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Both fine particulate matter (PM2.5) and high-fat diet (HFD) can cause changes in glucose and lipid metabolisms; however, the mechanism of their combined effects on glucose and lipid metabolisms is still unclear. This study aimed to investigate the effects of PM2.5 and HFD co-exposure on glucose and lipid metabolisms and mitochondrial DNA methylation in Wistar rats. PM2.5 and HFD co-treatment led to an increase in fasting blood glucose levels, an alteration in glucose tolerance, and a decrease in high density lipoprotein cholesterol (HDL-C) levels in Wistar rats. In the homeostasis model assessment (HOMA), HOMA-insulin resistance (HOMA-IR) increased and HOMA-insulin sensitivity (HOMA-IS) and HOMA-β cell function (HOMA-β) decreased in rats co-exposed to PM2.5 and HFD. Additionally, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased, and interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA expressions were upregulated in the brown adipose tissue following PM2.5 and HFD co-exposure. Bisulfite pyrosequencing was used to detect the methylation levels of mitochondrially-encoded genes (MT-COX1, MT-COX2 and MT-COX3), and MT-COX3 was hypermethylated in the PM2.5 and HFD co-exposure group. Moreover, MT-COX3-Pos.2 mediated 36.41 % (95 % CI: −27.42, −0.75) of the total effect of PM2.5 and HFD exposure on HOMA-β. Our study suggests that PM2.5 and HFD co-exposure led to changes in glucose and lipid metabolisms in rats, which may be related to oxidative stress and inflammatory responses, followed by mitochondrial stress leading to MT-COX3 hypermethylation. Moreover, MT-COX3-Pos.2 was found for the first time as a mediator in the impact of co-exposure to PM2.5 and HFD on β-cell function. It could serve as a potential biomarker, offering fresh insights into the prevention and treatment of metabolic diseases.

In the field of automatic optical inspection (AOI), this study presents innovative strategies to enhance object detection accuracy while minimizing dependence on large annotated datasets. We initially developed a defect detection model using a dataset of 3579 images across 32 categories, created in collaboration with a major Taiwanese panel manufacturer. This model was evaluated using 12,000 ambiguously labeled images, with improvements achieved through data augmentation and annotation refinement. To address the challenges of limited labeled data, we proposed the Adaptive Fused Semi-Supervised Self-Learning (AFSL) method. This approach, designed for anchor-based object detection models, leverages a small set of labeled data alongside a larger pool of unlabeled data to enable continuous model optimization. Key components of AFSL include the Bounding Box Assigner, Adaptive Training Scheduler, and Data Allocator, which together facilitate dynamic threshold adjustments and balanced training, significantly enhancing the model’s performance on AOI datasets. The AFSL method improved the mean average precision (mAP) from 43.5% to 57.1% on the COCO dataset and by 2.6% on the AOI dataset, demonstrating its effectiveness in achieving high levels of precision and efficiency in AOI with minimal labeled data.

Abstract Background Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. Methods The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. Results Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. Conclusion Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

BackgroundPerfluoroalkyl substances (PFASs) are classified as persistent organic pollutants and have been widely detected in human. Studies investigating the associations between PFASs exposure and estimated glomerular filtration rate (eGFR) yielded inconsistent results, and little is known about the effects of PFASs on eGFR in population without kidney disease. ObjectiveTo explore the associations of exposure to PFASs with eGFR and renal dysfunction in population without kidney disease. MethodsA total of 609 participants with an eGFR > 60 mL·min−1·1.73 m−2 and without renal impairment matched for sex and age (1∶1) were recruited from endocrinology department and medical examination center of two hospitals in Tianjin, China, from April 2021 to March 2022. Each subject was interviewed using a structured questionnaire to collect information about sex, age, height, weight, disease history, smoking, alcohol intake, etc. Clinical parameters were obtained from medical record, such as fasting blood glucose (FBG), creatinine (Cre), total cholesterol (TC), and triglyceride (TG). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by professionals using standard methods. The serum concentrations of PFASs were determined by liquid chromatography/mass spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of PFASs exposure with eGFR and renal dysfunction, respectively. Subgroup analyses stratified by age and sex were also performed to assess the modified effects of covariates on the associations of PFASs exposure with eGFR. ResultsThere were 283 males, accounting for 46.5% of the total population. The mean age of the participants was (56.86±12.47) years, and the average body mass index (BMI) was (25.59±3.84) kg·m−2. Perfluoro-n-octanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoro-n-nonanoic acid (PFNA), perfluoro-n-decanoic acid (PFDA), perfluoro-n-undecanoic acid (PFUnDA), sodium 1H, 1H, 2H, 2H-perfluoro-1-octanesulfonate (6:2 FTS), and perfluoropentane sulfonic acid (PFPeS) were positive in more than 75% of serum samples, and the corresponding median concentrations were 9.50, 1.67, 17.22, 1.86, 1.41, 0.78, 0.42, and 0.43 μg·L−1, respectively. After full adjustments of sex, age, BMI, hypertension, diabetes, TC, TG, smoking, and drinking, the linear regression models showed that log2-transformed PFHxS concentration was negatively associated with eGFR (b=−1.160, 95%CI: −2.280, −0.410). Compared with the lowest exposure tertile, the estimated change of eGFR in the highest tertile for PFHxS was significantly decreased (b=−2.471, 95%CI: −4.574, −0.368). Furthermore, compared with males, the negative association of PFHxS with eGFR was strengthened among females (female: b=−1.281, 95%CI: −2.388, −0.174; male: b=−0.781, 95%CI: −2.823, 1.261, Pinteraction=0.043). ConclusionA significant negative association between serum PFHxS and eGFR is observed in the sampled population without kidney disease, and females are more susceptible to PFASs exposure than the males.

Fine particulate matter (PM2.5) and high-fat diet (HFD) are known to contribute to blood glucose metabolic disorders. However, limited research has investigated the combined impact of PM2.5 and HFD on blood glucose metabolism. This study aimed to explore the joint effects of PM2.5 and HFD on blood glucose metabolism in rats using serum metabolomics and to identify involved metabolites and metabolic pathways. The 32 male Wistar rats were exposed to filtered air (FA) or PM2.5 (real-world inhaled, concentrated PM2.5, 8 times the ambient level, ranging from 131.42 to 773.44 μg/m3) and fed normal diet (ND) or HFD for 8 weeks. The rats were divided into four groups (n = 8/group): ND-FA, ND-PM2.5, HFD-FA and HFD-PM2.5 groups. Blood samples were collected to determine fasting glucose (FBG), plasma insulin and glucose tolerance test and HOMA Insulin Resistance (HOMA-IR) index was calculated. Finally, the serum metabolism of rats was analyzed by ultra-high performance liquid chromatography/mass spectrometry (UHPLC-MS). Then we constructed the partial least squares discriminant analysis (PLS-DA) model to screen the differential metabolites, and performed pathway analysis to screen the main metabolic pathways. Results showed that combined effect of PM2.5 and HFD caused changes in glucose tolerance, increased FBG levels and HOMA-IR in rats and there were interactions between PM2.5 and HFD in FBG and insulin. By metabonomic analysis, the serum differential metabolites pregnenolone and progesterone, which involved in steroid hormone biosynthesis, were two different metabolites in the ND groups. In the HFD groups, the serum differential metabolites were L-tyrosine and phosphorylcholine, which involved in glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. When PM2.5 and HFD coexist, they may lead to more severe and complex effects on glucose metabolism by affecting lipid metabolism and amino acid metabolism. Therefore, reducing PM2.5 exposure and controlling dietary structure are important measures for preventing and reducing glucose metabolism disorders.

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed (P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence (P = 0.724) or glans dehiscence (P = 0.246) except for postoperative meatus stenosis (P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different (P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use (P = 0.020), diabetes (P = 0.003), current/former smoking (P = 0.019), coronary heart disease (P < 0.001), and stricture length (P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.

Summary: Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6–55.4) and the DCR was 77.8% (90% CI, 56.1–92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0–not reach), and the median PFS was 7.2 months (90% CI, 4.4–13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3–4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Neuronal apoptosis is a major pathological process associated with neurological dysfunction in neonates after hypoxic–ischemic brain damage (HIBD). Our previous study demonstrated that oxymatrine (OMT) exerts potential neuroprotective effects on neonatal rats subjected to hypoxic–ischemic insult. However, the underlying molecular mechanism remains unclear. In this study, we investigated the effects of OMT-mediated neuroprotection on neonatal HIBD by attempting to determine its effect on the Wnt/β-catenin signaling pathway and explored the underlying mechanism. Both 7-day-old rat pups and primary hippocampus neurons were used to establish the HIBD and oxygen-glucose deprivation (OGD) injury models, respectively. Our results demonstrated that OMT treatment significantly increased cerebral blood flow and reduced S100B concentration, infarct volume, and neuronal apoptosis in neonatal rats. In vitro, OMT markedly increased cell viability and MMP level and decreased DNA damage. Moreover, OMT improved the mRNA and protein levels of Wnt1 and β-catenin, inhibited the expression of DKK1 and GSK-3β, enhanced the nuclear transfer of β-catenin, and promoted the binding activity of β-catenin with Tcf-4; however, it downregulated the expression of cleaved caspase-3 and cleaved caspase-9. Notably, the introduction of XAV-939 (a Wnt/β-catenin signaling inhibitor) reversed the positive effects of OMT both in vivo and in vitro. Collectively, our findings demonstrated that OMT exerted a neuroprotective effect on neonatal HIBD by inhibiting neuronal apoptosis, which was partly via the activation of the Wnt/β-catenin signaling pathway.

Abstract Background Juvenile xanthogranuloma (JXG) is a kind of non-Langerhans cell histiocytosis, usually with skin lesions as the main manifestation. It rarely occurs in other tissues or organs and even more rarely is it found in the skull. Here, we report a case of xanthogranuloma derived from the temporal bone that was not present in any other parts of the body. Case presentation A 15-year-old boy had an unaccountable right migraine for 7 months. A mass with tenderness was located behind his right ear. The mass gradually increased in size, and his headache continued. Eventually, he came to our hospital for treatment. A computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a cystic solid mass in the right temporo-occipital region with skull destruction. The clinical diagnosis was haemangiopericytoma and skull-derived tumour. Haematological and biochemical results were as follows: alanine aminotransferase (ALT) 7 U/L; aspartate aminotransferase (AST) 12 U/L; basophil percentage (BASO%) 1.2%; normal coagulation. The patient was successfully treated with total surgical resection of the tumour. Postoperative histopathology examination showed xanthogranuloma, and his prognosis after surgery was good. Conclusions Because JXG rarely occurs in the skull and lacks typical imaging findings, an accurate diagnosis is difficult. The diagnosis of this disease mainly depends on pathological examination and immunohistochemistry. If feasible, many intracranial lesions can be cured through complete resection.

Abstract Correlated metals with high carrier density and strongly correlated electron effects provide an alternative route to achieve transparent conducting materials, different from the conventional degenerately doped wide‐bandgap transparent conducting oxides (TCO). The extremely low electrical resistivity and high optical transparency in the ultraviolet‐visible spectral range shown in 4d correlated metals present an advantage over conventional TCOs. However, most of the 4d correlated metals are grown epitaxially on single crystal substrates. Here, it has been shown that Ca2Nb3O10 nanosheets with different buffer layers promote the growth of high‐quality 4d2 SrMoO3 films on fused silica substrates, overcoming the use of expensive and size‐limited single‐crystal substrates. The room temperature electrical resistivity of SrMoO3 is as low as 61 µΩ cm, the lowest reported value on amorphous transparent substrates to date, without compromising its high optical transmittance. 4d1 correlated metal SrNbO3 on Ca2Nb3O10 nanosheets also exhibits similarly high optical transmittance but a higher room temperature resistivity of 174 µΩ cm. These findings facilitate the use of highly conducting and transparent 4d correlated metals not only as TCOs on technologically relevant substrates for the applications in the ultraviolet‐visible spectral range but also as electrodes for other oxide‐based thin film technologies.

Trastuzumab is a standard molecular targeted therapy for human epidermal growth factor receptor 2(HER2) -positive breast cancer, which can significantly improve the survival of patients with this molecular subtype of breast cancer. However, the clinical problem of onset or secondary resistance to trastuzumab has limited its efficacy. Therefore, it is very important to explore the mechanism of trastuzumab resistance and formulate countermeasures. Our study described the underlying molecular mechanism of trastuzumab resistance including ERBB2 mutations and nuclear localization, transcriptional and post-translational alterations of ERBB2, over-activation of bypass signaling pathways activation and so on. Then summarize the potential emerging predicting biomarkers and therapeutic strategies for trastuzumab resistance, in order to provide research direction for reversing trastuzumab resistance.

Abstract Background α‐1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients. Methods Serum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed. Results Relative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p 12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p

A nano‐immunomodulator (R‐NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π‐extended NIR‐absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R‐NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll‐like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R‐NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R‐NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH‐liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R‐NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively. [ABSTRACT FROM AUTHOR]

CoN nanoparticles and carbon nanotubes hybrid supported on carbon foam (INPs-CoN/CNTs-CF) electrocatalyst was synthesized by one-step pyrolysis of irregular nanoparticles ZIF-67 (ZIF-67-INPs) with melamine foam. The INPs-CoN/CNTs-CF electrocatalyst exhibited remarkable activity for ORR with a high half-wave potential of 0.862 V vs. RHE, and a good HER electrocatalytic activity with overpotential of 180 mV at 10 mA cm−2 and a Tafel slope of 102.5 mV dec−1. This electrocatalyst can be a promising bifunctional alternative for both ORR and HER. This work provides a new insight for the design of new-type multi-functional electrocatalysts for practical applications.