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Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) on a global scale has created a pressing demand for novel treatments. Gentianella turkestanorum (Gand.) Holub, a traditional Chinese herbal medicine, has been found to possess hypoglycemic effects. However, the mechanism of its action remains unclear. Objectives: This study was to investigate the impact and mechanism of G. turkestanorum 's water extract (WEG) in reducing insulin resistance (IR) in T2DM. Materials and Methods: Db/db mice were administered WEG for 8 weeks, during which their body weight, blood glucose (BG), oral glucose tolerance test, islet tolerance test, fasting insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein were monitored. Additionally, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in db/db mice were measured using enzyme-linked immunosorbent assay (ELISA). The study also evaluated the impact of WEG on liver injury through hematoxylin-eosin staining. The expression levels of key proteins and genes in both insulin signaling and inflammation-related pathways were detected using western blotting and real-time quantitative polymerase chain reaction. Results: WEG has the potential to regulate glycolipid metabolism, reduce inflammation, and alleviate IR. The mechanism of action may involve promoting the insulin signaling pathway and inhibiting inflammation. Conclusion: Gentianella turkestanorum could be a viable treatment option for T2DM and IR. [ABSTRACT FROM AUTHOR]

AbstractWe report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40–18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings. [ABSTRACT FROM AUTHOR]

Summary The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation‐targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A‐rearranged AML. With so many new drugs approved, the number of potential combinatorial approaches to leverage the maximal benefit of these agents has increased dramatically, while at the same time introducing clinical challenges, such as key preclinical and clinical data supporting the development of combinatorial therapy, how to optimally combine or sequence these novel agents, how to optimise dose and duration to maintain safety while enhancing efficacy, the optimal duration of therapy and the role of measurable residual disease in decision‐making in both intensive and low‐intensity therapy settings. In this review, we will outline the evidence leading to the approval of key agents in AML, their on‐label current approvals and how they may be optimally combined in a safe and deliverable fashion to further improve outcomes in AML. [ABSTRACT FROM AUTHOR]

Glass fiber‐reinforced resin matrix composites have good mechanical and impact resistance properties, while with particle co‐reinforcement, a synergistic effect can further improve their performance. In this paper, continuous glass fiber‐reinforced nylon 6 (GF/PA6) and continuous glass fiber (GF) with glass beads (GBs) co‐reinforced nylon 6 (GB–GF/PA6) were prepared to investigate the co‐reinforcement mechanism and the synergistic effect of particle and fiber. A quantitative parameter of the residual impact force divided by the critical force Pr/Pcr, as the damage degree of the low‐velocity impact, is defined to evaluate the impact resistance of the composite. The results indicate that the damage of GB–GF/PA6 was lower than that of GF/PA6, and the synergistic effect reaches the most obvious at the GB addition of 10 wt%. Scanning electron microscope (SEM) and x‐ray computed tomography (XCT) images disclose that GB impedes the type II crack spread in the matrix and fiber/matrix interface. With the type II cracks reducing, the materials' resistance to delamination can be significantly enhanced. For the composite structure, in which 10 wt% GB and 60 wt% GF are introduced, the flexural strength, shear strength, and pendulum impact strength were tested with the maximum values of 379.4 MPa, 53.1 MPa, and 219.0 J/m2, respectively. This composite structure design, presenting a continuous GF and GBs co‐reinforce effect, offers a manufacturing process that is easily scalable to achieve excellent characteristics. [ABSTRACT FROM AUTHOR]

Tagraxofusp is a first‐in‐class CD123‐directed conjugate of an amended diphtheria toxin platform and recombinant interleukin 3. Binding and subsequent internalization of the drug result in cell death via disruption of intracellular protein synthesis. CD123 is a surface marker that is expressed in several hematological malignancies, especially blastic plasmacytoid dendritic cell neoplasm (BPDCN), where its expression is ubiquitous. A pivotal study of tagraxofusp in BPDCN resulted in its approval for the treatment of BPDCN, the first treatment approved for this indication. Since the introduction of tagraxofusp, research has focused on the management of adverse effects, combination therapy to improve outcomes in fit patients, and dosing and combination strategies to mitigate toxicities while preserving efficacy, especially among older patients. The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123‐positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. Results: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. Conclusions: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis. [ABSTRACT FROM AUTHOR]

Summary Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7–15.9] vs. 19.0 months [95% CI, 16.1–23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability over time. [ABSTRACT FROM AUTHOR]

DNA modifications add another layer of complexity to the eukaryotic genome to regulate gene expression, playing critical roles as epigenetic marks. In eukaryotes, the study of DNA epigenetic modifications has been confined to 5mC and its derivatives for decades. However, rapid developing approaches have witnessed the expansion of DNA modification reservoirs during the past several years, including the identification of 6mA, 5gmC, 4mC, and 4acC in diverse organisms. However, whether these DNA modifications function as epigenetic marks requires careful consideration. In this review, we try to present a panorama of all the DNA epigenetic modifications in eukaryotes, emphasizing recent breakthroughs in the identification of novel DNA modifications. The characterization of their roles in transcriptional regulation as potential epigenetic marks is summarized. More importantly, the pathways for generating or eliminating these DNA modifications, as well as the proteins involved are comprehensively dissected. Furthermore, we briefly discuss the potential challenges and perspectives, which should be taken into account while investigating novel DNA modifications. [ABSTRACT FROM AUTHOR]

Aims: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, but its pathogenesis remains incompletely understood, particularly the involvements of central nervous system sensitization in colorectal visceral pain. Our study was to investigate whether the paraventricular thalamus (PVT) projected to the insular cortex (IC) to regulate colorectal visceral pain in neonatal colonic inflammation (NCI) mice and underlying mechanisms. Methods: We applied optogenetic, chemogenetic, or pharmacological approaches to manipulate the glutamatergicPVT‐IC pathway. Fiber photometry was used to assess neuronal activity. Electromyography activities in response to colorectal distension (CRD) were measured to evaluate the colorectal visceral pain. Results: NCI enhanced c‐Fos expression and calcium activity upon CRD in the ICGlu, and optogenetic manipulation of them altered colorectal visceral pain responses accordingly. Viral tracing indicated that the PVTGlu projected to the ICGlu. Optogenetic manipulation of PVTGlu changed colorectal visceral pain responses. Furthermore, selective optogenetic modulation of PVT projections in the IC influenced colorectal visceral pain, which was reversed by chemogenetic manipulation of downstream ICGlu. Conclusions: This study identified a novel PVT‐IC neural circuit playing a critical role in colorectal visceral pain in a mouse model of IBS. [ABSTRACT FROM AUTHOR]

Spherical micro/nanorobots are reported as attractive candidates in nano‐surgery, contamination degradation, analytical chemistry, medical engineering, etc. Unlike macroscopic robots, the standard fabrication and inspection strategy to control the high quality of microrobots are rarely explored before. Overcoming the geometrical discrepancy is now essential to keep an identical locomotion behavior for spherical microrobot individuals for complex usages. Herein, acoustic‐based microbubble grippers are proposed controlled by a machine vision system to realize agile recognition and sorting of unqualified spherical microrobot models. Theoretical analysis and numerical simulation reveal the basic grabbing mechanisms via acoustic stimuli. The acoustic resonation of microbubbles can generate a locally enhanced acoustic field, attracting microrobots toward the bubble surface by the acoustic forces. The viscosity of microfluid makes it possible to instantaneously grab or release just by controlling the microbubble activation. Further, a machine vision‐based monitor and control system is proposed to enable automatic control for the entire process. Based on extracted characteristic parameters, target microrobot models are quickly selected and grabbed out. It is expected that such a combination of microgrippers with an advanced control system will pave the way for high‐qualified inspection for microrobots and improve their unique versatility in myriad micromanipulation scenarios. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NETs). It has been shown to be effective and well tolerated in patients with metastatic NETs in several centres in the USA, Europe, and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. Methods: One hundred and seven (107) patients with metastatic NETs who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST 1.1 and qualitative analysis were examined. The overall and progression-free survival curves were also evaluated. Results: The median progression-free survival was 49 months. Response assessment after completion of treatment showed that 33 (37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression-free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. Conclusion: Our results show that PRRT is safe and effective in the treatment of metastatic NET in the Asian population. There was a significant difference in the progression-free survival curves between low-grade and high-grade NET and in the progression-free and overall survival comparing the number of cycles received. [ABSTRACT FROM AUTHOR]

• Ketamine-induced anxiety and impairment in mice reveal distinct proteomics in different brain regions. • Alterations in prefrontal cortex proteins may be primarily associated with immuno-inflammatory processes. • Proteins associated with synaptic plasticity and mitochondrial function are predominantly regulated in the hippocampus. • Changes were observed in the expression levels of glutamatergic system-related proteins in the hippocampus. Schizophrenia, a complex psychiatric disorder with diverse symptoms, has been linked to ketamine, known for its N-methyl-D-aspartate (NMDA) receptor antagonistic properties. Understanding the distinct roles and mechanisms of ketamine is crucial, especially regarding its induction of schizophrenia-like symptoms. Recent research highlights the impact of ketamine on key brain regions associated with schizophrenia, specifically the prefrontal cortex (PFC) and hippocampus (Hip). This study focused on these regions to explore proteomic changes related to anxiety and cognitive impairment in a chronic ketamine-induced mouse model of schizophrenia. After twelve consecutive days of ketamine administration, brain tissues from these regions were dissected and analyzed. Using tandem mass tag (TMT) labeling quantitative proteomics techniques, 34,797 and 46,740 peptides were identified in PFC and Hip, corresponding to 5,668 and 6,463 proteins, respectively. In the PFC, a total of 113 proteins showed differential expression, primarily associated with the immuno-inflammatory process, calmodulin, postsynaptic density protein, and mitochondrial function. In the Hip, 129 differentially expressed proteins were screened, mainly related to synaptic plasticity proteins and mitochondrial respiratory chain complex-associated proteins. Additionally, we investigated key proteins within the glutamatergic synapse pathway and observed decreased expression levels of phosphorylated CaMKII and CREB. Overall, the study unveiled a significant proteomic signature in the chronic ketamine-induced schizophrenia mouse model, characterized by anxiety and cognitive impairment in both the PFC and Hip, and this comprehensive proteomic dataset may not only enhance our understanding of the molecular mechanisms underlying ketamine-related mental disorders but also offer valuable insights for future disease treatments. [ABSTRACT FROM AUTHOR]

This research proposes a new method to solve group decision-making(GDM) problems with intuitionistic fuzzy preference relations(IFPRs). First, a new definition of multiplicative consistency of IFPR is presented to address the defects of the existing consistency definitions. Then, two programming models are established to obtain the most optimistic and pessimistic consistent IFPRs and corresponding intuitionistic fuzzy priority weights. Also, in order to improve the accuracy of aggregate information, a new method to determine the weights of decision-makers(DMs) is offered by considering the interaction among DMs. Subsequently, by combining the vagueness and non-vagueness of the aggregated information, a multiplicative consistency definition of the collective IFPR is provided. Moreover, to simplify the GDM process, a programming model for solving the priority weight is established, which effectively avoids the consistency test and correction of IFPRs. Finally, the values of the proposed method are illustrated by comparative analysis. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19–3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease. [ABSTRACT FROM AUTHOR]

Background: Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. Methods: This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. Results: The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. Conclusions: The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses' development. [ABSTRACT FROM AUTHOR]

[Display omitted] • A simple and effective method for the synthesis of 3D heterogeneous structures. • The synergistic effect between the components improves the activity of the material. • The catalyst depicts exceptional performance in all three reactions of OER, HER, and overall water splitting. • The electrocatalytic mechanism of HER and OER was studied by DET calculation. Exploiting efficient and economical electrocatalysts is indispensable to promoting the sluggish kinetics of overall water-splitting. Herein, we designed a phosphate reaction and two-step hydrothermal method to construct a 3D porous clustered flower-like heterogeneous structure of NiFe-layered double hydroxide (NiFe) and CoP 2 @MnP (CMP) grown in-situ on MXene-modified nickel foam (NF) substrate (denoted as NiFe/CMP/MX), with favorable kinetics. Density functional theory calculations (DFT) demonstrate that the self-driven transfer of heterojunction charges causes electron redistribution of the catalyst, and optimizes the electron transfer rate of the active site and the d-band center near the Fermi level, thereby reducing the adsorption energy of H and O reaction intermediates (H*, OH*, OOH*). As expected, the combination of CMP and NiFe with naturally conductive MXene forms a strong chemical and electron synergistic effect, which enables the synthesized NiFe/CMP/MX heterogeneous structure exhibits good activity for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with a low overpotential of 200 mV and 126 mV at 10 mA cm−2, respectively. Furthermore, the overpotential of 1.58 V is enough to drive a current density of 10 mA cm−2 in a two-electrode configuration, which is better than noble metals (RuO 2 (+)//Pt/C(−)) (1.68 V). [ABSTRACT FROM AUTHOR]

Evidence on the influence of patient characteristics on HbA1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium–glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA1c reduction ≥ 1% at 6th month, HbA1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA1c, patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A novel type of A‐type nanogrids (AGs) with axial and central chirality was synthesized via Friedel‐Crafts gridization of thiophenes and difluorenyl biaromatic derivatives, yielding 9%—30%. Additionally, the effect of stereoisomers of 1,1'‐binaphthyl difluorenols (BINDFOH) was investigated to demonstrate that R/S‐BINDFOH is more advantageous for the synthesis of AGs than Mix‐BINDFOH. Furthermore, tests on OFET memory devices showed that AGs have a larger storage window, indicating potential for data storage applications. [ABSTRACT FROM AUTHOR]

Herein, the concept of ionic cross-linking was first introduced into the preparation of thermoplastic vulcanizates (TPV). Oil-resistant TPV was developed based on acrylate rubber (ACM) and polyoxymethylene formaldehyde (POM) using Ca(OH)2 as the cross-linking agent. The physical and mechanical properties, aging resistance, dynamic mechanical properties, micromorphology, and energy loss of the composites under covalent cross-linking networks and ion cross-linking networks with different degrees of cross-linking were systematically studied. The results showed that Ca2+ could form metal ion binding with the -COOH of ACM, playing a cross-linking role for ACM. Compared with the covalent bonding system, the 100% constant tensile stress of TPV in the ionic bonding system can be increased by 31% and the elongation increased by 14.5%. And exhibits better elasticity and lower hysteresis loss below 140 °C. The increase in dispersed phase modulus increases the phase domain of dispersed phase, weakens the binding with matrix, weakens the tensile strength, increases the intrusion of hot oxygen and hot oil, increases the energy storage modulus, and decreases the loss modulus. [ABSTRACT FROM AUTHOR]

One of the key challenges in laser powder bed fusion (LPBF) additive manufacturing of metals is the appearance of microscopic pores in 3D-printed metallic structures. Quality control in LPBF can be accomplished with non-destructive imaging of the actual 3D-printed structures. Thermal tomography (TT) is a promising non-contact, non-destructive imaging method, which allows for the visualization of subsurface defects in arbitrary-sized metallic structures. However, because imaging is based on heat diffusion, TT images suffer from blurring, which increases with depth. We have been investigating the enhancement of TT imaging capability using machine learning. In this work, we introduce a novel multi-task learning (MTL) approach, which simultaneously performs the classification of synthetic TT images, and segmentation of experimental scanning electron microscopy (SEM) images. Synthetic TT images are obtained from computer simulations of metallic structures with subsurface elliptical-shaped defects, while experimental SEM images are obtained from imaging of LPBF-printed stainless-steel coupons. MTL network is implemented as a shared U-net encoder between the classification and the segmentation tasks. Results of this study show that the MTL network performs better in both the classification of synthetic TT images and the segmentation of SEM images tasks, as compared to the conventional approach when the individual tasks are performed independently of each other. [ABSTRACT FROM AUTHOR]

Background: Adipose insulin resistance (Adipo-IR) is associated with multiple metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The study aimed to evaluate sex differences in the association between Adipo-IR and NAFLD, and further investigated other potential modifiers. Methods: This cross-sectional study enrolled adults without diabetes who underwent physical examinations in Beijing Chao-Yang Hospital. We calculated the Adipo-IR index as the product of the fasting insulin and free fatty acid concentration. We categorized Adipo-IR into four groups according to quartiles, using the first interquartile range (Q1) as the reference. Logistic regression was used stratified by the modifiers after adjustment for potential confounders. Results: There were 5586 participants in the study, 49.8% (n = 2781) of whom were women and 30.4% (n = 1698) with NAFLD. There was a graded positive association between Adipo-IR and NAFLD, with sex (P = 0.01) and hyperlipidemia (P = 0.02) modifying this association. In the hyperlipidemic women, for one unit increase in log-Adipo-IR, the odds of having NAFLD increased by 385% after adjustment for potential confounders (OR = 4.85, 95%CI 3.54–6.73, P < 0.001). However, it turned out that the odds of having NAFLD increased by 131% (OR = 2.31, 95%CI 1.74–3.11, P < 0.001), 216% (OR = 3.16, 95%CI 2.56–3.93, P < 0.001), 181% (OR = 2.81, 95%CI 1.88–4.28, P < 0.001) in normolipidemic men, hyperlipidemic men, and normolipidemic women, respectively. Similarly, the ORs for the association between Adipo-IR and NAFLD in women with age ≥ 50 years were higher than ORs in women with age < 50 years. Conclusions: The positive correlation between Adipo-IR and NAFLD was stronger in hyperlipidemic women, compared with normolipidemic or hyperlipidemic men, or normolipidemic women. The association also strengthened for women over 50 years. Treatment strategies targeting Adipo-IR to alleviate NAFLD may be of value, especially in hyperlipidemic women after menopause. Plain language summary: In our study, we focused on non-alcoholic fatty liver disease (NAFLD), a condition characterized by excessive fat in the liver not caused by alcohol use. NAFLD is often connected to problems with how our body uses insulin, a hormone that helps regulate sugar levels. Adipose insulin resistance (Adipo-IR), or the inability of adipose cells to respond properly to insulin, can lead to more fat getting stored in the liver, worsening NAFLD. Previous research has indicated that NAFLD risk factors and outcomes can vary between sexes. For example, men are generally more susceptible to NAFLD during their reproductive years, whereas postmenopausal women have a risk level similar to or even exceeding that of men. We were particularly interested in how Adipo-IR affects the risk and progression of NAFLD differently in men and women. We conducted a large-scale study involving over 5,000 Chinese adults without diabetes. Our findings reveal a stronger association between Adipo-IR and NAFLD in women, especially in those with high lipid levels in their blood or who are over 50 years. This implies that treatments targeting Adipo-IR, such as weight loss strategies and certain medications, such as thiazolidinediones, might be particularly effective for these groups of women. Given the rising global prevalence of NAFLD, our research offers valuable insights for tailoring treatment strategies and could help identify which populations would benefit most from targeted interventions to mitigate the disease. Highlights: Adipo-IR is positively correlated with NAFLD in subjects without diabetes. The positive association between Adipo-IR and NAFLD is sex-specific, and it strengthened for hyperlipidemic women. Among all the lipid indicators, low-density lipoprotein cholesterol acted as the main modifier. The association also strengthened for women over 50 years compared with women less than 50 years. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy preparation and delivery is an enormously complex operation involving multiple teams. The complexity and safety requirements often impact on the timeliness of treatment. We aimed to take a human-centric approach and examine the processes required for chemotherapy provision. We identified key areas to redesign to improve the efficiency of care delivery. These included preparing chemotherapy in advance, optimizing scheduling and creating a data-driven system of continuous improvement. Introduction: Chemotherapy is complex. We hypothesized that a design thinking approach could redesign preparatory processes and reduce wait times. Methods: A multidisciplinary process mapping exercise was undertaken to understand the current processes, followed by proposing and testing solutions. Proposals were selected based on desirability and feasibility. These focused on starting the morning treatments on time and scheduling pre-made regimens in these slots. The primary outcome measure was the time from the appointment to starting treatment. Treatments in the post-intervention study group were compared against a historical control group. Results: The median time to start morning treatment decreased by 46%, from 83 min (with an interquartile range 50–127) in the control group to 45 min (with an interquartile range of 24–81 min) in the study group (p < 0.001). This translated into an overall improvement for the day, with the median time to start treatment decreasing from 77 min (with an interquartile range of 40–120 min) to 47 min (with an interquartile range of 20–79 min) (p < 0.001). Pre-makes increased by 258%, from 908 (28.5%) to 2340 (71.7%) regimens (p < 0.001). The number of patients starting treatment within an hour of their appointment increased from 1688 (32.8%) to 3355 (62.3%, p < 0.001). Conclusion: We have shown that a data-driven, design thinking approach can improve waiting times. This can be adapted to improve other processes in an empathetic, sustainable manner. [ABSTRACT FROM AUTHOR]

Magnesium metal batteries are promising candidates for next‐generation high‐energy‐density and low‐cost energy storage systems. Their application, however, is precluded by infinite relative volume changes and inevitable side reactions of Mg metal anodes. These issues become more pronounced at large areal capacities that are required for practical batteries. Herein, for the first time, double‐transition‐metal MXene films are developed to promote deeply rechargeable magnesium metal batteries using Mo2Ti2C3 as a representative example. The freestanding Mo2Ti2C3 films, which are prepared using a simple vacuum filtration method, possess good electronic conductivity, unique surface chemistry, and high mechanical modulus. These superior electro‐chemo‐mechanical merits of Mo2Ti2C3 films help to accelerate electrons/ions transfer, suppress electrolyte decomposition and dead Mg formation, as well as maintain electrode structural integrity during long‐term and large‐capacity operation. As a result, the as‐developed Mo2Ti2C3 films exhibit reversible Mg plating/stripping with high Coulombic efficiency of 99.3% at a record‐high capacity of 15 mAh cm−2. This work not only sheds innovative insights into current collector design for deeply cyclable Mg metal anodes, but also paves the way for the application of double‐transition‐metal MXene materials in other alkali and alkaline earth metal batteries. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is one of the leading causes of death worldwide. This study explored the relationship between the MIR31HG gene polymorphisms and the risk of BC in Chinese women. Methods: Eight single nucleotide polymorphisms (SNPs) in MIR31HG were genotyped among 545 patients with BC and 530 healthy controls using Agena MassARRAY analysis. The PLINK software was used to calculate the odds ratio (OR) and 95% confidence intervals (CIs) via the logistic regression analysis. Multi-factor dimensionality reduction (MDR) analysis was performed to study the impact of SNP-SNP interaction on BC risk. Results: MIR31HG rs72703442-AA (OR 0.29, 95% CI 0.10–0.79, p = 0.026), rs55683539-TT (OR 0.46, 95% CI 0.26–0.80, p = 0.012) and rs2181559-AA (OR 0.59, 95% CI 0.40–0.89, p = 0.038) were associated with a reduced risk of BC in Chinese women, as well as stratified results at age ≥ 52 years. Rs79988146 was correlated with estrogen receptor (ER) and progesterone receptor (PR)in Chinese female BC patients under various genetic models. Age at menarche stratification indicated that rs1332184 was associated with increased risk in BC patients, whereas stratification by number of births indicated that rs10965064 was associated with reduced risk in BC patients. MDR analysis showed that the best single-locus model for predicting of BC risk are rs55683539, which, rs55683539-CC group was a high risk group and rs55683539-TT group was a low risk group. Conclusions: The results indicated that the MIR31HG polymorphisms were associated with a reduced risk of BC in Chinese women. [ABSTRACT FROM AUTHOR]

With the rapid development of the information age, software vulnerabilities have threatened the safety of communication and mobile network, and research on vulnerability repair is urgent. Different from the existing machine learning-based approaches, we propose VulRep, a vulnerability repair approach based on vulnerability introduction, which combines empirical research findings on vulnerability inducing and vulnerability fixing commit with machine learning approaches for vulnerability repair. Firstly, we construct the vulnerability introduction and repair dataset, and generate the AST tree for the code of inducing commit and fixing commit to form a sequence after abstraction processing, and input it into the Transformer model to generate a recommendation list through beam search. After filling in the abstracted code, it is combined with the rules defined by empirical research findings, and the final patch is obtained after verification. Experimental results show that VulRep can improve the performance of repairing vulnerabilities, which illustrates the effectiveness of combined empirical research findings. In addition, we found that our approach is more suitable for repairing type CWE-119 (Improper Restriction of Operations within the Bounds of a Memory Buffer) vulnerabilities and can perform vulnerability repair better. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized in a rat model of visceral hypersensitivity induced by neonatal colonic inflammation (NCI). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for melatonin (MT) in sensitization of sodium channels in NCI rats. Methods: Colorectal distention (CRD) in adult male rats as a measure of visceral hypersensitivity. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. Western blot and Immunofluorescence were employed to detect changes in expression of Nav1.8 and MT2. Results: The results showed that rats exhibited visceral hypersensitivity after NCI treatment. Intrathecal application of melatonin significantly increased the threshold of CRD in NCI rats with a dose-dependent manner, but has no role in the control group. Whole-cell patch clamp recording showed that melatonin remarkably decreased the excitability and the density of TTX-R sodium channel in DRG neurons from NCI rats. The expression of MT2 receptor at the protein level was markedly lower in NCI rats. 8MP, an agonist of MT2 receptor, enhanced the distention threshold in NCI rats. Application of 8MP reversed the enhanced hypersensitivity of DRG neurons from NCI rats. 8MP also reduced TTX-R sodium current density and modulated dynamics of TTX-R sodium current activation. Conclusions: These data suggest that sensitization of sodium channels of colon DRG neurons in NCI rats is most likely mediated by MT2 receptor, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS. [ABSTRACT FROM AUTHOR]

Multiplicative noise removal is a quite challenging problem in image denoising. In recent years, hyper-Laplacian prior information has been successfully introduced in the image denoising problem and significant denoising effects have been achieved. In this paper, we propose a new hybrid regularizer model for removing multiplicative noise. The proposed model consists of the non-convex higher-order total variation and overlapping group sparsity on a hyper-Laplacian prior regularizer. It combines the advantages of the non-convex regularization and the hybrid regularization, which may simultaneously preserve the fine-edge information and reduce the staircase effect at the same time. We develop an effective alternating minimization method for the proposed nonconvex model via an alternating direction method of multipliers framework, where the majorization–minimization algorithm and the iteratively reweighted algorithm are adopted to solve the corresponding subproblems. Numerical experiments show that the proposed model outperforms the most advanced model in terms of visual quality and certain image quality measurements. [ABSTRACT FROM AUTHOR]

The low ionic conductivity of poly(ethylene oxide) (PEO)‐based polymer electrolytes at room temperature and the undesired lithium‐dendrite growth at Li|PEO interface impede their further application. Herein, a PEO polymer is regulated at the molecular level through a copper ion (Cu2+) coordination effect with both PEO and Li salts to achieve a high Li+ conductivity of 0.2 mS cm−1 and a transference number of 0.42 at 30 °C. Moreover, the Cu‐coordinated PEO electrolyte is neither sticky nor hygroscopic because the hydrophilic oxygen groups in PEO are terminated by Cu ions. Furthermore, the in situ formed F/Li‐rich inorganic layer induced by CuF2 additive accelerates Li+ transport kinetics and enables uniform Li+ deposition during Li plating/stripping. As a result, the Cu2+‐coordinated PEO electrolytes deliver a high critical current density of 1.5 mA cm−2 at 30 °C. An all‐solid‐state Li‐LiNi0.83Co0.12Mn0.05O2 (NCM83) battery with such a copper coordinated PEO electrolyte exhibits a long cycle life over 500 cycles with a capacity retention of 71% under 0.6 C at 30 °C. When the mass loading increases to a record high of 7 mg cm−2, the Li‐NCM83 cell delivers a high areal capacity of 1.07 mAh cm−2 under 0.1 C at 30 °C. [ABSTRACT FROM AUTHOR]

[Display omitted] • CoFePBA with hierarchical hollow structure was prepared by anion exchange method. • The nanocomposite with hollow structure was prepared by heat-treatment of CoFePBA. • The synergistic effect among different components significantly enhanced OER activity. The microstructure of materials importantly affects their performance. As electrocatalyst materials, the performance of hollow-structure materials is usually better than that of solid materials because of the larger specific surface area, lower density, and more exposed active sites of hollow structure. Bimetallic catalysts usually exhibit better catalytic activity than monometallic catalysts because of the synergistic effects between different metal elements. Prussian blue and its analogues (PB/PBAs) are ideal precursors for preparing hollow-structure bimetallic catalysts due to their structure and composition characteristics. In this study, ZIF-67 hollow sphere (HS) was used as the template to prepare hierarchical hollow CoFePBA (H-SCP) through anion-exchange method. The oxygen evolution reaction (OER) catalytic performance of H-SCP was further improved by low-temperature heat treatment in N 2 atmosphere. The H-SCP-350 sample, which was obtained at a heat-treatment temperature of 350 ℃, was a bimetallic nanocomposite. Part of H-SCP was converted into metallic cobalt and cobalt-iron alloy during heat treatment. The synergistic effect among the different components effectively improved the electrocatalytic activity of the material. Therefore, H-SCP-350 showed the best OER catalytic performance among all samples. The overpotential was only 291mV at a current density of 10 mA cm−2 when tested in 1 M KOH electrolyte. [ABSTRACT FROM AUTHOR]

Whole‐organ transcriptomic analyses have emerged as a common method for characterizing developmental transitions in mammalian organs. However, it is unclear if all cell types in an organ follow the whole‐organ defined developmental trajectory. Recently, a postnatal two‐stage developmental process was described for the mouse stomach. Here, using laser capture microdissection to obtain in situ transcriptomic data, we show that mouse gastric pit cells exhibit four postnatal developmental stages. Interestingly, early stages are characterized by the up‐regulation of genes associated with metabolism, a functionality not typically associated with pit cells. Hence, beyond revealing that not all constituent cells develop according to the whole‐organ determined pathway, these results broaden our understanding of the pit cell phenotypic landscape during stomach development. [ABSTRACT FROM AUTHOR]

Plasmon‐enhanced electrochemiluminescence (ECL) at the single‐nanoparticle (NP) level was investigated by ECL microscopy. The Au NPs were assembled into an ordered array, providing a high‐throughput platform that can easily locate each NP in sequential characterizations. A strong dependence of ECL intensity on Au NP configurations was observed. We demonstrate for the first time that at the single‐particle level, the ECL of Ru(bpy)32+‐TPrA was majorly quenched by small Au NPs (<40 nm), while enhanced by large Au ones (>80 nm) due to the localized surface plasmon resonance (LSPR). Notably, the ECL intensity was further increased by the coupling effect of neighboring Au NPs. Finite Difference Time Domain (FDTD) simulations conformed well with the experimental results. This plasmon enhanced ECL microscopy for arrayed single NPs provides a reliable tool for screening electrocatalytic activity at a single particle. [ABSTRACT FROM AUTHOR]

Plasmon‐enhanced electrochemiluminescence (ECL) at the single‐nanoparticle (NP) level was investigated by ECL microscopy. The Au NPs were assembled into an ordered array, providing a high‐throughput platform that can easily locate each NP in sequential characterizations. A strong dependence of ECL intensity on Au NP configurations was observed. We demonstrate for the first time that at the single‐particle level, the ECL of Ru(bpy)32+‐TPrA was majorly quenched by small Au NPs (<40 nm), while enhanced by large Au ones (>80 nm) due to the localized surface plasmon resonance (LSPR). Notably, the ECL intensity was further increased by the coupling effect of neighboring Au NPs. Finite Difference Time Domain (FDTD) simulations conformed well with the experimental results. This plasmon enhanced ECL microscopy for arrayed single NPs provides a reliable tool for screening electrocatalytic activity at a single particle. [ABSTRACT FROM AUTHOR]

To study the safety of improved hydrodissection based on the periparathyroidal fascial space during microwave ablation (MWA) for secondary hyperparathyroidism (SHPT). Data from 337 patients (162 males and 175 females; mean age, 50.8 ± 12.8 [range, 16-84] years) who underwent MWA for SHPT were retrospectively reviewed. Among them, 177 patients underwent traditional hydrodissection (traditional group) and 160 patients underwent improved hydrodissection based on periparathyroidal fascial spaces (improved group). Safety enhancement was analyzed by comparing the complications between the two groups. The characteristics of the hydrodissected fascial spaces, complications, and the follow-up results were recorded. The baseline data, clinical parameters, laboratory indices and characteristics of SHPT lesions were analyzed to assess the risk factors associated with hoarseness. Hydrodissection was successfully performed in all the enrolled patients according to the protocol. Six periparathyroid fascial spaces were hydrodissected, depending on the location of the SHPT lesions. The incidence of hoarseness due to recurrent laryngeal nerve injury, the most common complication of thermal ablation for SHPT lesions, was lower in the improved group than in the traditional group (6.9% vs. 13.0%, p = 0.044). The median hoarseness recovery time in the improved group was shorter than that in the traditional group (2 vs. 6 months, p < 0.001). There was no difference in technical efficiency between the two groups (improved group vs. traditional group: 75.0% vs. 70.6%; p > 0.05). Compared with traditional hydrodissection, improved hydrodissection based on periparathyroidal fascial spaces could enhance safety during MWA for SHPT. [ABSTRACT FROM AUTHOR]

To study the efficacy and safety of an improved hydrodissection protocol based on the perithyroidal fascial space during microwave ablation for papillary thyroid carcinoma (PTC). The data of 341 patients (94 men and 247 women, median age 41 years old, 25%–75% interquartile range 34–53 years old, nodule maximum diameter 0.2–1.9 cm) who underwent microwave ablation for PTC were retrospectively reviewed. Among them, 185 patients underwent traditional hydrodissection and served as a control group, and 156 patients underwent improved hydrodissection based on perithyroidal fascial spaces, constituting the improved group. Improvements in safety were analyzed by comparing complications between the two groups. The characteristics of hydrodissected spaces, complications, and follow-up results were recorded. Hydrodissection was successfully performed in all enrolled patients according to the protocol. The incidence of hoarseness caused by recurrent laryngeal nerve injury, the most common complication in thermal ablation of thyroid nodules, was significantly lower in the improved group than in the control group (1.9% vs. 8.1%, p = 0.021). The median hoarseness recovery time in the improved group was shorter than that in the control group (2 months vs. 3 months, p = 0.032). During follow-up, no local recurrence was encountered in either group. The tumor disappearance rate was not significantly different between the two groups (69.9% vs. 75.7%, p = 0.228). Improved hydrodissection based on perithyroidal fascial spaces had better protective effects than traditional hydrodissection. [ABSTRACT FROM AUTHOR]

Background: The major mechanisms of dementia and cognitive impairment are vascular and neurodegenerative processes. Early diagnosis of cognitive impairment can facilitate timely interventions to mitigate progression.Objective: This study aims to develop a reliable machine learning (ML) model using socio-demographics, vascular risk factors, and structural neuroimaging markers for early diagnosis of cognitive impairment in a multi-ethnic Asian population.Methods: The study consisted of 911 participants from the Epidemiology of Dementia in Singapore study (aged 60- 88 years, 49.6% male). Three ML classifiers, logistic regression, support vector machine, and gradient boosting machine, were developed. Prediction results of independent classifiers were combined in a final ensemble model. Model performances were evaluated on test data using F1 score and area under the receiver operating curve (AUC) methods. Post modelling, SHapely Additive exPlanation (SHAP) was applied on the prediction results to identify the predictors that contribute most to the cognitive impairment prediction.Findings: The final ensemble model achieved a F1 score and AUC of 0.87 and 0.80 respectively. Accuracy (0.83), sensitivity (0.86), specificity (0.74) and predictive values (positive 0.88 negative 0.72) of the ensemble model were higher compared to the independent classifiers. Age, ethnicity, highest education attainment and neuroimaging markers were identified as important predictors of cognitive impairment.Conclusion: This study demonstrates the feasibility of using ML tools to integrate multiple domains of data for reliable diagnosis of early cognitive impairment. The ML model uses easy-to-obtain variables and is scalable for screening individuals with a high risk of developing dementia in a population-based setting. [ABSTRACT FROM AUTHOR]

• RIS-GAN is proposed for the self-supervised learning of generative adversarial networks. • RIS-GAN greatly improves the quality of extracted features and generated images. • RIS-GAN brings the network more stable training property. Self-supervised methods play a vital role in representation learning without the need for annotated data and learn feature representations where data itself provides supervision. However, it is still challenging for the discriminator to learn reliable representations. To address this issue, we propose the self-supervised GANs via recovering initial state of subimages (RIS-GAN). Recovering initial state (RIS) task requires the network to recover the original state information of each sub-part of a composite image. Specifically, the network should predict the rotation angle and the initial position of subimages, and also predict which original image each subimage belongs to. To recover these information, the network should capture intra-image and inter-image information and extract high-similarity features between those patches belonging to the same original images. Besides, we propose local-discriminator, to improve the ability of the discriminator to judge global features from local patch features. To accomplish the above task, our proposed model should extract multi-level information to improve the understanding of image structure and content, and the ability to mine valuable information from image patches. We experimentally demonstrate the state-of-the-art performance of our RIS-GAN with respect to other self-supervised GAN methods on CIFAR-10, ImageNet 32 × 32, CelebA, and STL-10 datasets. [ABSTRACT FROM AUTHOR]

To solve the problem of fault signals of wind turbine bearings being weak, not easy to extract, and difficult to identify, this paper proposes a fault diagnosis method for fan bearings based on Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) and Grey Wolf Algorithm Optimization Kernel Extreme Learning Machine (GWO-KELM). First, eliminating the interference of noise on the collected vibration signal should be conducted, in which the wavelet threshold denoising approach is used in order to reduce the noise interference with the vibration signal. Next, CEEMDAN is used to decompose the signal after a denoising operation to obtain the multi-group intrinsic mode function (IMF), and the feature vector is selected by combining the correlation coefficients to eliminate the spurious feature components. Finally, the fuzzy entropy for the chosen IMF component is input into the GWO-KELM model as a feature vector for defect detection. After diagnosing the Case Western Reserve University (CWRU) dataset by the method presented in this research, it is found that the method can identify 99.42% of the various bearing states. When compared to existing combination approaches, the proposed method is shown to be more efficient for diagnosing wind turbine bearing faults. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) related chronic visceral pain affects 20% of people worldwide. The treatment options are very limited. Although the scholarly reviews have appraised the potential effects of the intestinal microbiota on intestinal motility and sensation, the exact mechanism of intestinal microbiota in IBS-like chronic visceral pain remains largely unclear. The purpose of this study is to investigate whether Folic Acid (FA) attenuated visceral pain and its possible mechanisms. Chronic visceral hyperalgesia was induced in rats by neonatal colonic inflammation (NCI). 16S rDNA analysis of fecal samples from human subjects and rats was performed. Patch clamp recording was used to determine synaptic transmission of colonic-related spinal dorsal horn. Alpha diversity of intestinal flora was increased in patients with IBS, as well as the obviously increased abundance of Clostridiales order (a main bacteria producing hydrogen sulfide). The hydrogen sulfide content was positive correlation with visceral pain score in patients with IBS. Consistently, NCI increased Clostridiales frequency and hydrogen sulfide content in feces of adult rats. Notably, the concentration of FA was markedly decreased in peripheral blood of IBS patients compared with non-IBS human subjects. FA supplement alleviated chronic visceral pain and normalized the Clostridiales frequency in NCI rats. In addition, FA supplement significantly reduced the frequency of sEPSCs of neurons in the spinal dorsal horn of NCI rats. Folic Acid treatment attenuated chronic visceral pain of NCI rats through reducing hydrogen sulfide production from Clostridiales in intestine. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin glycation index (HGI), which is calculated by blood glucose and hemoglobin A1c(HbA1c), reflects the individual discrepancy in HbA1c. This study aimed to investigate the association between HGI/HbA1c and serum uric acid(SUA) stratified by sex and diabetes. Methods: The study recruited 33772 participants who underwent physical examinations between April 2016 and August 2021 in Beijing Chao-Yang Hospital. A random subsample of 3000 subjects was utilized to calculate the formula of HGI and data of the remaining 30772 participants were used for analysis. HGI and HbA1c were categorized according to quartiles (Q1, Q2, Q3, Q4), using Q1 as the reference. We used multiple linear regression and restricted cubic splines for data analysis. Results: 30772 participants with a mean age of 44.4 years old were included in the analysis, 48.6% (N = 14944) of which were female and 7.7% (N = 2363) with diabetes. Associations of HGI, HbA1c and SUA were modified by sex and diabetes. The relationship between SUA levels and HGI was positive in women without diabetes, with one unit increase in HGI associating with an 11.3 μmol/L increase in SUA (P < 0.001) after adjusting for other confounders. On average, each one-unit increase in HbA1c was associated with a 14.3 μmol/L decrease in SUA in women with diabetes, a 14.9 μmol/L decrease in SUA in men with diabetes, and a 16.5 μmol/L increase in SUA in women without diabetes (all P < 0.001). The SUA levels in men without diabetes showed a bell-shaped relation with HbA1c, increasing as the HbA1c rose to around 5.7% and then falling with a further increase of HbA1c (P < 0.001). Conclusions: SUA levels were inversely correlated with HbA1c in diabetic patients, also in men with prediabetes (HbA1c ≥ 5.7%), but positively correlated with HbA1c and HGI in women without diabetes. Glycemic control may help to reduce the risk of hyperuricemia in non-diabetes women. [ABSTRACT FROM AUTHOR]

Type-2 diabetes mellitus (T2DM) is a medical condition in which oral medications avail to patients to curb their hyperglycaemia after failed dietary therapy. However, individual responses to the prescribed pharmacotherapy may differ due to their clinical profiles, comorbidities, lifestyles and medical adherence. One approach is to identify similar patients within the same community to predict their likely response to the prescribed diabetes medications. This study aims to present an evidence-based diabetes medication recommendation system (DMRS) underpinned by patient similarity analytics. The DMRS was developed using 10-year electronic health records of 54,933 adult patients with T2DM from six primary care clinics in Singapore. Multiple clinical variables including patient demographics, comorbidities, laboratory test results, existing medications, and trajectory patterns of haemoglobin A1c (HbA1c) were used to identify similar patients. The DMRS was evaluated on four groups of patients with comorbidities such as hyperlipidaemia (HLD) and hypertension (HTN). Recommendations were assessed using hit ratio which represents the percentage of patients with at least one recommended sets of medication matches exactly the diabetes prescriptions in both the type and dosage. Recall, precision, and mean reciprocal ranking of the recommendation against the diabetes prescriptions in the EHR records were also computed. Evaluation against the EHR prescriptions revealed that the DMRS recommendations can achieve hit ratio of 81% for diabetes patients with no comorbidity, 84% for those with HLD, 78% for those with HTN, and 75% for those with both HLD and HTN. By considering patients' clinical profiles and their trajectory patterns of HbA1c, the DMRS can provide an individualized recommendation that resembles the actual prescribed medication and dosage. Such a system is useful as a shared decision-making tool to assist clinicians in selecting the appropriate medications for patients with T2DM. [ABSTRACT FROM AUTHOR]

Ketamine is a noncompetitive antagonist of N -methyl-D-aspartate receptors (NMDARs). We have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms in mice. However, the detailed metabolic profile changes in the progression of ketamine-induced schizophrenia-like symptoms are still not fully elucidated. In this study, an ultra-performance liquid chromatography-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry-based untargeted hippocampus high-throughput metabolomics method was first performed to screen for potential biomarkers in a schizophrenia-like state in a chronically administered ketamine-induced mouse model. Our results identified that the amino acid and energy metabolism pathways were significantly affected in mouse models of ketamine-induced schizophrenia. The detailed amino acid profiles were subsequently quantified in the hippocampus. The results showed that ketamine dramatically decreased the Lys, Gly, and Ser levels while significantly increasing the Gln level and relative Glu-to-GABA ratio. Our study suggested that Gln, Gly and Ser metabolism disturbances might be involved in ketamine-induced schizophrenia-like phenotypes. This research offers a fresh viewpoint for creating new neuroleptic medications and contributes to understanding the mechanisms underlying ketamine-induced schizophrenia. • Ketamine-induced experimental schizophrenia can alter the amounts of a variety of metabolites in the hippocampus. • Changed metabolites mainly involved amino acids and enriched in synaptic signaling and amino acid metabolism pathway. • Gln, Gly and Ser may be potential biomarkers for ketamine-induced schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, where pre-polarized cells can maintain specific functions on the scaffold. This work examined four typical biodegradable hydrogels as supports for hESC-RPE growth. Methods: Four biodegradable hydrogels were examined: gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), alginate, and fibrin hydrogels. ARPE-19 and hESC-RPE cells were seeded onto the hydrogels separately, and the ability of these supports to facilitate adherence, proliferation, and homogeneous distribution of differentiated hESC-RPE cells was investigated. Furthermore, the hydrogel's subretinal bio-compatibility was assessed in vivo. Results: We showed that ARPE-19 and hESC-RPE cells adhered and proliferated only on the fibrin support. The monolayer formed when cells reached confluency, demonstrating the polygonal semblance, and revealing actin filaments that moved along the cytoplasm. The expression of tight junction proteins at cell interfaces on the 14th day of seeding demonstrated the barrier function of epithelial cells on polymeric surfaces and the interaction between cells. Moreover, the expression of proteins crucial for retinal functions and matrix production was positively affected by fibrin, with an increment of PEDF. Our in vivo investigation with fibrin hydrogels revealed high short-term subretinal biocompatibility. Conclusions: The research of stem cell-based cell therapy for retinal degenerative diseases is more complicated than that of cell lines. Our results showed that fibrin is a suitable scaffold for hESC-RPE transplantation, which could be a new grafting material for tissue engineering RPE cells. [ABSTRACT FROM AUTHOR]

Previously, 36 TEAM benchmark problems have been established, used to verify the numerical calculation methods of electromagnetic fields. Among them, there is only one problem related to the magnetic field considering magnetic hysteresis, which is problem 32. The results of it are obtained by experimental measurement. In this paper, a same kind of benchmark problem is proposed, in which the field results are obtained by using analytical method. This benchmark problem can be used to verify both 2D and 3D numerical calculation methods. The analytical solving process of the problem is that H is obtained by using Ampere's law, then B is calculated based on the hysteresis model of the material, so that the field distribution results are formed. The required hysteresis model could be any kind, such as Preisach model, J–A model, etc. As long as the same kind of model is used both in the benchmark problem and in the numerical method, the numerical method can be verified through the proposed benchmark problem. Considering the form of J–A hysteresis model required by the benchmark problem does not exist, which is the field separation-based forward dynamic J–A model, it is derived based on the forward static J–A model. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks (MOFs) have attracted considerable attention in numerous applications due to their large surface areas, tunable pore size, and chemical versatility. However, the performance of most MOFs and their related derivatives in applications are still hindered due to their unoptimized form. Hierarchical nano‐micromacropore MOF structure constructed by 3D printing has been shown to guide working species transportation routes, accelerates ion transportation, and increases the accessible area of MOF, thus leading to improved kinetics and enhanced application performances. Nevertheless, there is a lack of a review on 3D‐printed MOFs and their applications that summarizes and promotes this field's progress. This review first introduces the progress of preparing and embedding MOF into structures via 1) MOF coating processes, 2) in situ growth of MOFs, and 3) using presynthesized MOFs to tune the nano‐ and microstructure of MOF. Subsequently, based on various 3D printing technologies, the principles behind various feedstock material preparation and their related printing processes are discussed with respect to the macrostructure. Thereafter, the advances and recent progress of various devices by 3D‐printed MOFs are summarized with detailed analyses and discussion. Finally, an outlook in this promising field is proposed to provide a progression route for 3D‐printed MOFs. [ABSTRACT FROM AUTHOR]

EDIL3 is a strong and highly accurate diagnostic marker for breast cancer, meanwhile, EDIL3 overexpressed exosomes are novel biomarkers for the early diagnosis of triple-negative breast cancer (TNBC). Here, we proposed a fluorescent detection method for EDIL3 overexpressed exosomes, which is simple and sensitive. Basically, we utilized a magnetic nanospheres (MNS) based liquid sandwich immunoassay strategy. MNS were modified with CD63 aptamers, which can immunologically bound to the CD63 protein on the surface of exosomes. Alexa Fluor 647 labeled anti-EDIL3 antibodies (Anti-EDIL3/AF647) were used as the fluorescent probes to recognize the EDIL3 on exosomes derived from a TNBC cell line (MDA-MB-231). With the target TNBC exosomes present, sandwich structures containing MNS, exosomes and fluorescent probes were formed. After magnetic purification, optical super resolution imaging of the products was conducted to check the specificity of the assay. In addition, fluorescence signals of the products were detected to quantitatively analyze the EDIL3 overexpressed exosomes. The linear range was found to be 7.78 Ă— 101 to 7.78Ă— 106 particles ÎĽ lâˆ'1. The detection limit was approximately 10 particles ÎĽ lâˆ'1. The feasibility of the method for the detection of exosomes in complex biological samples was also demonstrated. Such a simple and sensitive detection method for EDIL3 overexpressed exosomes holds a great potential in clinical diagnosis of TNBC. [ABSTRACT FROM AUTHOR]

Background: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty.Methods: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models.Results: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development.Conclusions: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: The number of diabetic patients worldwide continues to increase. Diabetes mellitus (DM) has become one of the three chronic diseases threatening human health. Mangiferin is a kind of xanthone with multiple biological activities. Studies have confirmed that it has good activity in treating DM. Objectives: The purpose of our study was to investigate the targets and mechanism of mangiferin in the treatment of DM and to analyze its metabolites in vivo. Materials and Methods: We predict the targets and mechanism of mangiferin in DM in view of network pharmacology (NP). Mangiferin's targets were completed using Gene Cards, Swiss Target Prediction, and TCMSP database. DisGeNET database retrieved DM-related targets. The common targets were put into STRING platform to construct a protein–protein interaction (PPI) network model. DAVID platform and Cytoscape were used to achieve GO analysis and KEGG signal pathway enrichment analysis. Then, in metabolites study, LC-MS/MS was used to analyze the metabolites of mangiferin in plasma collected from SD rats. Results: A total of 37 targets for the coaction of mangiferin and DM were screened. Tumor necrosis factor (TNF), epidermal growth factor (EGF), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), hypoxia-inducible factor-1 alpha (HIF1A), nuclear factor-κB p65 (RELA), protein kinase C alpha (PRKCA), and Interleukin-2 (IL2) were selected as the most important targets. The biological functions related to DM were mainly enriched in the signaling pathway in phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kappa B), hypoxia inducible factor-1 (HiF-1), and mammalian target of rapamycin (mTOR). With reference to the obtained accurate relative molecular mass, chromatographic retention behavior, and characteristic fragment ions, a total of six metabolites including the original drug were analyzed and identified. Conclusion: This study provides key data for the mechanism of action and targets research on mangiferin, and it provides a basis for its further development into hypoglycemic drugs. [ABSTRACT FROM AUTHOR]

In-situ irradiation transmission electron microscopy (TEM) offers unique insights into the millisecond-timescale post-cascade process, such as the lifetime and thermal stability of defect clusters, vital to the mechanistic understanding of irradiation damage in nuclear materials. Converting in-situ irradiation TEM video data into meaningful information on defect cluster dynamic properties (e.g., lifetime) has become the major technical bottleneck. Here, we present a solution called the DefectTrack, the first dedicated deep learning-based one-shot multi-object tracking (MOT) model capable of tracking cascade-induced defect clusters in in-situ TEM videos in real-time. DefectTrack has achieved a Multi-Object Tracking Accuracy (MOTA) of 66.43% and a Mostly Tracked (MT) of 67.81% on the test set, which are comparable to state-of-the-art MOT algorithms. We discuss the MOT framework, model selection, training, and evaluation strategies for in-situ TEM applications. Further, we compare the DefectTrack with four human experts in quantifying defect cluster lifetime distributions using statistical tests and discuss the relationship between the material science domain metrics and MOT metrics. Our statistical evaluations on the defect lifetime distribution suggest that the DefectTrack outperforms human experts in accuracy and speed. [ABSTRACT FROM AUTHOR]

Purpose. Microwave ablation (MWA) is a minimally invasive method for the thermal ablation of benign thyroid nodules and papillary thyroid cancer (PTC) and has shown promising results. The aim of this study was to investigate the impact of MWA on thyroid antibodies and associated influencing factors. Materials and Methods. A total of 119 patients, including 69 with benign thyroid nodules and 50 with PTC, underwent MWA between June 2019 and June 2021. The serum levels of (free) triiodothyronine, (free) thyroxine, thyrotropin, and antibodies against Tg (TGAb), thyrotropin receptors (TRAb), and thyroid peroxidase (TPOAb) were measured during the follow up. Results. One month after ablation, three patients (4.3%) in the benign group had hypothyroidism, and one (1.4%) had hyperthyroidism. Four patients (5.8%) had subclinical hypothyroidism, and two (2.9%) had subclinical hyperthyroidism. Among the PTC patients, two (4%) had hypothyroidism, and one (2%) had hyperthyroidism. Two patients (4%) had subclinical hypothyroidism, and one (2%) had subclinical hyperthyroidism. In the benign group, among patients with normal preablation antibodies, the postablation TGAb abnormal rate was 12.7%, the TPOAb level was 4.8%, and the TRAb level was 0%. Among PTC patients, the postablation TGAb abnormal rate was 11.4%, the TPOAb level was 8.7%, and the TRAb level was 4.0%. The cutoff value of preablation TGAb for predicting postoperative antibody abnormalities was 19.0 IU/mL, while that of TPOAb was 11.4 IU/mL. Conclusions. MWA of thyroid nodules had little influence on thyroid function and antibodies. Elevations in TGAb, TPOAb, and TRAb beyond the normal ranges after MWA may be related to high preablation levels of TGAb and TPOAb. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcomes between microwave ablation (MWA) and parathyroidectomy (PTX) for the treatment of primary hyperparathyroidism (pHPT). Materials and methods: This retrospective study enrolled 212 patients with pHPT treated by either MWA (MWA group) or PTX (PTX group) from January 2015 to October 2020. The baseline data were balanced through propensity score matching. Clinical cure was evaluated by the Kaplan-Meier method and compared between the MWA and PTX groups. The risk factors related to persistent or recurrent pHPT were screening out using a Cox proportional hazards regression model. Results: After propensity score matching, a total of 174 patients were enrolled in the present study, with 87 patients in each group. During the follow-up period (median, 28.5 months), there were no differences between the two groups regarding the clinical cure (hazard ratio, 1.71; 95% confidence interval: 0.81-3.62; p =.155), persistent pHPT rate (13.8% vs. 10.3%, p =.643), recurrent pHPT rate (6.9% vs. 3.4%, p =.496), or major complications (6.9% vs. 3.4%, p =.496). MWA resulted in a shorter procedure time (30 min vs. 60 min), smaller incision length (0.1 cm vs. 7 cm) and slightly higher costs (25745 CNY vs. 24111 CNY) (all p <.001). High levels of preoperative intact parathyroid hormone (p =.01) and multiple pHPT nodules (p <.001) were independent risk factors for recurrent and persistent pHPT in the two groups. Conclusion: MWA and PTX have comparable clinical outcomes for pHPT. MWA has a shorter procedure time and smaller incision length. Key Points: • There were no differences in terms of clinical cure, persistent pHPT, recurrent pHPT, or major complications between MWA and PTX in the treatment of pHPT. • MWA is minimally invasive and results in a shorter procedure time. • Multiple nodules and high levels of iPTH were the independent risk factors for recurrent and persistent pHPT. [ABSTRACT FROM AUTHOR]