Search

This study discusses implementing the Child Friendly School program based on ethnopedagogy concepts in Gorontalo Regency. A descriptive qualitative approach was used through research at MTs Negeri 1 Telaga Biru, SMP Negeri 1 Limboto, and SMA Negeri 1 Telaga. The subjects of the study involved the entire school community directly involved in the program's implementation. Purposive sampling techniques are used to determine research subjects according to the objectives of this study. Data collection instruments consist of interviews, observations, and documentation. The study results show that Ethno pedagogy in the Child-Friendly School Program is integrated into various school activities, such as integrated activities, literacy and environmental management, that refer to Gorontalo's local values and culture. However, there are obstacles and challenges related to school-institution collaboration, school infrastructure renewal, program funding, cultural facilities, geographical location, and foreign cultural influences. This finding is expected to be a reference for other educational institutions in implementing the Child-Friendly School Program and as an evaluation for the three institutions studied to improve and improve the process of implementing this program.

Weld seam detection is particularly crucial within industrial systems, as it promptly reflects the quality of product fabrication and performance, ensuring the final metallurgical product's quality while mitigating potential losses stemming from product quality issues. This paper proposed the InfoFPN Cross Refinement Network (InfoCRNet) for the weld seam detection, achieving an accuracy rate of 98,90% and F1 score of 98,85 %. [ABSTRACT FROM AUTHOR]

The 19F(p, αγ)16O reaction is of crucial importance for Galactic 19F abundances and CNO cycle loss in first generation Population III stars. Due to its extremely small cross sections, the 19F(p, αγ)16O reaction has not been measured in the low energy part of the Gamow window(70-200 keV). As a day-one campaign, the experiment was performed under the extremely low cosmicray-induced background environment of the China JinPing Underground Laboratory(CJPL), one of the deepest underground laboratories in the world. The γ-ray yields were measured over Ec.m. =72.4–344 keV, covering the full Gamow window for the first time. The direct experimental data will help people to expound the fluorine over-abundances, energy generation, as well as heavy-element nuclosynthesis scenario in asymptotic giant branch (AGB) stars, with the astrophysical model on the firm ground.

JUNA measured the SP 19 sp F(p, ) SP 16 sp O channel down to the lowest energy of E SB c.m. sb 72 keV, and the JUNA rate deviates significantly from the previous expectations by a factor of 0.2-1.3 [[21]]. Thanks to the advantages provided by CJPL, the Jinping Underground Nuclear Astrophysics (JUNA) experiment collaboration has proposed to exploit the extremely low background and try to reach the Gamow region in CJPL-II A1 Hall (see Figure 1) [[9]]. Previously, this reaction was thought to be weak compared to the SP 19 sp F(p, ) SP 16 sp O reaction, so most of the SP 19 sp F produced by the CNO cycle would be recycled back into SP 16 sp O, with no substantial chemical abundance changes. The background mainly consists of the neutron-induced background from SP 13 sp C( ,n) SP 16 sp O reaction and the gamma background from other ( , ) reactions, making the analysis complicated. [Extracted from the article]

Rechargeable Li-O 2 batteries (LOBs) are considered as one of the most promising candidates for new-generation energy storage devices. One of major impediments is the poor cycle stability derived from the sluggish reaction kinetics of unreliable cathode catalysts, hindering the commercial application of LOBs. Therefore, the rational design of efficient and durable catalysts is critical for LOBs. Optimizing surface electron structure via the negative shift of the d-band center offers a reasonable descriptor for enhancing the electrocatalytic activity. In this study, the construction of Ni-incorporating RuO 2 porous nanospheres is proposed as the cathode catalyst to demonstrate the hypothesis. Density functional theory calculations reveal that the introduction of Ni atoms can effectively modulate the surface electron structure of RuO 2 and the adsorption capacities of oxygen-containing intermediates, accelerating charge transfer between them and optimizing the growth pathway of discharge products. Resultantly, the LOBs exhibit a large discharge specific capacity of 19658 mA h g -1 at 200 mA g -1 and extraordinary cycle life of 791 cycles. This study confers the concept of d-band center modulation for efficient and durable cathode catalysts of LOBs., (© 2024 Wiley‐VCH GmbH.)

Background: There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment., Methods: This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC). Amino acid targets were 2.0 g/kg per day in the AAS group and 1.2 g/kg per day in the SC group. The AAS group received additional amino acids intravenously, while the SC group received an iso-energetic 5% glucose intravenously., Results: Overall, 407 patients (AAS group, 204; SC group, 203) were included in this study. During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs. 25.16 kcal/kg per day, P=0.493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than that in the SC group (1.81 vs. 0.94 g/kg per day, P<0.001). The infection incidence during hospitalization and that within 30 days of surgery was significantly lower in the AAS group than that in the SC group (P=0.031 and P=0.024, respectively). The 30-day postoperative incidence of amino acid treatment-related adverse events and other complications did not significantly differ between the two groups. The postoperative hospital stay was significantly different between the two groups (P<0.001)., Conclusions: AAS was associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Although natural attenuation is an economic remediation strategy for uranium (U) contamination, the role of organic molecules in driving U natural attenuation in postmining aquifers is not well-understood. Groundwaters were sampled to investigate the chemical, isotopic, and dissolved organic matter (DOM) compositions and their relationships to U natural attenuation from production wells and postmining wells in a typical U deposit (the Qianjiadian U deposit) mined by neutral in situ leaching. Results showed that Fe(II) concentrations and δ 34 S SO4 and δ 18 O SO4 values increased, but U concentrations decreased significantly from production wells to postmining wells, indicating that Fe(III) reduction and sulfate reduction were the predominant processes contributing to U natural attenuation. Microbial humic-like and protein-like components mediated the reduction of Fe(III) and sulfate, respectively. Organic molecules with H/C > 1.5 were conducive to microbe-mediated reduction of Fe(III) and sulfate and facilitated the natural attenuation of dissolved U. The average U attenuation rate was -1.07 mg/L/yr, with which the U-contaminated groundwater would be naturally attenuated in approximately 11.2 years. The study highlights the specific organic molecules regulating the natural attenuation of groundwater U via the reduction of Fe(III) and sulfate.

Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Seepage of uranium tailings has become a focus of attention in the uranium mining and metallurgy industry, and in-situ microbial remediation is considered an effective way to treat uranium pollution. However, this method has the drawbacks of easy biomass loss and unstable remediation effect. To overcome these issues, spare red soil around the uranium mine was used to enhance the efficiency and stability of bioremediation. Furthermore, the bioremediation mechanism was revealed by employing XRD, FTIR, XPS, and 16S rRNA. The results showed that red soil, as a barrier material, had the adsorption potential of 8.21-148.00 mg U/kg soil, but the adsorption is accompanied by the release of certain acidic and oxidative substances. During the dynamic microbial remediation, red soil was used as a cover material to neutralize acidity, provide a higher reduction potential (<-200 mV), and increase the retention rate of microbial agent (19.06 mL/d) compared to the remediation group without red soil. In the presence of red soil, the anaerobic system could maintain the uranium concentration in the solution below 0.3 mg/L for more than 70 days. Moreover, the generation of new clay minerals driven by microorganisms was more conducive to the stability of uranium tailings. Through alcohol and amino acid metabolism of microorganisms, a reducing environment with reduced valence states of multiple elements (such as S 2- , Fe 2+ , and U 4+ ) was formed. At the same time, the relative abundance of functional microbial communities in uranium tailings improved in presence of red soil and Desulfovirobo, Desulfocapsa, Desulfosporosinus, and other active microbial communities reconstructed the anaerobic environment. The study provides a new two-in-one solution for treatment of uranium tailings and resource utilization of red soil through in-situ microbial remediation., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recently, there has been a growing interest in using sustainable energy to decrease lignin monomers to generate high-value-added products. Here, we present a protocol for electrocatalytic hydrogenation of 5-hydroxymethylfurfural. We describe steps for catalyst preparation, performing electrocatalytic experiments, high-performance liquid chromatography analysis, and in situ infrared reflection-absorption spectroscopy testing. The synthesized catalyst used in this reaction exhibits enhanced selectivity and Faradaic efficiency in NaClO 4 solution. For complete details on the use and execution of this protocol, please refer to Zhang et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems.

As a key executioner of pyroptosis, Gasdermin D (GSDMD) plays a crucial role in host defense and emerges as an essential therapeutic target in the treatment of inflammatory diseases. So far, the understanding of the mechanisms that regulate the protein level of GSDMD to prevent detrimental effects and maintain homeostasis is currently limited. Here, we unveil that ubiquitin-specific peptidase 18 (USP18) works as a negative regulator of pyroptosis by targeting GSDMD for degradation and preventing excessive innate immune responses. Mechanically, USP18 recruits E3 ubiquitin ligase mind bomb homolog 2 (MIB2) to catalyze ubiquitination on GSDMD at lysine (K) 168, which acts as a recognition signal for the selective autophagic degradation of GSDMD. We further confirm the alleviating effect of USP18 on LPS-triggered inflammation in vivo. Collectively, our study demonstrates the role of USP18 in regulating GSDMD-mediated pyroptosis and reveals a previously unknown mechanism by which GSDMD protein level is rigorously controlled by selective autophagy., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Liqiu Wang et al.)

Background: Calcium channel blockers (CCBs) are widely used in the clinical management of hypertension. Depression, a common comorbidity of hypertension, is an important issue in the management of hypertension. However, the impact of CCBs on depression risk remains controversial. We aim to investigate the causal effect of CCBs on depression through drug-target Mendelian randomization (MR) analysis., Methods: To proxy CCBs, we utilized the genetic variations located in or around drug target genes that were related to systolic blood pressure (SBP). Coronary artery disease (CAD) served as the positive control outcome. Genetic summary data of SBP, CAD, and depression were obtained from genome-wide association studies (GWAS) based on European population. Inverse variance weighted (IVW) method was applied as the main analysis to estimate the causal effect. Cochran's Q test, MR-Egger intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) and leave-one-out sensitivity analysis were used to test the robustness of the results. Meta-analysis was applied to further confirm whether causal relationships existed between CCBs and depression., Results: The IVW results failed to reveal any causal relationship between genetic proxies for CCBs and depression ( P > 0.05). Cochran's Q test showed no evidence of heterogeneity ( P > 0.05). The MR-Egger intercept test suggested no evidence of directional pleiotropy, and the MR pleiotropy residual sum and outlier (MR-PRESSO) global test for horizontal pleiotropy was also not significant ( P > 0.05). Leave-one-out analysis did not reveal any genetic variant that influenced the results. In addition, the meta-analysis further confirmed the absence of a causal relationship., Conclusion: The present study indicates no association of genetic proxies for CCBs with depression. Further studies are necessary to provide definitive evidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, Wang, Wang, Lian and Xie.)

Pulmonary arterial hypertension (PAH) was a devastating disease characterized by artery remodeling, ultimately resulting in right heart failure. The aim of this study was to investigate the effects of canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i) with mild SGLT1 inhibitory effects, on rats with PAH, as well as its direct impact on pulmonary arterial smooth muscle cells (PASMCs). PAH rats were induced by injection of monocrotaline (MCT) (40 mg/kg), followed by four weeks of treatment with CANA (30 mg/kg/day) or saline alone. Pulmonary artery and right ventricular (RV) remodeling and dysfunction in PAH were alleviated with CANA, as assessed by echocardiography. Hemodynamic parameters and structural of pulmonary arteriole, including vascular wall thickness and wall area, were reduced by CANA. RV hypertrophy index, cardiomyocyte hypertrophy, and fibrosis were decreased with CANA treatment. PASMCs proliferation was inhibited by CANA under stimulation by platelet-derived growth factor (PDGF)-BB or hypoxia. Activation of AMP kinase (AMPK) was induced by CANA treatment in cultured PASMCs in a time- and concentration-dependent manner. These effects of CANA were attenuated when treatment with compound C, an AMPK inhibitor. Abundant expression of SGLT1 was observed in PASMCs and pulmonary arteries, while SGLT2 expression was undetectable. SGLT1 increased in response to PDGF-BB or hypoxia stimulation, while PASMCs proliferation was inhibited and beneficial effects of CANA were counteracted by knockdown of SGLT1. Our research demonstrated for the first time that CANA inhibited the proliferation of PASMCs by regulating SGLT1/AMPK signaling and thus exerted an anti-proliferative effect on MCT-induced PAH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Glycolytic metabolism is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and tumor-associated stromal cells play important roles in tumor metabolism. We previously reported that tumor-associated macrophages (TAMs) facilitate PDAC progression. However, little is known about whether TAMs are involved in regulating glycolysis in PDAC. Here, we found a positive correlation between CD68 + TAM infiltration and FDG maximal standardized uptake (FDG SUVmax) on PET-CT images of PDAC. We discovered that the glycolytic gene set was prominently enriched in the high TAM infiltration group through Gene Set Enrichment Analysis using The Cancer Genome Atlas database. Mechanistically, TAMs secreted IL-8 to promote GLUT3 expression in PDAC cells, enhancing tumor glycolysis both in vitro and in vivo, whereas this effect could be blocked by the IL-8 receptor inhibitor reparixin. Furthermore, IL-8 promoted the translocation of phosphorylated STAT3 into the nucleus to activate the GLUT3 promoter. Overall, we demonstrated that TAMs boosted PDAC cell glycolysis through the IL-8/STAT3/GLUT3 signaling pathway. Our cumulative findings suggest that the abrogation of TAM-induced tumor glycolysis by reparixin might exhibit an antitumor impact and offer a potential therapeutic target for PDAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Communication skills (CS) represent a core competency in radiology residency training. However, no structured curriculum exists to train radiology residents in CS in China. The aim of this study was to evaluate the status and prevalence of doctor-patient communication training among radiology residents in nine Chinese accredited radiology residency training programs and to determine whether there is a perceived need for a formalized curriculum in this field., Methods: We administered a cross-sectional online survey to radiology residents involved in CS training at nine standard residency training programs in China. The questionnaire developed for this study included CS training status, residents' demographics, attitudes toward CS training, communication needs, and barriers. Residents' attitudes toward CS training were measured with the Communication Skills Attitude Scale (CSAS) and its subscales, a positive attitude scale (PAS) and negative attitude scale (NAS)., Results: A total of 133 (48.36%) residents participated in the survey. The mean total scores on the two dimensions of the CSAS were 47.61 ± 9.35 in the PAS and 36.34 ± 7.75 in the NAS. Factors found to be significantly associated with the PAS included receiving previous training in CS, medical ethics, or humanities and the doctor's attire. We found that first-year residents and poor personal CS were the most influential factors on the NAS. Only 58.65% of participants reported having previously received CS training during medical school, and 72.93% of respondents reported failure in at least one difficult communication during their residency rotation. Most of those surveyed agreed that CS can be learned through courses and were interested in CS training. Some of the most common barriers to implementing formal CS training were a lack of time, no standardized curriculum, and a lack of materials and faculty expertise., Conclusions: Most residents had a very positive attitude toward CS training and would value further training, despite the limited formal CS training for radiology residents in China. Future efforts should be made to establish and promote a standard and targeted CS curriculum for Chinese radiology residents., (© 2024. The Author(s).)

Background & Aims: While obesity has been reported as a protective factor in septic patients, little is known about the potential modifying effects of age and sex. The objective of this study is to investigate age and sex-specific associations between obesity and the prognosis of septic patients., Methods: A retrospective analysis was conducted on a cohort of 15,464 septic patients, categorized by body mass index (BMI) into four groups: underweight (<18.5 kg/m 2 , n = 483), normal (18.5-24.9 kg/m 2 , n = 4344), overweight (25-29.9 kg/m 2 , n = 4949) and obese (≥30 kg/m 2 , n = 5688). Multivariable logistic regression and inverse probability weighting were employed to robustly confirm the protective effect of a higher BMI on 28-day mortality, with normal weight serving as the reference category. Subgroup analyses based on age (young: 18-39, middle-aged: 40-64 and elderly: ≥65) and sex were performed., Results: The findings demonstrate that high BMI independently confers a protective effect against 28-day mortality in septic patients. However, the relationship between BMI and 28-day mortality exhibits a non-linear trend, with a BMI of 34.5 kg/m 2 displaying the lowest odds ratio. Notably, the survival benefits associated with a high BMI were not observed in the young group. Moreover, being underweight emerges as an independent risk factor for middle-aged and elderly female patients, while in males it is only a risk factor in the elderly group. Interestingly, being overweight and obese were identified as independent protective factors in middle-aged and elderly male patients, but not in females., Conclusions: The effect of BMI on mortality in septic patients varies according to age and sex. Elderly individuals with sepsis may derive more prognostic benefits from obesity., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study investigates in silico the contribution of the hair follicle to the overall dermal permeability of small molecules, as published experimental work provides inconclusive information on whether the follicular route favours the permeation of hydrophobic or hydrophilic permeants., Method: A study is conducted varying physico-chemical parameters of permeants such as lipophilicity, molecular weight and protein binding. The simulated data is compared to published experimental data to discuss how those properties can modulate the contribution of the hair follicle to the overall dermal permeation., Results: The results indicate that the contribution of the follicular route to dermal permeation can range from negligible to notable depending on the combination of lipophilic/hydrophilic properties of the substance filling the follicular route and the permeant., Conclusion: Characterisation of the substance filling the follicular route is required for analysing the experimental data of dermal permeation of small molecules, as changes between in vivo and in vitro due to handling of samples and cessation of vital functions can modify the contribution of the follicular route to overall dermal permeation, hence hindering data interpretation., (© 2024. The Author(s).)

Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-Seq of patient-matched colon and ileum biopsies from treatment-naive pediatric patients with CD (n = 169) and a control cohort (n = 108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein gene Pmp22 and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we found that pediatric patients with CD with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels of PMP22. These findings strongly indicate that miR-29 upregulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation., (© 2024. The Author(s).)

Pediatric Crohn's disease (CD) is characterized by a severe disease course with frequent complications. We sought to apply machine learning-based models to predict risk of developing future complications in pediatric CD using ileal and colonic gene expression. Gene expression data was generated from 101 formalin-fixed, paraffin-embedded (FFPE) ileal and colonic biopsies obtained from treatment-naïve CD patients and controls. Clinical outcomes including development of strictures or fistulas and progression to surgery were analyzed using differential expression and modeled using machine learning. Differential expression analysis revealed downregulation of pathways related to inflammation and extra-cellular matrix production in patients with strictures. Machine learning-based models were able to incorporate colonic gene expression and clinical characteristics to predict outcomes with high accuracy. Models showed an area under the receiver operating characteristic curve (AUROC) of 0.84 for strictures, 0.83 for remission, and 0.75 for surgery. Genes with potential prognostic importance for strictures (REG1A, MMP3, and DUOX2) were not identified in single gene differential analysis but were found to have strong contributions to predictive models. Our findings in FFPE tissue support the importance of colonic gene expression and the potential for machine learning-based models in predicting outcomes for pediatric CD., (© 2024. The Author(s).)

Comprehensive analysis of multi-omics data can reveal alterations in regulatory pathways induced by cellular exposure to chemicals by characterizing biological processes at the molecular level. Data-driven omics analysis, conducted in a dose-dependent or dynamic manner, can facilitate comprehending toxicity mechanisms. This study introduces a novel multi-omics data analysis designed to concurrently examine dose-dependent and temporal patterns of cellular responses to chemical perturbations. This analysis, encompassing preliminary exploration, pattern deconstruction, and network reconstruction of multi-omics data, provides a comprehensive perspective on the dynamic behaviors of cells exposed to varying levels of chemical stimuli. Importantly, this analysis is adaptable to any number of omics layers, including site-specific phosphoproteomics. We implemented this analysis on multi-omics data obtained from HepG2 cells exposed to a range of caffeine doses over varying durations and identified six response patterns, along with their associated biomolecules and pathways. Our study demonstrates the effectiveness of the proposed multi-omics data analysis in capturing multidimensional patterns of cellular response to chemical perturbation, enhancing understanding of pathway regulation for chemical risk assessment.

Lane detection under extreme conditions presents a highly challenging task that requires capturing each crucial pixel to predict the complex topology of lane lines and differentiate the various lane types. Existing methods predominantly rely on deep feature extraction networks with substantial parameters or the fusion of multiple prediction modules, resulting in large model sizes, embedding difficulties, and slow detection speeds. This article proposes a Proportional Feature Pyramid Network (P-FPN) through fusing the weights into the FPN for lane detection. For obtaining a more accurately detecting result, the cross refinement block is introduced in the P-FPN network. The cross refinement block takes the feature maps and anchors as inputs and gradually refines the anchors from high to low level feature maps. In our method, the high-level features are explored to predict lanes coarsely while local-detailed features are leveraged to improve localization accuracy. Extensive experiments on two widely used lane detection datasets, The Chinese Urban Scene Benchmark for Lane Detection (CULane) and the TuSimple Lane Detection Challenge (TuSimple) datasets, demonstrate that the proposed method achieves competitive results compared with several state-of-the-art approaches., Competing Interests: The authors declare there are no competing interests., (©2024 Hui et al.)

Steel hydrochloric acid pickling sludge (SHPS), containing the heavy metals Fe, Zn, and Ni and a high chloride salt content, is considered a hazardous solid waste. With the gradual reduction of high-grade metal mineral resources such as Fe, Zn and Ni, it is particularly urgent to recycle valuable metals such as Fe, Zn and Ni in solid waste SHPS in order to realize the resource utilization of SHPS and reduce the environmental harm caused by SHPS. In addition, SHPS usually contains different amounts of alkali chloride, which will have a serious adverse impact on the subsequent extraction and smelting process of Fe, Zn and other metals. Therefore, the removal of chloride plays an important role in the resource utilization of valuable metals in SHPS. Thus, in this study, the effects of water washing dechlorination process parameters such as liquid-solid (L/S) ratio, SHPS particle size, washing time and washing frequency on the chloride removal rate were investigated. The best experimental parameters of SHPS washing were obtained. At the same time, the microscopic morphology and crystal phase composition of SHPS before and after washing were explored. The results showed that the optimized conditions were as follows: room temperature, a L/S ratio of 3 : 1, an SHPS particle size of 100 mesh, and 10 min of water washing, repeated two or three times; under these conditions, the removal rate of Cl, Na, Ca, K, Mg, and S reached 96.64-99.68%, 97.38-99.89%, 36.40-60.37%, 49.11-54.82%, 39.18-40.22%, and 36.98-42.13% respectively. The contents of Cl, K, and Na in filter residue (FR) meets the requirements in GB/T 36144-2018 and GB/T 32545-2016. Conversely, the contents of Fe, Zn, Mn and Ni in the FR are enriched, which is more conducive to the subsequent resource utilization of SHPS. The scanning electron microscope (SEM) image shows the particle size of the FR particles is reduced after washing. The X-ray diffractometer (XRD) results proved that the chlorine salt content in the FR after washing was significantly reduced, the diffraction peaks of Al 2 O 3 appeared in the FR, and the diffraction peak intensity of CaCO 3 , Fe 2 O 3 and SiO 2 increased., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Blue-laser-diode-pumped Pr 3+ -based continuous-wave (CW) green lasers have aroused growing research interest in developing optoelectronic applications and deep ultraviolet laser sources due to their simple and compact structural design. However, the obstacle of thermally induced effects limits the available output power of Pr 3+ -based green lasers. Herein, combined with the theoretical analysis and experimental feedback, we effectively adjust the heat distribution inside the Pr 3+ :LiYF 4 gain crystal by optimizing the crystal dimension and doping concentration. The excellent mode matching between the pump and green lasers is achieved under the consideration of thermally induced effects, yielding a maximum CW output power of 7.56 W. To the best of our knowledge, this is the largest output power of Pr 3+ -based CW green lasers so far. Moreover, the obtained green laser demonstrates excellent output stability (RMS = 1.27%) and beam quality (M 2  = 1.30 × 1.12) under the lasing operation state with the maximum output power. We hope that this study can provide a feasible paradigm for developing blue-laser-diode-pumped visible lasers, especially for high-power lasers.

Ferroptosis is a recently discovered cell programmed death. Extensive researches have indicated that ferroptosis plays an essential role in tumorigenesis, development, migration and chemotherapy drugs resistance, which makes it become a new target for tumor therapy. Non-coding RNAs (ncRNAs) are considered to control a wide range of cellular processes by modulating gene expression. Recent studies have indicated that ncRNAs regulate the process of ferroptosis via various pathway to affect the development of cancer. However, the regulation network remains ambiguous. In this review, we outlined the major metabolic processes of ferroptosis and concluded the relationship between ferroptosis-related ncRNAs and cancer progression. In addition, the prospect of ncRNAs being new therapeutic targets and early diagnosis biomarkers for cancer by regulating ferroptosis were presented, and the possible obstacles were also predicted. This could help in discovering novel cancer early diagnostic methods and therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Permeability and partition coefficients of the skin barrier are important for assessing dermal absorption, bioavailability, and safety of cosmetics and medicine. We use the Potts and Guy equation to analyse the dependence of skin permeability on the hydrophobicity of permeants and highlight the significant differences in published datasets. Correlations of solute partition to skin are examined to understand the likely causes of the differences in the skin permeability datasets. Recently published permeability datasets show weak correlation and low dependence on hydrophobicity. As expected, early datasets show good correlation with hydrophobicity due to the related derivation. The weaker correlation of later datasets cannot be explained by the partition to skin lipids. All the datasets of solute partition to skin lipid showed a similar correlation to hydrophobicity where the log-linear correlation coefficient of partition is almost the same of the log-linear coefficient of Potts and Guy equation. Weak correlation and dependence of the late permeability datasets with SC lipid/water partition and that they are significantly under predicted by the Potts and Guy equation suggests either additional non-lipid pathway at play or a weaker skin barrier property., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Deacon reports financial support was provided by Biotechnology and Biological Sciences Research Council. Benjamin Deacon reports financial support was provided by Unilever Plc., (Copyright © 2023. Published by Elsevier Ltd.)