-parent-like expression pattern was prevailing in HY73. In addition, patterns of the parent-like expression significantly transformed between abiotic-stressed/phytohormone-treated and control samples, which might help HY73 to adapt to different environments. WGCNA analysis for those parent-like expression genes revealed some drought resistant genes that should contribute to the superior drought resistance of HY73. Genetic variation on the promotor sequence was confirmed as the reason for the flexible parent-like gene expression in HY73. CONCLUSION: Our study uncovered the important roles of complementation of beneficial traits from parents and flexible gene expressions in drought resistance of HY73, which could facilitate the development of new WDR varieties.

Image quality and detection efficacy of zero echo time magnetic resonance imaging on Lung-RADS 2 pulmonary ground-glass nodules in comparison to thin-slice fat-saturated T2-weighted imaging.

Background: Widely used computed tomography (CT) screening increases the detection of pulmonary pure ground-glass nodules (pGGNs), often classified as the second category of Lung Imaging Reporting and Data System (Lung-RADS 2). Despite their low malignancy risk, these nodules pose significant challenges and necessitate accurate assessment to minimize the risk of long-term follow-ups. This study investigated the detection efficacy of zero echo time (ZTE) magnetic resonance imaging (MRI) and thin-slice fat-saturated T2-weighted imaging (T2WI-FS) on 3.0 T MRI on the predictive accuracy of invasiveness for Lung-RADS 2 pGGNs. Methods: This prospective study enrolled 83 consecutive patients with 110 pGGNs who underwent preoperative CT and MRI scans. All CT images were assessed by artificial intelligence (AI) software and confirmed by a thoracic radiologist. Another two radiologists blind to pathology results assessed MRI for image quality (objective and subjective evaluations) and detection of pGGNs. Differences in nodule diameter, CT density and detection rate were compared within different pathological groups. The objective and subjective image quality scores were compared using the Wilcoxon signed rank test between ZTE and T2WI-FS. Interobserver agreement was calculated using the kappa coefficient. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic accuracy for distinguishing invasiveness. Results: Among the 110 pGGNs evaluated, T2WI-FS demonstrated a higher detection rate (80.0%) compared to ZTE (51.8%). ZTE showed a superior signal-to-noise ratio (SNR) in the lung parenchyma, aorta, and peripheral lung structures, whereas T2WI-FS more effectively delineated tracheal walls and pulmonary nodules. Both observers rated ZTE higher for vascular and bronchial visibility, while T2WI-FS was better in terms of lower noise and fewer artifacts. Notably, ZTE visibility varied with pathological results, exhibiting a range from 0% in atypical adenomatous hyperplasia (AAH) to 94.1% in invasive adenocarcinoma (IAC). The key indicators for distinguishing invasive pGGNs from non-invasive ones were nodule diameter [area under the curve (AUC) =0.874], ZTE visibility (AUC =0.740), followed by CT values (AUC =0.682) and T2WI-FS visibility (AUC =0.678). Conclusions: MRI has the potential to detect and predict the invasiveness of pGGN. Both T2WI-FS and ZTE demonstrate reliable image quality in pulmonary imaging, each displaying strengths in visualizing pGGN. Thin-slice T2WI-FS has a superior detection rate, while ZTE better predicts histological invasiveness.

Highly sensitive ECL detection of miRNA based on self-generated coreactant and target-induced catalyzed hairpin assembly.

BACKGROUND: Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests. RESULTS: Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H2O2), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H2O2, and then H2O2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O2-•. As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch. SIGNIFICANCE: Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application.

Metal(loid) uptake and physiological response of Coix lacryma-jobi L. to soil potentially toxic elements in a polluted metal-mining area.

Coix lacryma-jobi L. is a traditional medicinal plant in east Asia and is an important crop in Guizhou province, southwest China, where there are elevated levels of soil mercury and arsenic (As). Exposure to multiple potentially toxic elements (PTEs) may affect plant accumulation of metal(loid)s and food safety in regions with high geological metal concentrations. Field experiments were conducted to study the effects of PTEs on metal(loid) accumulation and physiological response of C. lacryma in different plant parts at three pollution levels. Total root length, number of root tips, number of branches, and number of root crosses increased with increasing pollution level, with increases in highly polluted areas of 44.2, 57.0, 79.6, and 97.2%, respectively, compared to lightly polluted areas. Under multi-element stress the activity of C. lacryma antioxidant oxidase showed an increase at low and medium PTE concentrations and inhibition at high concentrations. The As contents were all below the maximum limit of cereal food contaminants in China (GB 2762-2022, As < 0.5 mg kg-1). The stems had high Tl bioconcentration factors but the translocation factors from stem to grain were very low, indicating that the stems may be a key plant part restricting Tl transport to the grains. C. lacryma increased root retention and reduced the transport effect, thus reducing metal accumulation in the grains. C. lacryma adapted to PTE stress through root remodeling and enhanced antioxidant enzyme activities.

Identifying the critical windows of temperature extremes exposure and congenital heart diseases.

The associations between atmospheric temperature and congenital heart disease (CHD) and its subtypes are still inconclusive. In this population-based retrospective case-control study, 643 CHD cases and 3,215 non-CHD controls were analyzed through distributed lag nonlinear model to estimate the effect of weekly temperature exposure on CHD risk and to identify potentially vulnerable windows. Through the binary logistic regression model, we found that elevated temperature in the first trimester was associated with an increased risk of overall CHD and ventricular septal defect (VSD) (OR: 1.059, 95% CI: 1.002-1.119; OR: 1.094, 95% CI: 1.005-1.190, respectively), while increased temperature in the second trimester was significantly positively correlated with atrial septal defect (ASD) risk. However, the results of the DLNM showed a nonlinear relationship between the weekly average temperature and the risk of total CHDs and the subtypes. Exposure to extremely, moderately, and mildly high temperatures significantly increased the risk of overall CHD, ASD and VSD, and the critical windows were mainly concentrated at the 5th-11th and 23rd-27th weeks of gestation. Low-temperature extreme exposure resulted in vulnerable windows for ASD only: 13th-14th gestational weeks. No significant positive associations were found between extreme temperature and patent ductus arteriosus or tetralogy of Fallot. In the current context of climate change, our results add new evidence to the present understanding of the effects of high- and low-temperature extreme exposure on CHD and its main subtypes.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Improving the lesion appearance on FLAIR images synthetized from quantitative MRI: a fast, hybrid approach.

OBJECTIVE: The image quality of synthetized FLAIR (fluid attenuated inversion recovery) images is generally inferior to its conventional counterpart, especially regarding the lesion contrast mismatch. This work aimed to improve the lesion appearance through a hybrid methodology. MATERIALS AND METHODS: We combined a full brain 5-min MR-STAT acquisition followed by FLAIR synthetization step with an ultra-under sampled conventional FLAIR sequence and performed the retrospective and prospective analysis of the proposed method on the patient datasets and a healthy volunteer. RESULTS: All performance metrics of the proposed hybrid FLAIR images on patient datasets were significantly higher than those of the physics-based FLAIR images (p < 0.005), and comparable to those of conventional FLAIR images. The small difference between prospective and retrospective analysis on a healthy volunteer demonstrated the validity of the retrospective analysis of the hybrid method as presented for the patient datasets. DISCUSSION: The proposed hybrid FLAIR achieved an improved lesion appearance in the clinical cases with neurological diseases compared to the physics-based FLAIR images, Future prospective work on patient data will address the validation of the method from a diagnostic perspective by radiological inspection of the new images over a larger patient cohort.

Less is Better than More: Anthropomorphic App Icons With Small versus Large Tilt Angles Were Perceived as More Vivid.

In this study, we explored the impact of tilted designs of anthropomorphic app icons on users' perceptions of icon vividness across three experiments. In Experiment 1, tilting with an angle of 45° to the left increased perceived icon vividness. In Experiment 2, sequential icon tilt angles at 30° intervals manipulation showed that small tilt angles (e.g., 30° to the left or right) enhanced participant perceptions of dynamism and vividness, and participants perceived greater vividness in anthropomorphic app icons with slight tilting, driven by this increased dynamism. In Experiment 3, we excluded the effect of the completeness of icons on these participants' evaluations and affirmed that slightly tilting designs was an effective visual strategy for improving perceived vividness to attract users.

Optimizing Soil Sampling for Accurately Prediction of the Potential Remediation-Effective Area in a Contaminated Agricultural Land.

To achieve food security in a contaminated agricultural land, the remediation areas usually need more samples to obtain accurate contamination information and implement appropriate measures. In this study, we propose an optimal encryption sampling design to instead of the detailed survey, which is determined by the variation of heavy metals and the technology capability of remediation, to guide soil sampling for accurately remediation in the potential remediation-effective areas (PRA). The coefficient of screening variation threshold (CSVT), considering spatial variation, technology capacity and acceptable error of sampling, together with the spatial cyclic statistics method of neighbourhood analysis, is introduced to identify and delineate the PRA. Both of the hypothetical analysis and application case studies are conducted to illustrate the advantages and disadvantages of the optimization. The results show that, compared with the detailed survey, the optimal design shows a lower overall accuracy due to its sparsely sampling at the clean area, but it exhibits a similar effect of accurately prediction in boundary delineation and further classification in the PRA in both simulation and application studies. This work provides an effective method for subsequent accurate remediation at the investigation stage and valuable insights into application combination of technology capacity and contaminated agricultural land investigation.

First Report of Leaf Spot Caused by Alternaria alternata on Chard (Beta vulgaris var. cicla L.) in China.

Chard (Beta vulgaris var. cicla L.) is popular vegetable in China. In June 2023, a leaf spot disease was observed on Chard plants in Hunan Province (27°46'10.99″N, 112°05'52.80″E), China. The disease incidence was 30% in a surveyed of about 500 plants. Symptoms began as many light brown round- to polygon-shaped spots on chard leaves, then developed and enlarged into grayish-white lesions, with the edge of the spots brown to dark brown. A total of 10 symptomatic samples were randomly collected. To identify the pathogen, symptomatic tissues (0.5 × 0.5 cm) from the lesion margin surface were sterilized with 75% ethanol for 30 s and 2% NaClO for 1 min, rinsed 3 times with sterile water, air dried. The sterile pieces were placed on potato dextrose agar (PDA) and incubated at 25°C. A total of nine isolates were obtained. Fungal colonies cultured on potato carrot agar (PCA) were almost the same as each other, and two representative isolates (TC0, TC10) were used for further identification. On PCA, the fungal hyphae were initially white and finally gray-brown with flocculent aerial mycelia. Conidia were solitary or in chains, with various shapes, mostly subglobose, the size was 13.2 to 28.0 µm long and 5.8 to 13.0 µm wide (n = 30). The cultural and morphological characteristics of isolates were similar to those of Alternaria sp (Simmons et al. 2007). For molecular identification, four loci, ITS (White et al. 1990), RPB2 (O'Donnell, 2022), H3 (Zheng et al. 2015), and GAPDH (Berbee et al. 1999), were sequenced from two representative isolates (TC0, TC10). Compared with a reference isolate, Alternaria alternata strain CBS 107.27, GenBank accession nos. KP124300.1 (ITS), KP124768.1 (RPB2), KP124157.1 (GAPDH). The ITS, RPB2, and GAPDH sequences of TC0 and TC10 showed 99% (502 of 504 bp ), 100% (753 of 753 bp), and 99% (560 of 561 bp) similarity, respectively. Compared with a reference isolate, A. alternata isolate 21-5, GenBank accession no. MN840996.1 (H3), H3 sequences of TC0 and TC10 showed 99% (399 of 401 bp) similarity. The sequences of two isolates (TC0, TC10) were deposited in GenBank with accession numbers PP837733.1, PP565404.1(ITS), PP839298.1, PP573905.1(RPB2), PP839299.1, PP573904.1 (GAPDH), and PP839297.1, PP573903.1(H3). Phylogenetic trees were constructed using the sequences and showed that isolates (TC0, TC10) were in the same clade with A. alternata strains. TC0 and TC10 were identified as A. alternata based on the morphological characteristics and molecular phylogeny. Pathogenicity testing was conducted on six-month-old healthy plants, (cv. Green Stalk), three plants were inoculated by spraying spore solution (1 × 106 conidia/mL), and three plants were sprayed with sterile water as a control. The pathogenicity test was performed 3 times. Plants were maintained at 28°C and >80% RH. Plants showed symptoms after 30 days, symptoms were observed similar to those of the original infected plants, control plants were asymptomatic. The fungus was reisolated, confirmed as A. alternata based on conidial characteristics, no pathogenic fungus was isolated from the control plants. A. alternata has previously been reported on beet (also Beta vulgaris) in China (Tai, F. L. 1979; Zhuang, W. Y. 2005). To our knowledge, this is the first report of leaf spot caused by A. alternata on chard in China. This result may expand the etiological study of A. alternata and the control strategy of Chard leaf spot.

Binding Mechanism of Nitro Musks to Human Lactoferrin: Multispectral Approach, Docking and Molecular Dynamics Simulation.

Nitro musks are highly bioaccumulative and potentially carcinogenic, commonly used as additives in fabric softeners, detergents, and other household products. Furthermore, these substances have been detected in breast milk and human adipose tissue, posing a risk of direct exposure to pregnant women and infants. Human lactoferrin (HLF) is abundant in colostrum, and plays an important role in the non-specific immune system of the human body. In this study, the mechanisms of action of two nitro musk compounds, typical examples of synthetic musks, with HLF were investigated using molecular docking, dynamics simulation and multispectral methods. The fluorescence findings demonstrated that nitro musks quenched the intrinsic fluorescence of human lactoferrin through static quenching. Thermodynamic analysis of the binding parameters suggested that hydrophobic interactions acted synergistically in the formation of the complex. Moreover, analyses utilizing multispectral techniques, such as Fourier transform infrared (FTIR) spectroscopy, validated that the microenvironment and structure of HLF were altered in the presence of nitro musks. Finally, molecular docking and molecular dynamics simulations were employed to explore the specific binding mode of nitro musks with HLF and to assess the stability of the complex. These findings may provide a reference for assessing health risks to pregnant women and infants.

Cobalt exposure and pulmonary function reduction in chronic obstructive pulmonary disease patients: the mediating role of club cell secretory protein.

BACKGROUND: Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). METHODS: All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. RESULTS: Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. CONCLUSION: Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Asymmetrical Modification of Cyclopentadienyl Cobalt in Eu-MOF for C2H2/CO2 Separation.

The development of novel adsorption materials is of significance for the efficient and low-energy purification of acetylene (C2H2). Emerging metal-organic framework (MOF) adsorbents demonstrate great application prospects in the field of gas adsorption and separation. Herein, we synthesized a Eu-MOF asymmetrically modified with cyclopentadienyl cobalt exhibiting two different types of cages, denoted as UPC-119. Adsorption isotherms and dynamic breakthrough curves confirm its potential in C2H2/CO2 separation, which is further evidenced by theoretical simulations. The high adsorption capacity and low adsorption enthalpy render UPC-119 as a promising adsorbent for C2H2/CO2 separation with ease of regeneration.

Design, synthesis and biological evaluation of thieno[3,2-c]pyrazol-urea derivatives as potent glycogen synthase kinase 3ß inhibitors based on the DFG-out conformation.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential therapeutic target for the treatment of a variety of human diseases. Here, we report the design and synthesis of a series of thieno[3,2-c]pyrazol-urea derivatives and evaluation of their GSK-3ß inhibitory activity. Among these analogues, the compound without substitution on terminal phenyl ring (3a) was found to be the most potent GSK-3ß inhibitor with an IC50 of 74.4 nM, while substitution on the terminal phenyl (3b-3p) led to decreased potency, independent of the position, size, or electronic properties of the substituents. Kinase selectivity assay revealed that 3a showed good selectivity over a panel of kinases, but was less selective over CDK1, CDK2 and CDK5. Additionally, the pharmacological properties of the synthesized compounds were investigated computationally by the SwissADME and the results showed that most of the compounds have good ADME profiles.

Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women.

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.

Impact of Genetic Ancestry on T-cell Acute Lymphoblastic Leukemia Outcomes.

The influence of genetic ancestry on biology, survival outcomes, and risk stratification in T-cell Acute Lymphoblastic Leukemia (T-ALL) has not been explored. Genetic ancestry was genomically-derived from DNA-based single nucleotide polymorphisms in children and young adults with T-ALL treated on Children's Oncology Group trial AALL0434. We determined associations of genetic ancestry, leukemia genomics and survival outcomes; co-primary outcomes were genomic subtype, pathway alteration, overall survival (OS), and event-free survival (EFS). Among 1309 patients, T-ALL molecular subtypes varied significantly by genetic ancestry, including increased frequency of genomically defined ETP-like, MLLT10, and BCL11B-activated subtypes in patients of African ancestry. In multivariable Cox models adjusting for high-risk subtype and pathways, patients of Admixed American ancestry had superior 5-year EFS/OS compared with European; EFS/OS for patients of African and European ancestry were similar. The prognostic value of five commonly altered T-ALL genes varied by ancestry - including NOTCH1 , which was associated with superior OS for patients of European and Admixed American ancestry but non-prognostic among patients of African ancestry. Furthermore, a published five-gene risk classifier accurately risk stratified patients of European ancestry, but misclassified patients of African ancestry. We developed a penalized Cox model which successfully risk stratified patients across ancestries. Overall, 80% of patients had a genomic alteration in at least one gene with differential prognostic impact by genetic ancestry. T-ALL genomics and prognostic associations of genomic alterations vary by genetic ancestry. These data demonstrate the importance of incorporating genetic ancestry into analyses of tumor biology for risk classification algorithms.

Superiority of opioid free anesthesia with regional block over opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery: a randomized controlled trial.

BACKGROUND: Opioids are the main analgesic drugs used in the perioperative period, but they often have various adverse effects. Recent studies have shown that quadratus lumborum block (QLB) has an opioid sparing effect. The aim of this study was to further evaluate the effect of opioid-free anesthesia (OFA) combined with regional block on the quality of recovery in patients undergoing retroperitoneoscopic renal surgery. METHODS: Sixty patients undergoing elective retroperitoneoscopic renal surgery were divided into the opioid-free anesthesia with quadratus lumborum block group (OFA group, N.=30) and opioid anesthesia with quadratus lumborum block group (OA group, N.=30) using the random number table method. The main outcome measures were the quality of recovery assessed by Quality of Recover-40 (QoR-40) at the 24th postoperative hour. Secondary outcomes were postoperative pain score, postoperative opioid consumption, postoperative nausea and vomiting, time to ambulate, and time to readiness for discharge. RESULTS: The QoR-40 score on the first postoperative day was significantly higher in the OFA group than that in the OA group (175.41±6.74 vs. 165.07±4.55; P<0.05). OFA also significantly reduced postoperative pain (P<0.05) and morphine consumption at both the 24th and 48th postoperative hour (P<0.05), as well as time to ambulate, and time to readiness for discharge (P<0.05). CONCLUSIONS: OFA with regional block is superior to opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery.

Protocol for systematic review and meta-analysis on the efficacy and safety of acupuncture for residual low back pain after percutaneous kyphoplasty in patients with osteoporotic vertebral compression fracture.

INTRODUCTION: Osteoporotic vertebral compression fracture (OVCF) is a common complication in elderly patients with osteoporosis. Despite undergoing percutaneous kyphoplasty (PKP) treatment, a significant percentage of OVCF patients (1.8% to 31.9%) continue to experience residual low back pain. While acupuncture has shown promise in relieving this pain, there is currently no systematic review on its efficacy specifically for residual low back pain after PKP in OVCF patients. This project aims to evaluate the effectiveness and safety of acupuncture as a treatment for this condition. METHODS AND ANALYSIS: A comprehensive search will be conducted, including manual and electronic searches of literature published. Various databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wan-fang Database will be explored. Additional sources like bibliographies and meeting minutes will also be searched. All randomised controlled clinical trials related to acupuncture for treating residual low back pain after PKP in OVCF patients will be included. Two researchers will independently perform study selection, data extraction and quality assessment. The primary outcome measure will be pain relief assessed using a visual analogue scale (VAS) or other validated scales. Secondary outcomes include effectiveness, Oswestry dysfunction index (ODI), quality of life questionnaire (QUALEFFO-41), follow-up relapse rate and adverse events. If feasible, a meta-analysis using RevMan V.5.3 software will be conducted. Otherwise, descriptive or subgroup analyses will be performed. Database searches will commence after the publication of this agreement, with an estimated commencement date of 1 August 2024. ETHICS AND DISSEMINATION: Ethical approval is not required since this review does not involve individual patient data. The findings will be disseminated through peer-reviewed journals or relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023478838.