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Abstract Acne vulgaris, a prevalent chronic inflammatory skin disorder, is often characterized by hyperactive sebaceous glands and excessive sebum production, presenting a significant therapeutic challenge. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is clinically effective in treating moderate to severe acne, the molecular mechanisms underlying its therapeutic effects remain largely unexplored. In this study, we investigated the impact of ALA-PDT on lipid metabolism in an acne-like mouse model and in immortalized human sebocytes (XL-i-20), focusing on the role of the OLR1-Wnt/β-catenin pathway. We employed transcriptomic analysis, lipid staining, and gene silencing techniques to dissect the molecular interactions induced by ALA-PDT. Our findings revealed that ALA-PDT significantly reduces lipogenesis by upregulating OLR1, which in turn suppresses the SREBP1-FAS axis, thereby decreasing lipid accumulation in sebocytes. Furthermore, activation of the OLR1-Wnt/β-catenin pathway was essential for these lipogenic effects, as silencing OLR1 or activating Wnt/β-catenin signaling reversed lipogenesis inhibition. This study elucidates a novel mechanistic pathway in ALA-PDT-mediated acne treatment, highlighting OLR1 as a promising target for future therapeutic strategies.

Objective:To investigate the availability and use of child safety seats among children aged 0-3 years, so as to provide the basis for improving riding safety for children. Methods:Parents of children aged 0-3 years in Huangpu District, Shanghai Municipality, were recruited using the stratified multistage random sampling method from May to July 2024. Demographic information, family travel patterns, the use of child safety seat and related health beliefs were collected using questionnaire surveys. Factors affecting the use of child safety seats were identified using a multivariable logistic regression model. Results:Totally 514 valid questionnaires were recovered, with an effective rate of 96.98%. The respondents included 122 fathers (23.74%) and 392 mothers (76.26%), with a median age of 34.00 (interquartile range, 5.00) years. There were 446 families equipping with child safety seats, accounting for 86.77%; and 169 families using child safety seats, accounting for 32.88%. Multivariable logistic regression analysis showed that the parents who had children aged >1-2 years (OR=0.597, 95%CI: 0.366-0.973), travelled 2-4 times per month (OR=0.359, 95%CI: 0.213-0.607) or once per month or less (OR=0.384, 95%CI: 0.202-0.729), and scored high in perceived barrier (OR=0.634, 95%CI: 0.486-0.827) were less likely to use child safety seats; the parents who had children with local household registration (OR=2.506, 95%CI: 1.356-4.633), travelled 5-

Abstract Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. Mechanistically, Cdk14 ablation inhibited the proliferation of epithelial and vascular endothelial cells, inducing cell cycle arrest at the G2/M phase. Through RNA-seq analysis of both endothelial and epithelial cells, we found that knockdown of Cdk14 controls the expression of signal transducers and activator of transcription 1 (STAT1) as well as associated genes in interferon signaling. Disruption of Cdk14 interferes with IFN-γ induced lung repair in vivo, suggesting potential crosstalk of CDK14 signaling and IFN-γ pathway. Our work highlights the importance of Cdk14 in lung development and regenerative repair through an uncharacterized CDK14- IFN-γ signaling axis.

Abstract Oxidative stress plays a critical role in postmenopausal osteoporosis, yet its impact on osteoblasts remains underexplored, limiting therapeutic advances. Our study identifies phospholipid peroxidation in osteoblasts as a key feature of postmenopausal osteoporosis. Estrogen regulates the transcription of glutathione peroxidase 4 (GPX4), an enzyme crucial for reducing phospholipid peroxides in osteoblasts. The deficiency of estrogen reduces GPX4 expression and increases phospholipid peroxidation in osteoblasts. Inhibition or knockout of GPX4 impairs osteoblastogenesis, while the elimination of phospholipid peroxides rescues bone formation and mitigates osteoporosis. Mechanistically, 4-hydroxynonenal, an end-product of phospholipid peroxidation, binds to integrin-linked kinase and triggers its protein degradation, disrupting RUNX2 signaling and inhibiting osteoblastogenesis. Importantly, we identified two natural allosteric activators of GPX4, 6- and 8-Gingerols, which promote osteoblastogenesis and demonstrate anti-osteoporotic effects. Our findings highlight the detrimental role of phospholipid peroxidation in osteoblastogenesis and underscore GPX4 as a promising therapeutic target for osteoporosis treatment.

Abstract The relationship between hearing loss (HL) and Parkinson’s disease (PD) remains unclear. Using individual-level and summary-level data from the UK Biobank and the largest genome-wide association studies, we examined this link through observational, Mendelian randomization and genetic pleiotropy analyses. Among 158,229 participants, PD risk rose with HL severity especially in elder and males, and hearing aids significantly reduced PD risk in males. Although our results did not support a causal association, genetic correlation analysis suggested a localized genetic overlap (17q21.31). We identified 1545 SNPs and 63 genes with pleiotropic effects on HL and PD, including 79 novel SNPs across 6 loci, with 3 showing strong co-localization. These loci were enriched in key tissues like brain, heart, liver and pancreas, linked to the dihydrolipoyl dehydrogenase complex pathway, and targeted by drugs such as Warfarin and Phenprocoumon. Overall, this study reveals the risk association, genetic basis, and pleiotropic loci connecting HL and PD.

Background: Elevated blood pressure (BP) in childhood is associated with adult hypertension and arterial stiffness. However, the effect of long-term time in target range (TTR) for BP since childhood on the risk of arterial stiffness in midlife remains unclear. Objectives: The purpose of this study was to determine the independent association of TTR for systolic blood pressure (SBP) from childhood to midlife with arterial stiffness in adulthood. Methods: This study used data from the ongoing cohort of the Hanzhong Adolescent Hypertension Study. SBP-TTR was assessed over 36 years, with the target ranges of SBP defined as the 90th to 95th percentile of SBP for age, sex, and height in childhood, and 110 to 130 mm Hg in adulthood. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1,400 cm/s. Results: Of the total 1,959 participants, 55.5% (1,088 of 1,959) were men, and the mean age was 49 years. The risk of arterial stiffness exhibited a gradual decrease with increasing SBP-TTR over the 36-year follow-up. Compared with the participants in the lowest quartile of SBP-TTR from childhood to midlife, those in the highest quartile showed significantly reduced arterial stiffness risk in midlife. This association persisted even after adjusting for mean SBP and SBP variability. Furthermore, men in the highest quartile of SBP-TTR demonstrated a markedly lower arterial stiffness risk than those in the lowest quartile, whereas this effect was not observed in women. Conclusions: Higher long-term SBP-TTR from childhood to midlife is associated with a reduced risk of arterial stiffness in midlife, regardless of the mean SBP or SBP variability.

Icing is one of the most serious threats to power grid security in cold seasons. This article studies a problem of cooperatively scheduling inspection unmanned aerial vehicles (UAVs) and deicing UAVs for power grid deicing, the aim of which is to minimize the total expected loss of outages and collapses caused by the icing disaster. Uncertain outage risk, collapse risk, and deicing workload of each power line are modeled as fuzzy values predicted by fuzzy deep learning models, and we transform the fuzzy optimization problem into a crisp optimization problem based on fuzzy arithmetics and uncertain theory. We propose an evolutionary algorithm, which combines global search without individual interaction and adaptive local search that uses a fuzzy inference system to determine the operator to be applied on each solution. The algorithm is fully parallelizable and therefore can solve the problem very efficiently based on GPU parallel acceleration. Computational results on real-world problem instances validate the performance of the proposed method compared to the state of the arts.

Abstract Exploring sustainable alternative constituents is a key pathway to carbon-neutralization of concrete, but often limited to insufficient understandings of how they interact with conventional concrete components at microscale. In this paper we reviewed the most cutting-edge microprobes used for such purposes, from both laboratory setup to synchrotron radiation-based techniques. We also provided practical guidelines on sample preparation and result analysis, which could benefit researchers who plan to adopt these methods

Due to the impact of COVID-19, collaborative online international learning (COIL) increasingly plays an important role in the internationalization of higher education. Based on a participatory case study of a COIL program given at Shanghai University (SHU), this paper explores how students, foreign professors, and professors in China prepare, understand, and experience online teaching, learning, and assessment in a COIL program. Three findings include 1). Organizing COIL Programs with a Global Perspective; 2). Enhancing Teaching and Learning through Intercultural Communication; and 3). The Barriers of COIL in Chinese Universities. Taking insiders' perspectives, we argue that a cultural gap regarding teaching and learning styles can affect COIL programs in Chinese universities, posing challenges for both students and teachers. We suggest that program organizers should focus on the cultural gaps affecting these programs, and provide additional opportunities for intercultural communication to address the cultural gaps.

Abstract Background While many studies have reported renal involvement in sarcoidosis, there is limited description of the pathological manifestations of renal sarcoidosis (RS). This study aimed to explore the standardized pathological diagnosis of RS while evaluating the relationship among pathology, clinical manifestations, and prognosis. Methods We conducted a retrospective, single-center study of RS in renal biopsy cases treated in our department between January 2019 and December 2023. Results We identified 5 patients (4 men, 1 woman; median age 52 years, IQR 36–61 years). Two patients were diagnosed with non-caseating granulomatous interstitial nephritis (GTN), while two patients were diagnosed with tubulointerstitial nephritis without granulomas (TIN), and one patient was diagnosed with acute tubular necrosis (ATN). The grading of tubulointerstitial acute inflammation revealed 2 cases (case 4 and case 5) graded as (+++), with serum creatinine levels greater than 900 µmol/L at onset. Additionally, there were 2 cases (case 2 and case 3) gradedas (+), and 1 case (case 1)graded as (-), with serum creatinine levels approximately 400 µmol/L at onset. All 5 cases exhibited an interstitial fibrosis grade of (-). However, in the second renal biopsy following recurrence in case 4, the interstitial fibrosis grade increased to (++). In two patients with GTN, immunohistochemical staining revealed that the infiltrating lymphocytes were predominantly CD4 + T cells, which formed nodular granulomas and were surrounded by CD8 + T cells. A favorable response to steroid therapy was noted in all cases, especially in case 1, 2, and 3. Conclusions The pathological manifestations of RS primarily consist of acute TIN with or without granuloma formation. Quantifying the pathological grade may assist in guiding treatment decisions and predicting prognosis.

Abstract Blasting excavation is widely used in mining, tunneling and construction industries, but it leads to produce ground vibration which can seriously damage the urban communities. The peak particle velocity (PPV) is one of main indicators for determining the extent of ground vibration. Owing to the complexity of blasting process, there is controversy over which parameters will be considered as the inputs for empirical equations and machine learning (ML) algorithms. According to current researches, the burden has controversial impact on the blast-induced ground vibration. To judge whether the burden affects blast-induced ground vibration, the data of ground vibration considering burden have been recorded at the Wujiata coal mine. Correlation coefficient is used to analyze the relationship between variables, the correlation between the distance from blasting center to monitored point (R) and peak particle velocity (PPV) is greatest and the value of correlation coefficient is − 0.67. This study firstly summarizes the most common empirical equations, and a new empirical equation is established by dimension analysis. The new equation shows better performance of predicting PPV than most other empirical equations by regression analysis. Secondly, the machine learning is confirmed the applicability of predicting PPV. Based on the performance assessments, regression error characteristic curve and Uncertainty analysis in the first round of predicting PPV, the random forest (RF) and K-Nearest Neighbors (KNN) show better performance than other four machine learning algorithms. Then, in the second round, based on the artithmetic optimization algorithm (AOA), the optimized random forest (AOA-RF) model as the most accurate model compared with the optimized K-Nearest Neighbors (AOA-KNN) presented in the literature. Finally, the points of predicted PPV which have been informed of danger are marked based on Chinese safety regulations for blasting.

This study aims to develop and implement standard operating procedures (SOPs) for nursing care during DVSS-Si robot-assisted laparoscopic radical prostatectomy (LRP) and to evaluate the clinical outcomes of these procedures. We included 140 patients who underwent robot-assisted LRP: 70 patients who received routine perioperative nursing care (control group) from July 2021 to February 2022, and 70 patients who were provided perioperative care according to the newly established SOPs (intervention group) from March 2022 to December 2022. Comparative analysis of operational metrics revealed that the intervention group had shorter operation position placement times, reduced robot installation times, decreased robot usage durations and fewer adverse events compared to the control group. Additionally, doctor satisfaction levels were significantly higher in the intervention group. In conclusion, the implementation of nursing SOPs for DVSS-Si robot-assisted LRP effectively standardized nursing practices in the operating room, leading to enhanced operational efficiency and improved quality of nursing services.

Abstract The strain-release-driven reactions of bicyclo[1.1.0]butanes (BCBs) have received significant attention from chemists. Notably, 1,2-migratory reactions enabled by BCB-derived B-ate complexes effectively complement the reactions initiated by common BCBs. The desired products are particularly valuable for late-stage transformations due to the presence of the C–B bond. However, asymmetric reactions mediated by BCB-derived boronate complexes have progressed slowly. In this study, we develop an asymmetric synthesis of atropisomers featuring cis-cyclobutane boronic esters facilitated by 1,2-carbon or boron migration of ring-strained B-ate complexes, achieving high enantioselectivity. The reaction is compatible with various aryl, alkenyl, alkyl boronic esters and B2pin2, and shows good compatibility with natural product derivatives. Mechanistic studies are conducted to understand stereoselective control in the dynamic kinetic asymmetric transformations (DYKATs). The target products can undergo a series of transformations, further demonstrating the practicality of this methodology.

Abstract The management of deep brain stimulation (DBS)‐related surgical site infection (SSI) is challenging. This article aimed to report the efficacy of negative pressure wound therapy (NPWT) in treating DBS‐related SSI while preserving all DBS devices. As a retrospective case series in a single center, localized DBS‐related SSI was treated with complete debridement and NPWT, with preserving all DBS devices. Successful infection control was defined as no clinical or microbiological evidence of recurrent infection 3 months after NPWT. Five patients (three females, two males, median age: 64 years) received NPWT for their DBS‐related SSI. The infection was located in the chest, parietal, and retroauricular areas. Only one patient had the extension wires removed due to the heavy contamination, while no DBS devices were removed in the other patients. All patients showed successful infection control without any remarkable side effects 3 months after debridement and NPWT. These findings suggest that NPWT may effectively promote wound healing with a high probability of preserving all DBS devices in DBS‐related SSI.