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SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

A half-metallic full-Heusler Mn2VAl alloy is a potential p-type thermoelectric material that can directly generate electricity from waste heat via the Seebeck effect. For practical use, the Seebeck coefficient S of Mn2VAl should be increased while maintaining a high electrical conductivity σ from its half-metallic character. Herein, we achieved this objective through antisite defect engineering. Theoretically, it was predicted that the S was maximized by regulating partial density of states of majority-spin sp-electrons through the control of the fraction of antisite defect, fAD, between V and Al atoms in Mn2VAl. Experimentally, a significant increase in S and a slight decrease in σ were observed for an Mn2VAl sample with an optimal fAD = 33%, enhancing the thermoelectric power factor PF by 2.7 times from an Mn2VAl sample with fAD = 14%. Furthermore, we combined the antisite defect engineering with a partial substitution method. An Mn2V(Al0.96Si0.04) sample with fAD = 33% exhibited the highest PF = 4.5 × 10−4 W·m−1·K−2 at 767 K among the samples. The maximum dimensionless figure-of-merit zT of the Mn2V(Al0.96Si0.04) sample with fAD = 33% was measured to be 3.4 × 10−2 at 767 K, which is the highest among the p-type half-metallic full-Heusler alloys.

This paper presents an experimental study on the compressive properties and creep behavior of Mg-Gd-Y-Zn-Mn-Nd alloy. A total of 42 specimens are prepared and tested, including 18 compression tests and 24 creep tests. The investigation aims to evaluate the influence of material orientation, temperature, and initial stress (for creep test only) on the compressive behavior of the Mg-Gd-Y-Zn-Mn-Nd alloy. First, the results of compression tests are analyzed, revealing insights into the anisotropic behavior, failure mode, yield strength, ultimate compressive strength, and failure strain of the Mg-Gd-Y-Zn-Mn-Nd alloy under compressive loading. Then, according to the experimental data from creep tests, where the steady creep rate, stress exponent and activation energy are calibrated. Furthermore, the creep mechanisms of the Mg-Gd-Y-Zn-Mn-Nd alloy under various material orientations are discussed. Additionally, the authors analyze and compare the Electron Backscatter Diffraction (EBSD) data of the Mg-Gd-Y-Zn-Mn-Nd alloy before and after undergoing compressive creep. Finally, based on the test results, a mathematical model is proposed to describe the development of compressive creep strain.

Objective This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice. Method Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD, n = 8), high-fat diet group (HFD, n = 8), and HFD+semaglutide group (Sema, n = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice. Result Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, Clostridia_UCG_014 and increased Romboutsia, Dubosiella, Enterorhabdus. Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. Romboutsia was positively correlated with TNFα, IL-6 and IL-1β. While Clostridia_UCG_014 was negatively related to TNFα, IL-6 and IL-1β. Conclusions For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.

Background High levels of catecholamines are cardiotoxic and associated with stress‐induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Methods and Results Purpose‐bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine‐stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High‐dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular‐aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800‐fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular‐aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Conclusions Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion‐induced ischemia. However, epinephrine itself has potentially harmful long‐lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Background Septic shock is associated with increases in end‐diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. Methods and Results Purpose‐bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular‐arterial coupling, and circumferential strain. Early during sepsis, (0–24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. Conclusions The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process of cell injury through ferroptosis, has the potential to ameliorate cell damage. In this study, we aimed to investigate the potential of berberine (BBR) as an inhibitor of ACSL4 in order to suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created in ApoE-/- mice by feeding a high fat diet for 16 weeks. Additionally, a mouse model with endothelium-specific overexpression of ACSL4 was established. BBR was administered orally to assess its potential therapeutic effects on atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low density lipoprotein (ox-LDL) to simulate atherosclerotic endothelial damage in vitro. The interaction between ACSL4 and BBR has been confirmed, with BBR playing a role in inhibiting erastin-induced ferroptosis by regulating ACSL4. Additionally, BBR has been found to inhibit lipid deposition, plaque formation, and collagen deposition in the aorta, thereby delaying the progression of atherosclerosis. It also restored the abnormal expression of ferroptosis-related proteins in atherosclerotic vascular endothelial cells both in vivo and in vitro. In conclusion, BBR, acting as an ACSL4 inhibitor, can improve atherosclerosis by inhibiting ferroptosis in endothelial cells. This highlights the potential of targeted inhibition of vascular endothelial ACSL4 as a strategy for treating atherosclerosis, with BBR being a candidate for this purpose.

Ultrasound imaging has a history of several decades. With its non-invasive, low-cost advantages, this technology has been widely used in medicine and there have been many significant breakthroughs in ultrasound imaging. Even so, there are still some drawbacks. Therefore, some novel image reconstruction and image analysis algorithms have been proposed to solve these problems. Although these new solutions have some effects, many of them introduce some other side effects, such as high computational complexity in beamforming. At the same time, the usage requirements of medical ultrasound equipment are relatively high, and it is not very user-friendly for inexperienced beginners. As artificial intelligence technology advances, some researchers have initiated efforts to deploy deep learning to address challenges in ultrasound imaging, such as reducing computational complexity in adaptive beamforming and aiding novices in image acquisition. In this survey, we are about to explore the application of deep learning in medical ultrasound imaging, spanning from image reconstruction to clinical diagnosis.

AimsPrimary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing’s syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD.MethodsDatabases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles.ResultsA total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations (PRKAR1A, PDE11A, PRKACA, CTNNB1, PDE8B, and ARMC5) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD (p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period.ConclusionsFor young patients with Cushing’s syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023416988.

Abstract Background Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non‐Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. Methods The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP‐5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. Results Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non‐Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, p .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, p

Abstract Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride‐based alloys are still the best for near‐room‐temperature applications. In this work, a ≈38% enhancement of the average ZT (300−473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2−yTe3‐based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6‐based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high‐density dislocations in the same region can effectively scatter the phonons, decoupling the electron‐phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single‐leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate‐matrix interface microstructure in improving the performance of materials for relatively low‐temperature applications.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p

Muscle is the main edible part of bony fish. The purpose of this study was to investigate the influences of phenylalanine (Phe) on muscle quality, amino acid composition, fatty acid composition, glucose metabolism, and protein deposition in adult grass carp. The diets at 2.30, 4.63, 7.51, 10.97, 13.53, and 17.07 g/kg Phe levels were fed for 9 weeks. The results manifested that Phe (10.97–13.53 g/kg) increased the pH of the fillets and decreased muscle cooking loss and lactic acid content; Phe (7.51–17.07 g/kg) improved the composition of the fillets in terms of flavor (free) amino acids, bound amino acids (especially EAA), and fatty acids (especially EPA and DHA); Phe (7.51–13.53 g/kg) increased muscle glycogen content (possibly related to the AMPK signaling pathway) and muscle protein deposition (possibly related to IGF-1/4EBP1/TOR and AKT/FOXOs signaling pathways). In conclusion, a diet with appropriate Phe levels could improve fillet quality.

Abstract Electric field-induced second harmonic generation allows electrically controlling nonlinear light-matter interactions crucial for emerging integrated photonics applications. Despite its wide presence in materials, the figures-of-merit of electric field-induced second harmonic generation are yet to be elevated to enable novel device functionalities. Here, we show that the polar skyrmions, a topological phase spontaneously formed in PbTiO3/SrTiO3 ferroelectric superlattices, exhibit a high comprehensive electric field-induced second harmonic generation performance. The second-order nonlinear susceptibility and modulation depth, measured under non-resonant 800 nm excitation, reach ~54.2 pm V−1 and ~664% V−1, respectively, and high response bandwidth (higher than 10 MHz), wide operating temperature range (up to ~400 K) and good fatigue resistance (>1010 cycles) are also demonstrated. Through combined in-situ experiments and phase-field simulations, we establish the microscopic links between the exotic polarization configuration and field-induced transition paths of the skyrmions and their electric field-induced second harmonic generation response. Our study not only presents a highly competitive thin-film material ready for constructing on-chip devices, but opens up new avenues of utilizing topological polar structures in the fields of photonics and optoelectronics.

Abstract Background The autophagy adapter SQSTM1/p62 is crucial for maintaining homeostasis in various organs and cells due to its protein–protein interaction domains and involvement in diverse physiological and pathological processes. Vascular endothelium cells play a unique role in vascular biology and contribute to vascular health. Methods Using the Cre-loxP system, we generated mice with endothelium cell-specific knockout of p62 mediated by Tek (Tek receptor tyrosine kinase)-cre to investigate the essential role of p62 in the endothelium. In vitro, we employed protein mass spectrometry and IPA to identify differentially expressed proteins upon knockdown of p62. Immunoprecipitation assays were conducted to demonstrate the interaction between p62 and FN1 or LAMC2 in human umbilical vein endothelium cells (HUVECs). Additionally, we identified the degradation pathway of FN1 and LAMC2 using the autophagy inhibitor 3-methyladenine (3-MA) or proteasome inhibitor MG132. Finally, the results of immunoprecipitation demonstrated that the interaction between p62 and LAMC2 was abolished in the PB1 truncation group of p62, while the interaction between p62 and FN1 was abolished in the UBA truncation group of p62. Results Our findings revealed that p62 Endo mice exhibited heart, lung, and kidney fibrosis compared to littermate controls, accompanied by severe cardiac dysfunction. Immunoprecipitation assays provided evidence of p62 acting as an autophagy adapter in the autophagy-lysosome pathway for FN1 and LAMC2 degradation respectively through PB1 and UBA domain with these proteins rather than proteasome system. Conclusions Our study demonstrates that defects in p62 within endothelium cells induce multi-organ fibrosis and cardiac dysfunction in mice. Our findings indicate that FN1 and LAMC2, as markers of (EndoMT), have detrimental effects on HUVECs and elucidate the autophagy-lysosome degradation mechanism of FN1 and LAMC2.

Jasmine (Jasminum sambac Aiton) is a well-known cultivated plant species for its fragrant flowers used in the perfume industry and cosmetics. However, the genetic basis of its floral scent is largely unknown. In this study, using PacBio, Illumina, 10× Genomics and high-throughput chromosome conformation capture (Hi-C) sequencing technologies, a high-quality chromosome-level reference genome for J. sambac was obtained, exploiting a double-petal phenotype cultivar ‘Shuangbanmoli’ (JSSB). The results showed that the final assembled genome of JSSB is 580.33 Mb in size (contig N50 = 1.05 Mb; scaffold N50 = 45.07 Mb) with a total of 39 618 predicted protein-coding genes. Our analyses revealed that the JSSB genome has undergone an ancient whole-genome duplication (WGD) event at 91.68 million years ago (Mya). It was estimated that J. sambac diverged from the lineage leading to Olea europaea and Osmanthus fragrans about 28.8 Mya. On the basis of a combination of genomic, transcriptomic and metabolomic analyses, a range of floral scent volatiles and genes were identified involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways. The results provide new insights into the molecular mechanism of its fragrance biosynthesis in jasmine.

Objective: To investigate the interrelationship between cardiovascular health awareness, risk perception, behavioural intention, and INTERHEART risk stratification in a middle-aged adult population in Malaysia. Methods: A cross-sectional survey with convenience sampling was conducted during November 2022 and January 2023. Participants completed validated questionnaires assessing cardiovascular health awareness, risk perception of cardiovascular diseases, behavioural intention towards adopting healthy habits, and INTERHEART risk stratification score (IHRS) based on established risk factors. A total of 602 respondents were included in the final analysis. Data were analysed with independent t-test/one-way ANOVA or Mann- Whitney/Kruskai-Wailis to test the differences, Pearson correlation or linear regression test to analyze the association of independent and dependent variables. Results: There was a significant positive correlation between medical knowledge related to cardiovascular disease (CVD) and knowledge related to CVD risk prevention, risk perception, behavioural intention and IHRS (P

Abstract Based on investment data from 214 sustainable universities in the United States, a study on the characteristics and affordability of universities with a willingness to invest in sustainability was conducted. First, according to the concept of ESG, the related factors of sustainability are classified. Then, the important variables are selected by the Cp method. Finally, the main characteristics and maximum affordability of universities with investment willingness for sustainability are quantitatively studied through the logit regression model. The findings are as follows: (1) Most universities take sustainable industries as their investment objective, promoting investment through a series of sustainable policies. (2) The characteristics of universities are as follows: (a) the size of the campus within a certain range; (b) sustainability instruction training for new employees; (c) the encouragement of employees for community service; and (d) the establishment of CIR (Committees on Investor Responsibility). (3) The maximum affordability is 30.3% of the total investment, and approximately 94% of universities do not actually invest as much in sustainability as in willingness. The study defines the identification factors of universities to provide an important basis for the formulation and implementation of guiding policies related to investment in the sustainability of universities in the future.

Abstract Background Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. Methods We retrospectively analyzed the data of 14,608 postmenopausal women aged 45–90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. Results Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51–60, 61–70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). Conclusions This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.

Abstract Background The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. Methods A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. Results Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904–0.965) and 0.927 (95% CI: 0.889–0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816–0.946) and 0.888 (95% CI: 0.810–0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. Conclusions Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.

Highlights An asymmetric membrane electrode based on phosphorene/MXene heterostructure-textured nanopiezocomposite was fabricated via a polar urea-assisted self-assembly strategy and additive manufacturing of the heterostructure beyond the skin effect. The merits of this novel asymmetric heterostructure-textured electrode and its intrinsic piezoelectricity were detailedly discussed. The stepwise lithiation process of phosphorene was revealed, and the enhanced electrochemical properties of this phosphorene-based nanopiezocomposite textured electrode were verified by the improved cycling stability and kinetics.

Abstract Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland–Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland–Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9–12). After the Bland–Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland–Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from − 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland–Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as − 0.287 ± 1.955, with the LoAs from − 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P

Abstract Cushing's syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non‐atherosclerotic myocardial infarction is rarely reported in Cushing's syndrome patients.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure–activity relationships of the compounds were also studied.

Summary: Spatial transcriptomics enables a single-cell resolution view of gene expression patterns in tissues, providing insight into their biological functions. However, applying this approach to the skin presents inherent challenges. Here, we present a protocol for preparing mammalian skin samples encompassing hair follicles for spatial transcriptomics. We describe steps for sample preparation, embedding, acquisition of frozen slices, RNA quality control, tissue mounting, fixation, staining, and imaging. We then detail procedures for permeabilization, reverse transcription, and cDNA collection.For complete details on the use and execution of this protocol, please refer to Chen et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

There are various types of land use in the agricultural and pastoral areas of northern China, including natural grassland and artificial grassland, scrub land, forest land and farmland, may change the soil microbial community However, the soil microbial communities in these different land use types remain poorly understood. In this study, we compared soil microbial communities in these five land use types within the agro-pastoral ecotone of northern China. Our results showed that land use has had a considerable impact on soil bacterial and fungal community structures. Bacterial diversity was highest in shrubland and lowest in natural grassland; fungal diversity was highest in woodland. Microbial network structural complexity also differed significantly among land use types. The lower complexity of artificial grassland and farmland may be a result of the high intensity of anthropogenic activities in these two land-use types, while the higher structural complexity of the shrubland and woodland networks characterised by low-intensity management may be a result of low anthropogenic disturbance. Correlation analysis of soil properties (e.g., soil physicochemical properties, soil nutrients, and microbiomass carbon and nitrogen levels) and soil microbial communities demonstrated that although microbial taxa were correlated to some extent with soil environmental factors, these factors did not sufficiently explain the microbial community differences among land use types. Understanding variability among soil microbial communities within agro-pastoral areas of northern China is critical for determining the most effective land management strategies and conserving microbial diversity at the regional level.

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood–brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p

Background This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. Methods and Results We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow‐up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257–0.365]; P

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

Ovarian cancer remains a significant health issue worldwide, often facing limitations in treatment due to side effects and drug resistance. Tumor cells typically undergo the “Warburg effect,” preferring glycolysis, which leads to their rapid growth and survival. Metformin, a widely used diabetes medication, targets 5' adenosine monophosphate‐activated protein kinase (AMPK), reducing glycolysis and thereby slowing tumor growth. Additionally, forkhead box protein K2 (FOXK2), a transcription factor often found in excess in many tumors, promotes glycolysis and tumor development. Delivering metformin and FOXK2 siRNA directly to the tumor site in the body is challenging due to the metformin's poor water solubility and the fragile nature of siRNA. To address this, zirconium and 5,10,15,20‐tetra(4‐pyridyl)porphyrin nanoparticles loaded with FOXK2 siRNA, enveloped in cell membrane, co‐encapsulated with metformin in gelatin methacrylate microspheres (ZrTCP@siFOXK2@CM/Met@GelMA) hydrogel microspheres are developed for effective dual delivery. These microspheres facilitate targeted drug delivery, photothermal therapy with near‐infrared light, and interference with glucose metabolism. These results show that infrared light combined with metformin and FOXK2 siRNA successfully activates the AMPK pathway, reducing ovarian cancer growth. This method offers a promising new direction in treatment, utilizing the complex metabolic characteristics of ovarian cancer to achieve better results.

Abstract Revealing the energy transfer (ET) process from excitons to rare earth ions in halide perovskites has great guiding value for designing optoelectronic materials. Here, the multiple ET channels in multi‐exciton emissive Sb3+/Nd3+ co‐doped Cs2ZrCl6 are explored to comprehend the ET processes. Förster–Dexter ET theory reveals that the sensitizer concentration rather than the overlap integral of the spectra plays the leading function in the comparison of the ET efficiency among multiple ET channels from the host self‐trapped excitons (STEs) and dopant triplet STEs to Nd3+ ions. Besides, Sb3+/Nd3+ co‐doped Cs2ZrCl6 enables varied color delivery and has great potential as anti‐counterfeiting material. Under X‐ray irradiation, Sb3+/Nd3+ co‐doped Cs2ZrCl6 presents a high light yield of ≈13300 photons MeV−1 and promising X‐ray imaging ability. This work provides new insight for investigating the ET efficiency among multiple ET processes and presents great potentiality of multi‐exciton emissive perovskites in the fields of anti‐counterfeiting and X‐ray imaging.