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Sui-Yi Xu,1,* Hui-Juan Li,2,* Shun Li,2 Qian-Qian Ren,1 Jian-Lin Liang,1 Chang-Xin Li1 1Department of Neurology, Headache Center, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Xin Li, Department of Neurology, The First Hospital of Shanxi Medical University, Jiefangnan 85 Road, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 15103513579, Email lichangxin0351@sina.comAbstract: High temperature requirement serine peptidase A1 (HTRA1) related cerebral small vessel disease (CSVD) includes both symptomatic heterozygous HTRA1 variant carrier and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) patients. Presently, most reported symptomatic heterozygous HTRA1 variant carrier cases are sporadic family reports with a lack of specific characteristics. Additionally, the molecular mechanism of heterozygous HTRA1 gene variants is unclear. We conducted this review to collect symptomatic carriers of heterozygous HTRA1 gene variants reported as of 2022, analyzed all pathogenicity according to American College of Medical Genetics and Genomics (ACMG) variant classification, and summarized the cases with pathogenic and likely pathogenic HTRA1 variants gender characteristics, age of onset, geographical distribution, initial symptoms, clinical manifestations, imaging signs, HTRA1 gene variant information and to speculate its underlying pathogenic mechanisms. In this review, we summarized the following characteristics of pathogenic and likely pathogenic symptomatic HTRA1 variant carriers: to date, the majority of reported symptomatic HTRA1 carriers are in European and Asian countries, particularly in China which was found to have the highest number of reported cases. The age of first onset is mostly concentrated in the fourth and fifth decades. The heterozygous HTRA1 gene variants were mostly missense variants. The two variant sites, 166– 182 aa and 274– 302 aa, were the most concentrated. Clinicians need to pay attention to de novo data and functional data, which may affect the pathogenicity analysis. The decrease in HtrA1 protease activity is currently the most important explanation for the genetic pathogenesis.Keywords: stroke, HTRA1 gene, ACMG criteria, heterozygous variant, symptomatic carrier

This study was designed to evaluate the diagnostic efficacy of relevant parameters of 18 F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by 18 F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant ( p  < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z =  -1.131, p  = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p  = .010] and 0.758 (95% CI: 0.613-0.938, p  = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p  < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z =  -2.043, p  = .041). In a nutshell, 18 F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

Based on our previous study [Wang et al., J. Chem. Phys. 153, 184102 (2020)], we generalize the theory of molecular emission power spectra (EPS) from one molecule to multichromophoric systems in the framework of macroscopic quantum electrodynamics. This generalized theory is applicable to ensembles of molecules, providing a comprehensive description of the molecular spontaneous emission spectrum in arbitrary inhomogeneous, dispersive, and absorbing media. In the far-field region, the analytical formula of EPS can be expressed as the product of a lineshape function (LF) and an electromagnetic environment factor (EEF). To demonstrate the polaritonic effect on multichromophoric systems, we simulate the LF and EEF for one to three molecules weakly coupled to surface plasmon polaritons above a silver surface. Our analytical expressions show that the peak broadening originates from not only the spontaneous emission rates but also the imaginary part of resonant dipole-dipole interactions (non-Hermitian interactions), which is associated with the superradiance of molecular aggregates, indicating that the superradiance rate can be controlled through an intermolecular distance and the design of dielectric environments. This study presents an alternative approach to directly analyze the hybrid-state dynamics of multichromophoric systems coupled with polaritons., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Context: Since the outbreak of COVID-19 in late 2019, the transmission dynamics and clinical presentation patterns of influenza A (Flu A) virus have undergone changes., Objectives: This article conducted a comparative analysis in clinical characteristics and laboratory results of pediatric patients with Flu A before, during, and after the COVID-19 pandemic., Methods: The medical records of 885 children hospitalized with Flu A virus infection at a tertiary hospital in Guangdong Province, China, were retrospectively analyzed. Flu A was confirmed in these cases using a direct immunofluorescence antigen assay. The clinical data for this study span from January 1, 2018, to May 31, 2023., Results: In our study, we observed a total of 340 cases before the COVID-19 pandemic, 196 cases during the pandemic, and 349 cases after the pandemic. Patients after the pandemic had a higher median age on admission (5.66 years, range 3.41-7.70) and exhibited more respiratory symptoms such as cough, sore throat, and nasal stuffiness. The length of hospital stay was longer, and there was a higher percentage of patients with fever duration ≥ 5 days among Flu A patients during the pandemic. Compared to before and during the COVID-19 pandemic, Flu A patients after the pandemic showed significantly reduced white blood cell (WBC) and platelet (PLT) counts (P < 0.001), along with elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in laboratory indexes (P < 0.001). Furthermore, more hospitalized children after the pandemic were diagnosed with benign acute childhood myositis (BACM)., Conclusion: Our research results indicates a significant decrease in Flu A cases during the COVID-19 pandemic, and hospitalized children with Flu A have more severe clinical symptoms after the COVID-19 pandemic. These findings have implications for public health policy and clinical management of Flu A cases., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving humans were approved by the Institute Ethics Committee of Chaozhou Central Hospital (No. 2023009) and People’s Hospital of Yangjiang (No. 20230003). The studies were conducted in accordance with the local legislation and institutional requirements. The Ethics Committee/Institutional Review Board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: A phyllodes tumor (PT) is a biphasic fibroepithelial lesion that is most commonly found in breast tissue, whereas it is uncommon in ureter tissue. Only one case has been documented so far. There are some similarities in histology and clinical characteristics between this type of tumor and PT of the female breast: the lesions can be surgically removed, but some recur locally and invade directly into the breast. This case of a primary PT of the ureter is useful for pathologists and clinicians., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was obtained from the Institutional Research Ethics Board of Huzhou central Hospital. Consent was obtained from the patient in writing. Consent for publication: All the authors agree with this case for publication. Written informed consent was obtained from the patient for publication of this case report. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The use of lithium-rich manganese-based oxides (LRMOs) as the cathode in all-solid-state batteries (ASSBs) holds great potential for realizing high energy density over 600 Wh kg -1 . However, their implementation is significantly hindered by the sluggish kinetics and inferior reversibility of anionic redox reactions of oxygen in ASSBs. In this contribution, boron ions (B 3+ ) doping and 3D Li 2 B 4 O 7 (LBO) ionic networks construction are synchronously introduced into LRMO materials (LBO-LRMO) by mechanochemical and subsequent thermally driven diffusion method. Owing to the high binding energy of B─O and high-efficiency ionic networks of nanoscale LBO complex in cathode materials, the as-prepared LBO-LRMO displays highly reversible and activated anionic redox reactions in ASSBs. The designed LBO-LRMO interwoven structure enables robust phase and LBO-LRMO|solid electrolyte interface stability during cycling (over 80% capacity retention after 2000 cycles at 1.0 C with a voltage range of 2.2-4.7 V vs Li/Li + ). This contribution affords a fundamental understanding of the anionic redox reactions for LRMO in ASSBs and offers an effective strategy to realize highly activated and reversible oxygen redox reactions in LRMO-based ASSBs., (© 2024 Wiley‐VCH GmbH.)

Purpose: Inclusive education plays a crucial role in integrating students with special educational needs (SEN) into mainstream schools, where the attitudes of pre-service teachers are pivotal. Despite recognizing the significance of these attitudes, there is currently a gap in understanding the perspectives of students attending normal universities in China regarding inclusive education practices. This study aims to bridge this gap by creating the Chinese version of the Normal Universities Students' Attitudes Toward Inclusive Education Scale (NUSATIES) and examining its psychometric properties., Methods: In the context of China, this study validated and assessed the reliability of the Chinese adaptation of the NUSATIES among a sample of 4,091 students from normal universities. Confirmatory factor analysis (CFA) was employed to confirm the scale's structural integrity, discriminant validity, and convergent validity. Additionally, Cronbach's alpha and composite reliability (CR) were used to evaluate the scale's internal consistency and reliability., Results: The findings indicated that the Chinese version of the NUSATIES possessed robust validity and reliability, which comprises three factors (i.e., cognitive, affective, and behavioral intention). The findings revealed that normal university students' attitudes significantly varied based on specialty; students specializing in special education exhibited more positive attitudes towards inclusive education than those in general education., Conclusion: These findings indicate that the scale is effective in measuring attitudes toward inclusive education in Chinese-speaking countries. This study significantly contributes to the field by emphasizing the importance of positive attitudes among normal university students in fostering inclusive education and by offering a validated tool for assessing these attitudes., Competing Interests: Declarations. Human Ethics and Consent to participate declarations missing: Approval was obtained from the ethics committee of WuYi University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. The study was conducted with the informed consent of the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ca 2+ overload is one of the most widely causes of inducing apoptosis, pyroptosis, immunogenic cell death, autophagy, paraptosis, necroptosis, and calcification of tumor cells, and has become the most valuable therapeutic strategy in the field of cancer treatment. Nevertheless, several challenges remain in translating Ca 2+ overload-mediated therapeutic strategies into clinical applications, such as the precise control of Ca 2+ dynamics, specificity of Ca 2+ homeostasis dysregulation, as well as comprehensive mechanisms of Ca 2+ regulation. Given this, we comprehensively reviewed the Ca 2+ -driven intracellular signaling pathways and the application of Ca 2+ -based biomaterials (such as CaCO 3 -, CaP-, CaO 2 -, CaSi-, CaF 2 -, and CaH 2 -) in mediating cancer diagnosis, treatment, and immunotherapy. Meanwhile, the latest researches on Ca 2+ overload-mediated therapeutic strategies, as well as those combined with multiple-model therapies in mediating cancer immunotherapy are further highlighted. More importantly, the critical challenges and the future prospects of the Ca 2+ overload-mediated therapeutic strategies are also discussed. By consolidating recent findings and identifying future research directions, this review aimed to advance the field of oncology therapy and contribute to the development of more effective and targeted treatment modalities., 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 Ltd. All rights reserved.)

The popularity of social networking sites increases opportunities for upward social comparison, potentially affecting individuals' subjective well-being. However, research on how this comparison impacts well-being's sub-components (i.e., positive affect, negative affect, and life satisfaction) is scarce. This study, based on social comparison theory and the full theoretical construct of subjective well-being, explores these relationships and their mechanisms. A total of 970 Chinese youth participants (M age  = 19.42 years, SD = 2.01) completed self-report measures. The results showed that the independent mediating effect of envy and the chain mediating effect of self-concept clarity and envy contributed to all three models. In addition, the independent mediating effect of self-concept clarity only contributed to the model for negative affect. This study emphasizes that the construct of envy mediates the effect of upward social comparison on the sub-components of subjective well-being and further demonstrates a strong impact of upward social comparison on negative affect., (© 2024 British Psychological Society.)

Background: Neuropathic pain (NP) constitutes a significant burden for individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous research has suggested that the analgesic effects of NP are mediated by dopamine (DA) neurons in the ventral tegmental region (VTA) through projections to various brain regions. A decrease in VTA dopamine neurons following NP may contribute to prolonged pain. It has been revealed that inflammatory activation triggers necroptosis by stimulating mixed lineage kinase domain-like protein (MLKL), leading to progressive neuronal demise. Recent research from many studies has revealed that IL-17-induced necroptosis plays an important role in neuroinflammation and neuronal damage. To our knowledge, few studies have hitherto investigated how IL-17-induced necroptosis may contribute to neuropathic pain. Hydrogen sulfide (H 2 S) treatment is commonly used for neuropathic pain, although the exact mechanisms remain unclear. Sodium hydrosulfide (NaHS), a common H 2 S delivery method in medicine, has also been shown to exert neuroprotective effects against neuropathic pain. This study aimed to investigate the link between IL-17-induced necroptosis of dopamine neurons in the VTA and neuropathic pain. Additionally, we explored whether H 2 S treatment could reduce the loss of VTA dopamine neurons, thereby lowering neuropathic pain in a chronic constriction injury (CCI) model., Methods: This study employed a CCI animal model created using a sciatic nerve ligation approach. To investigate the effect of H 2 S treatment on neuropathic pain, NaHS was injected intrathecally into CCI model mice. The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated to assess the mice's pain thresholds. Additional experiments, including electrophysiological studies and immunofluorescence assays, western blotting, real-time quantitative Polymerase Chain Reaction (PCR) were conducted to elucidate the precise mechanism underlying the analgesic effects of H 2 S therapy on neuropathic pain., Results: In mice exposed to CCI, there was a significant decrease in dopamine neurons, a reduction in MWT and TWL, decreased expression of tyrosine hydroxylase (TH) protein and TH mRNA and an increase in VTA firing rate and MLKL colocalization with DA neurons (all p < 0.05). However, treatment with NaHS remarkably restored these changes. Additionally, IL-17 administration negated the neuroprotective benefit of H 2 S after CCI., Conclusion: H 2 S therapy reduces CCI-induced neuropathic pain in mice. This protective mechanism may be linked to the prevention of IL-17-induced necroptosis of dopamine neurons in the VTA., Competing Interests: Declaration of Competing Interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial competing interest in the subject matter or materials discussed in this manuscript by any of the authors., (Copyright © 2024. Published by Elsevier Inc.)

Reported herein is a convenient and efficient method for one-pot, catalytic reductive amination, as well as the first multi-component tandem reductive amination-functionalization of bench-stable and readily available common carboxylic esters. This method is based on the cationic [Ir(COD) 2 ]BArF-catalyzed chemoselective hydrosilylation of esters, followed by one-pot acid-mediated amination and nucleophilic addition. The reaction was conducted under mild conditions at a very low catalyst loading (0.1 mol % of Ir), which could be further reduced to 0.001 mol %, as demonstrated by a reaction at a 15 g scale. The method is highly versatile, allowing the use of esters with or without α-protons for the N-mono-alkylation of primary and secondary amines to produce diverse secondary and tertiary amines, as well as α-branched/functionalized amines. The method is highly chemoselective and tolerates a variety of functional groups such as bromo, trifluoromethyl, ester, and cyano groups. The value of the method was demonstrated by the one-step catalytic synthesis of two bio-relevant N-mono-methyl α-amino esters and the antiparkinsonian agent piribedil, as well as by the use of two shorter chain triglycerides as alkylating feedstock., (© 2024 Wiley-VCH GmbH.)

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT., Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals. Serum GFAP and UCH-L1 levels were measured 24 hours after IVT. Cases from 1 hospital were randomly assigned to the training (70%) and testing (30%) cohorts for internal validation. The external validation cohort included patients from the other 15 hospitals. Cutoff levels of GFAP and UCH-L1 for assessing the absence of HT were established in the training cohort and subjected to internal and external verification., Results: A total of 1063 patients were included. Both GFAP and UCH-L1 levels were independently associated with HT, infarct volume, and 3-month outcome; levels lower than cutoff (12.6 and 63.1 pg/mL, respectively) excluded patients with HT with a negative predictive value of 98.31% (95% CI, 89.70%-99.91%) and detection sensitivity of 98.08% (95% CI, 88.42%-99.90%) in the training cohort. In the testing and validation cohorts, negative predictive value was 100% (95% CI, 75.93%-100%) and 100% (95% CI, 82.19%-100%), respectively, and the sensitivity was 100% (95% CI, 80.76%-100%) and 100% (95% CI, 77.08%-100%), respectively., Conclusions: Serum GFAP and UCH-L1 levels exhibit high sensitivity and negative predictive value for indicating the absence of HT 24 hours after IVT, which supports their potential role in assessing patients' condition after IVT.

Simulating the changes in ecosystem service value induced by land use changes in the peak cluster depression basin of southwestern Guangxi under multiple scenarios is of great importance for ensuring ecological security in the basin and enhancing regional ecosystem service value capabilities. Based on the CA-Logistic-Markov model, the land use of the study area was simulated under natural development, food security, and ecological protection scenarios in 2030. The ecosystem service value was calculated under each scenario using the equivalent factor correction model, and the spatiotemporal dynamic characteristics of the ecosystem service value in the peak cluster depression basin of southwestern Guangxi were quantitatively analyzed. The results showed as follows： ① Compared with the current situation of land use in 2020 and the predicted simulated land use in 2020, the standard Kappa index was 0.917, the location Kappa index was 0.952, and the numerical Kappa index was 0.958. In the simulation of the land use pattern of the peak cluster basin in southwest Guangxi in 2030, the CA-Markov model had high accuracy and reference-ability. ② Ecosystem service values in the study area for the periods 2000-2020 were 270.881 billion, 275.78 billion, and 278.332 billion yuan, indicating an overall upward trend. ③ The value of ecosystem services in the natural development, the food security, and the ecological protection scenarios was 282 138 million, 273 206 million, and 284 143 million, respectively. The study area exhibited a spatial distribution of ecosystem service values with higher values in the northwest and lower values in the southeast. In comparison to that in 2020, the ecosystem service value significantly decreased under the food security scenario, reflecting ecosystem degradation. Meanwhile, ecosystem service values increased under the natural development and ecological protection scenarios, signifying an improvement in ecological environmental quality. ④ Ecosystem service value hot spots and cold spots with high confidence had strong clustering and the hot spots were mainly concentrated in the northwestern mountainous area, whereas the cold spots with high confidence were mainly distributed in the southeastern plain area of the study area. The research results revealed the spatiotemporal pattern of land use change and ecosystem service value in the peak cluster depression basin of southwestern Guangxi under multiple scenarios, which can provide scientific basis for optimizing land use structure and spatial pattern and enhancing ecosystem services.

Utilizing the online monitoring data of volatile organic compounds （VOCs） and ozone （O 3 ） in the Shijiazhuang high-tech industrial development zone during October 2020, the pollution characteristics of VOCs were analyzed. Subsequently, ·OH estimation, secondary organic aerosol formation potential （SOAP）, and ozone formation potential （OFP） were applied to assess the chemical reactivity of VOCs. Additionally, the source apportionment was identified using the positive matrix factorization （PMF） model. The results revealed that the hourly φ [total VOCs （TVOCs）] were （11-281）×10 -9 , and the components were ranked by volume fraction in the following order： oxygenated volatile organic compounds （OVOCs） （60.83%）, alkanes （19.98%）, halohydrocarbons （5.64%）, aromatics （5.91%）, alkenes （4.83%）, and alkynes （2.48%）. Although the VOC concentration levels posed negligible non-carcinogenic risks to human health, benzene and ethylbenzene presented carcinogenic risks. The m / p -xylene to ethylbenzene ratio （X/E） varied from 2.5 to 3.4, indicating short-range transport of fresh air masses. Based on the X/E value, the ·OH concentration was 1.75×10 6 molecule·cm -3 , and the ·OH exposure from 07：00 to 14：00 was calculated as 3.77×10 10 molecule·s·cm -3 . Aromatics played a dominant role in SOA, with a contribution rate as high as 93.35%, while alkenes dominated O 3 formation, with the OFP contribution rate reaching up to 46.79%. By applying the PMF model, five major VOC sources were identified, including industrial sources （37.20%）, process flow and solvent use （33.80%）, vehicle and oil/gas evaporation sources （15.47%）, combustion sources （8.03%）, and plant emissions （5.50%）. Industrial and process emissions emerged as the primary contributors to VOCs in the ambient air of the high-tech zone, necessitating targeted control measures within this region.

Purpose: To develop and validate a prognostic and predictive model integrating deep learning MRI features and clinical information in patients with stage II nasopharyngeal carcinoma (NPC) to identify patients with a low risk of progression for whom intensity-modulated radiotherapy (IMRT) alone is sufficient., Methods: This multicenter, retrospective study enrolled 999 patients with stage II NPC from two centers. 3DResNet was used to extract deep learning MRI features and eXtreme Gradient Boosting model was employed to integrate the pre-trained features and clinical information to obtain an overall score for each patient. Based on the optimal cutoff value of the overall score, patients were stratified into high- and low- risk groups. Model performance was evaluated using concordance indexes (C-indexes), the area under the curve (AUC) values and calibration tests. Survival curves were used to analyze the clinical benefits of additional chemotherapy in each risk group., Results: The combined model achieved a concordance index of 0.789 (95 % confidence interval [CI] 0.787-0.791), 0.768 (95 % CI 0.764-0.771), and 0.804 (95 % CI 0.801-0.807) for the training, internal validation, and external test cohorts, respectively, demonstrating a statistically significant improvement compared to the MRI model, T Stage, and N Stage. An overall score of < 0.405 in patients was significantly associated with a low risk of progression. In the low-risk group, patients treated with IMRT alone had comparable or even superior progression-free survival (PFS) compared to those who received additional chemotherapy., Conclusion: The model demonstrated a satisfactory prognostic and predictive performance for PFS. Patients with stage II NPC were stratified into different risk groups to help identify optimal candidates who could benefit from IMRT alone., 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.)

Introduction The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is under-utilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore. Methods We will perform a prospective, multi-center, Type II hybrid effectiveness-implementation study with a post design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train "genetic nephrologists" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes; steroid-resistant primary nephrotic syndrome; apparent familial IgA nephropathy; or chronic kidney disease with no apparent cause) and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease) and cost-effectiveness. Conclusion This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care., (The Author(s). Published by S. Karger AG, Basel.)

Objectives: To explore the genotypic and phenotypic characteristics of HBB : c.316-146T > G carriers in China., Methods: The blood routine parameters and hemoglobin electrophoresis data of carriers were analyzed using PCR combined with reverse dot blot (RDB), gap-PCR, and DNA sequencing., Results: The blood routine parameters of all these three cases were MCV < 82fl and MCH < 27pg, and hemoglobin electrophoresis showed HbA 2  ≥ 4.60%. Genetic testing results: two cases were heterozygous mutations of HBB :c.316-146T > G, the other one was heterozygous mutation of HBB :c.316-146T > G combined with - SEA deletion., Conclusion: The hematological phenotype of HBB :c.316-146T > G mutation carriers is similar to that of common β + heterozygous mutations, presenting with hypochromic, microcytic red cell indices. If the hematological phenotype does not match the results of genetic testing, further detection techniques such as Sanger sequencing, MLPA, next-generation sequencing (NGS), etc. are required to avoid missing rare or novel mutation types.

In our previous research, we reported that administering probiotics Lactobacillus reuteri and Clostridium butyricum (LCs) before cisplatin treatment effectively modifies structures of the gut microbiota and restore ecological balance and significantly increases butyrate levels, a process closely associated with reducing cisplatin-induced nephrotoxicity. This study aims to investigate further whether the elevation of metabolite butyrate in the gut, promoted by probiotics LCs, can effectively mitigate the nephrotoxic effects of cisplatin and the progression of renal senescence in rats. Results show that butyrate administration significantly improved kidney function and decreased renal fibrosis in a dose-dependent manner compared to the cisplatin group. Its effects were associated with reductions in inflammatory responses, evidenced by decreased levels of key inflammatory markers, including KIM-1, MPO, NOX2, F4/80, and TGF-β1, alongside increased production of the anti-inflammatory cytokine IL-10. Furthermore, the butyrate intervention ameliorated cisplatin-induced gut microbiota dysbiosis, preserving the structure and diversity of healthy microbial communities. Specifically, we observed a decrease in the abundance of Escherichia&#95;Shigella and Blautia, alongside an increase in the abundance of the butyrate-producing genus Roseburia. Notably, Escherichia&#95;Shigella exhibited a positive correlation with the pro-inflammatory factor MPO, while displaying a negative correlation with the anti-inflammatory cytokine IL-10. Butyrate also attenuated the cisplatin-induced expression of senescence markers p21 and p16 in kidney tissue. It alleviated the cisplatin-increased senescence-associated beta-galactosidase activity and reactive oxygen species production in SV40 MES-13 cells. These results indicate that butyrate, derived from the gut microbiota, may exert a protective effect against cisplatin-induced kidney damage by regulating microbiota balance and anti-inflammatory effects., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To summarize and analyze the clinical characteristics of the Hb Phnom Penh ( HBA1 :c.354&#95;355insATC) variant in the Chinese population, and to guide clinical diagnosis and genetic counseling for hemoglobin disorders., Methods: Peripheral blood samples were collected from patients, and hematological parameters, hemoglobin electrophoresis, and glycated hemoglobin chromatography were analyzed. PCR combined with reverse dot blot hybridization (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), Sanger sequencing, and third-generation sequencing (TGS) were performed to determine the gene variant., Results: A total of 20 cases were examined, which included 11 neonates, 5 infants aged from 1 month to 6 months, and 4 adults. Hb Bart's band was measured in 14 infants. Thirteen infants (9 neonates and 4 infants of 1 month old) showed low levels of Hb Bart's bands (<1%), while one newborn exhibited a significantly elevated level of the Hb Bart's band (13.8%). Two adult patients were tested for glycated hemoglobin and had high levels at 7.0% and 7.2%, respectively, despite having normal blood glucose levels and no history of diabetes, indicating the presence of abnormal hemoglobin. Genetic testing confirmed that all 20 cases carried the HBA1 :c.354&#95;355insATC mutation, with one case being a compound mutation of - SEA /αα Phnom Penh ., Conclusion: The HBA1 :c.354&#95;355insATC mutation leads to the production of abnormal hemoglobin (Hb Phnom Penh). Infants may exhibit low levels of Hb Bart's bands on hemoglobin electrophoresis, which have no salient pathological significance. The detection of abnormal HbA1c values suggests that this abnormal haemoglobin may be present.

Objective: To analyze the hematological phenotype and genotype of HbA2 : c.96-2A > G carriers., Methods: The blood routine parameters and hemoglobin electrophoresis of rare cases were analyzed and identified by PCR combined with reverse dot blot (RBD-PCR), GAP-PCR and DNA sequencing., Results: Among the 7 patients, one adult patient had normal hemoglobin levels, with slightly decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Hb Bart's band was found in 6 neonates by hemoglobin electrophoresis, of which the content of Hb Bart's band in 1 neonate was 15.80%, and the content of Hb Bart's band in the other 5 neonates was 0.30%-0.90%. The results of genetic analysis showed that all the 7 patients had HbA2 : c.96-2A > G (IVS-I-116A > G) mutation, in which 1 case was compounded with - SEA deletion., Conclusion: HbA2 : c.96-2A > G mutation carriers exhibit the phenotype of α-thalassemia, and when the HbA2 :c.96-2A > G mutation is combined with - SEA deletion, an intermediate phenotype of anemia is produced.

Uveal melanoma (UM) is the most common malignant intraocular tumor with the trait of distant metastases. Currently, the standard clinical therapy results in suboptimal outcomes due to ineffective inhibition of tumor metastasis. Thus, developing novel therapeutic modalities for UM remains a critical priority. Herein, we have developed an injectable nanocomposite hydrogel (HA-DOX/LAP gel) through integrating hyaluronic acid-based drug-loaded nanoparticles into an alginate-dopamine gel, delivering the chemotherapeutic drugs, lapatinib and doxorubicin for combinational treatment of UM. HA-DOX/LAP gel is fabricated in situ by a simple injection of the mixed precursor solution into tumor sites and maintains in vivo for more than 21 days. The entrapped drug-loaded nanoparticles can gradually release from HA-DOX/LAP gel, enhancing tumor targeting and penetration, and synchronously releasing lapatinib and doxorubicin into the acidic intracellular environment to synergistically destroy UM cells. In vivo anti-tumor studies conducted in MuM-2B tumor models demonstrated that HA-DOX/LAP gel significantly impedes tumor growth, diminishes postoperative recurrence, and prolongs overall survivals of UM tumor-bearing mice through only single injection. Remarkably, the escaped drug-loaded nanoparticles effectively reduce the risk of tumor metastases. Our findings provide new insights for the development of multifunctional nanocomposite-incorporating combination therapy against UM by targeting tumor recurrence and metastases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bacterial septicemia caused by Aeromonas hydrophila is one of the common bacterial diseases in aquaculture. Antimicrobial peptides, including hepcidin, are key components of the innate immune system in fish, playing a role in defense against pathogens. This study investigated the defense patterns of hepcidin in mandarin fish (Siniperca chuatsi) following A. hydrophila infection using gene expression analysis and in vitro antibacterial assays. We measured changes in the expression of iron metabolism-related genes (hepcidin, fpn, ftn, tf, tfr1) and immune-related genes (il-1β, il-6, il-8, il-10, tnf-α, socs3, nkap, tlr1, tlr2) in the intestine post-infection. MBC experiment demonstrated that the hepcidin synthetic peptide has an inhibitory effect on the growth of V. parahaemolyticus (32 μg/ml), A. hydrophilus (64 μg/ml), and F. columnaris (128 μg/ml), but not E. tarda (>256 μg/ml). After A. hydrophilus challenge, fpn, tf and tfr1 with peak expression at 24 hpi (2.75), 12 hpi (4.43) and 6 hpi (7.41), respectively. Hepcidin and ftn expression was highest at 48 hpi (115.01) and 72 hpi (4.16). The Fe 2+ content peaked at 6 hpi (2.64 μmol/l) and reached its lowest at 12 hpi (1.12 μmol/l) in the intestine. After pathogen challenge, il-1β, il-8, socs3, tlr2, and hepcidin showed trends of increased and then decreased, with peak expression at 72 hpi (5.13, 37.05, 3.08) and 48 hpi (5.35, 115.01), respectively. These findings suggested that hepcidin plays a key role in the defense against A. hydrophila: initially restricting bacterial growth through iron metabolism (0-48 hpi), and later modulating immune responses via the TNF (by inducing il-1β and socs3) and Toll-like receptor pathways (by inducing il-8 and tlr2) (48-96 hpi). This study provides novel insights into the immune function of hepcidin in fish and its potential application in managing bacterial infections in aquaculture., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Uveal melanoma (UM) is the most common intraocular primary malignancy in adults with highly metastatic characteristics. Currently, there are no effective therapies to prevent metastasis formation in UM, resulting in a poor prognosis. Herein, we report a novel lapatinib-loaded reductive-responsive nanoparticle platform prepared via the self-assembly of amphiphilic hyaluronic acid-cystamine-cholesteryl hemisuccinate conjugate to suppress the distant metastasis of UM. The platform can maintain a stable nanosphere structure in the physiological environment and effectively deliver the drug to UM tumor sites, enhancing intratumoral drug accumulation and penetration. Upon endocytosis, lapatinib-loaded nanoparticles rapidly disintegrate triggered by intracellular glutathione and release the payload, leading to considerable suppression of MuM-2B cell proliferation, invasion, and migration. Systemic administration of lapatinib-loaded nanoparticles into mice bearing lung metastases of UM resulted in significantly higher metastasis suppression compared to free lapatinib, with histological analyses indicating no detectable toxicity. This nanotherapeutic platform is expected to provide a promising approach for the safe and efficient prevention of metastasis in UM., 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.)

Natural carotenoids from microalgae have received more attention as an alternative source. In this study, fulvic acid (FA), a plant growth regulator, was used to enhance carotenoid accumulation in microalgae Dunaliella bardawil rich in lutein. However, the addition of FA promoted pigment synthesis but also exhibited an inhibitory effect on biomass. Therefore, the optimization of culture conditions was performed to further enhance carotenoid accumulation, including high light stress (10,000 lx) and the two-stage cultivation comprising 1-aminocyclopropane-1-carboxylic acid (ACC) and FA. Under both culture conditions, the growth inhibition caused by FA was alleviated, leading to a further increase in the contents of chlorophylls and carotenoids. HPLC analysis revealed that the production of lutein, α-carotene and β-carotene increased by 0.44-, 0.37- and 0.54-fold under the treatment of 400 mg/L FA with high light intensity and 0.91-, 1.15-0.29-fold under the two-stage cultivation comprising 11 mM ACC and 500 mg/L FA. Furthermore, algal cells under FA treatment and the two-stage cultivation stained with Bodipy505/515 emitted stronger fluorescence under a laser confocal microscope, suggesting that lipid accumulation was increased. Additionally, the transcription levels of carotenogenic genes were also found to be up-regulated by qRT-PCR. These results indicated an enhancement in both the storage capacity and synthesis of carotenoids in D. bardawil. This study revealed the potential application of plant growth regulators in promoting carotenoid accumulation in D. bardawil which could be further improved by optimizing the culture conditions, providing a reference for efficient carotenoid production in microalgae., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: To analyze the risk factors and explore effective treatments for epistaxis in nasopharyngeal carcinoma (NPC) patients., Methods: From March 2006 to February 2020, 351 epistaxis patients visited our center and 195 patients meeting the inclusion criteria were enrolled in the study. Characteristics and treatments, including step-up hemostatic treatment (including medication, anterior ± posterior nostril packing, or further surgical hemostasis) and the CTPI emergency hemostasis method (including common carotid artery compression, tracheotomy / intubation, packing of nasal and nasopharynx, and interventional treatment), were analyzed., Results: The median total bleeding volume was 100.0 ml (range 20-4430 ml). 126 (64.6 %) and 69 (35.4 %) patients suffered from non-massive epistaxis and massive epistaxis. The 1-year overall survival (OS) rate was 60.1 % for patients with massive epistaxis and 97.3 % for those with non-massive epistaxis treated with step-up hemostatic treatment. Among patients with massive epistaxis, the 1-year OS rate was 80.0 % for those who received CTPI and 13.3 % for those who received step-up hemostatic treatment., Conclusion: ICA exposure and hemostasis failure was adverse prognostic factors for OS in NPC patients with epistaxis. The step-up hemostatic treatment is effective for controlling non-massive epistaxis. The CTPI emergency method might be an effective hemostasis treatment for NPC patients with massive epistaxis, especially those with PRNN and ICA exposure., 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 Ltd. All rights reserved.)

Numerous tire additives are high-production volume chemicals that are used extensively worldwide. However, their presence and partitioning behavior remain largely unknown, particularly in marine environments. This study is the first to reveal the spatiotemporal distribution, multimedia partitioning, and transport processing of 22 tire additives and their transformation products (TATPs) in a highly urbanized estuary (n = 166). Nineteen, 18, and 20 TATPs were detectable in water, suspended particulate matter (SPM), and sediments, respectively, with total levels of 59.7-2021 ng/L, 164-6935 ng/g, and 4.66-58.4 ng/g, respectively. The multimedia partitioning mechanisms of TATPs are governed by their molecular weight, hydrophobicity, and biodegradation rate. Mass inventories coupled with model simulations have revealed that substantial quantities of TATPs accumulate within estuarine environments, and these compounds can be continuously transported into the ocean, particularly during the wet season. According to the multi-criteria evaluation approach, four and three TATPs were identified as high-priority pollutants during the dry and wet seasons, respectively. Unexpectedly, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone was only listed as a medium-priority pollutant. This study underscores the importance of marine surveillance and advocates for particular attention to these ubiquitous but underexplored TATPs in future studies., 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.)

Dunaliella can accumulate more β-carotene (10 % or even more of the dry weight of cells) than any other species. Lycopene β-cyclase (LcyB) is the key enzyme in the catalysis of lycopene to β-carotene. In the present research, we used Escherichia coli BL21 (DE3) as host to construct two different types of engineering bacteria, one expressing the D. bardawil LcyB and the other expressing the orthologue Erwinia uredovora crtY. The catalytic ability of LcyB and CrtY were evaluated by comparing the β-carotene yields of the two E. coli BL21(DE3) strains, whose salt tolerance was simultaneously compared by cultivated them under different NaCl concentrations (1 %, 2 %, and 4 %). We also interfered with the LcyB gene to investigate the effect of LcyB in D. bardawil. Results displayed that the β-carotene yield of the LcyB-transformant significantly increased by about 48 % compared with the crtY-transformant. Additionally, LcyB was verified to be able to enhance the salt tolerance of E. coli BL21 (DE3). It is concluded that D. bardawil LcyB not only has better catalytic ability but also is able to confer salt tolerance to cells. Interfering D. bardawil LcyB induced the low expression of LcyB and the changes of growth and carotenoids metabolism in D. bardawil., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

p-Phenylenediamines (PPDs) and PPD-derived quinones (PPD-Qs) have been considered emerging pollutants recently. Their available data on sediment and sewage sludge are limited, especially the ecological risks. Here, typical PPDs and PPD-Qs were measured in the sludge of wastewater treatment plants and surface sediment of a developed river basin (including reservoirs, estuaries, and rivers) and deep-sea troughs. The total concentrations of PPDs (∑PPD) were highest in sludge (range: 9.06-248 ng g -1 ), followed by surface sediment of the Dongjiang River basin, China (3.33-85.3 ng g -1 ), and lowest in sediment of the Okinawa Trough (0.01-7.46 ng g -1 ). The median value of ∑PPD in surface sediment of rivers (9.54 ng g -1 ) was higher than those in reservoirs (4.28 ng g -1 ) and estuaries (5.26 ng g -1 ). N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) was the major congener in all samples, accounting for over 60 % of ∑PPD. For quinones, 6PPD-Q and IPPD-Q were frequently detected in sludge, only trace 6PPD-Q was detected in the sediment of estuaries (nd-0.62 ng g -1 ) and rivers (nd-5.24 ng g -1 ), and both of them were absent from the sediment of the Okinawa Trough. The occurrence of PPDs in the trough may be the in-situ release of microplastics, and due to the low-light and weak alkaline conditions of deep-sea water, quinones may hardly photodegrade from PPDs. The PPD concentrations in sludge were positively correlated with local GDP, and the annual PPD emission from sludge will exceed 1370 kg in China. The results of ecological risk assessments indicated low risks for PPDs in sludge-amended soil, median risks for several PPDs in river sediment, but median to high risks for 6PPD-Q contamination sludge-amended soil. For the first time, we explored the potential environmental risk of PPDs and related quinones in sludge used as a soil conditioner., 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.)

Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib-resistance. Liquid chromatography-mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD-9291, Tagrisso), H1975 cells were used to establish the osimertinib-resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and β1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV-related signaling pathway in EGFR-mutated and osimertinib-resistant lung cancer cells., (© 2024 Wiley Periodicals LLC.)

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target., (© 2024 Wiley Periodicals LLC.)

Introduction: Light-harvesting chlorophyll a/b-binding (LHCB) protein complexes of photosystem II are integral to the formation of thylakoid structure and the photosynthetic process. They play an important role in photoprotection, a crucial process in leaf development under low-temperature stress. Nonetheless, potential key genes directly related to low-temperature response and albino phenotype have not been precisely identified in tea plant. Moreover, there are no studies simultaneously investigating multiple albino tea cultivars with different temperature sensitivity., Objectives: The study aimed to clarify the basic characteristics of CsLHCB gene family members, and identify critical CsLHCB genes potentially influential in leaf color phenotypic variation and low-temperature stress response by contrasting green and albino tea cultivars. Concurrently, exploring the differential expression of the CsLHCB gene family across diverse temperature-sensitive albino tea cultivars., Methods: We identified 20 putative CsLHCB genes according to phylogenetic analysis. Evolutionary relationships, gene duplication, chromosomal localization, and structures were analyzed by TBtools; the physiological and biochemical characteristics were analyzed by protein analysis websites; the differences in coding sequences and protein accumulation in green and albino tea cultivars, gene expression with maturity were tested by molecular biology technology; and protein interaction was analyzed in the STRING database., Results: All genes were categorized into seven groups, mapping onto 7 chromosomes, including three tandem and one segmental duplications. They all own a conserved chlorophyll A/B binding protein domain. The expression of CsLHCB genes was tissue-specific, predominantly in leaves. CsLHCB5 may play a key role in the process of leaf maturation and senescence. In contrast to CsLHCB5, CsLHCB1.1, CsLHCB2, and CsLHCB3.2 were highly conserved in amino acid sequence between green and albino tea cultivars. In albino tea cultivars, unlike in green cultivars, the expression of CsLHCB1.1, CsLHCB1.2, and CsLHCB2 was down-regulated under low-temperature stress. The accumulation of CsLHCB1 and CsLHCB5 proteins was lower in albino tea cultivars. Greater accumulation of CsLHCB2 protein was detected in RX1 and RX2 compared to other albino cultivars., Conclusions: CsLHCB1.1, CsLHCB1.2, and CsLHCB2 played a role in the response to low-temperature stress. The amino acid sequence site mutation of CsLHCB5 would distinguish the green and albino tea cultivars. The less accumulation of CsLHCB1 and CsLHCB5 had a C h l influence on albino leaves. Albino cultivars more sensitive to temperature exhibited lower CsLHCB gene expression. CsLHCB2 may serve as an indicator of temperature sensitivity differences in albino tea cultivars. This study could provide a reference for further studies of the functions of the CsLHCB family and contribute to research on the mechanism of the albino in tea plant., 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 © 2023. Published by Elsevier B.V.)

Competing Interests: Prof. Anthony Y.B. Teoh is a consultant for Boston Scientific, Cook, Taewoong, Microtech and MI Tech Medical Corporations. Other authors do not have any conflicts of interest to disclose

Competing Interests: Disclosure Both authors disclosed no financial relationships. Commentary In the past decade there has been significant advancement and research to help refine endoscopic resection techniques for precancerous and cancerous GI lesions. This case highlights the importance of understanding the postresection healing process and identification of benign and malignant lesions at previous resection sites. Not all post-ESD defects heal into homogeneous and flat epithelized scars. The development of aberrant and protuberant nodules in post-ESD scars creates concern for neoplastic recurrence. After curative gastric ESD, ≤10% of scars can have a nodular or polypoid appearance, an entity described as PNS. This is more frequently observed in mucosal resections or dissections performed in the gastric antrum and may have an association with the use of histamine-2 receptor antagonists and proton pump inhibitors during the healing phase. Biopsy specimens taken from these scars show regenerative mucosa without neoplastic recurrence, and in most cases the nodular granulation tissue disappears after scarring without any long-term clinical implications. It is important for endoscopists to recognize such benign post-ESD scars and to avoid unnecessary closer follow-up care or aggressive reinterventions. Muhammad Arslan Baig, MD, Interventional Gastroenterologist, Clinical Assistant Professor of Medicine, University of Texas Health Sciences Center at Tyler, Tyler, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Ethnopharmacological Relevance: Chinese materia medica (CMM) has a long history and extensive experience in treating ischemic stroke. Wen Ezhu, the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling, is renowned for promoting blood circulation, dispersing blood stasis, alleviating pain, and eliminating masses. Promoting blood circulation and removing blood stasis are essential principles in Traditional Chinese Medicine for treating stroke. Consequently, Wen Ezhu is frequently used in clinical practice as a key CMM for treating stroke. The Elemene active fraction (ELE), a sesquiterpene compound extracted from Wen Ezhu, primarily consists of β-Elemene. It also contains β-Caryophyllene, γ-Elemene, and δ-Elemene isomers. ELE has shown potential pharmacological effects in various diseases, including ischemic stroke. However, its precise mechanism of action in treating stroke remains to be confirmed., Aim of the Study: To explore the therapeutic potential of ELE in acute ischemic stroke and elucidate its underlying mechanisms., Materials and Methods: A rat model of middle cerebral artery occlusion reperfusion (MCAO/R) was used to evaluate ELE's effects. Therapeutic efficacy was assessed through mNSS scoring, magnetic resonance imaging (MRI), tetrazolium chloride (TTC) staining, Hematoxylin and eosin (H&E), and Nissl staining. Non-targeted metabolomics identified key pathways, confirmed using biochemical analysis, immunohistochemistry, and Western blotting. ROS levels and apoptosis-related proteins were also evaluated., Results: Our findings show that ELE administration significantly reduced the cerebral infarct area and lowered modified neurological severity scores (mNSS) in animals, indicating a strong neuroprotective effect. Metabolomics results highlight the glutathione (GSH) metabolic pathway as a key mechanism through which ELE exerts its therapeutic effects. Specifically, ELE upregulates glutathione reductase (GR) protein expression and downregulates glutathione peroxidase (GPX) expression. The regulatory process of ELE decreases oxidized glutathione (GSSG) levels and increases GSH levels, effectively reducing oxidative stress damage (lower reactive oxygen species levels) during CI/RI. This results in the downregulation of the pro-apoptotic protein Bax and the upregulation of the pro-survival protein Bcl-2, thus reducing neuronal apoptosis., Conclusions: ELE protects neurons in MCAO/R rats through the GSH metabolism pathway, balancing GSH and GSSG levels to mitigate oxidative stress and enhance neuroprotection in cerebral ischemia/reperfusion injury., 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.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction and virus load in the lungs of male mice were not broadly influenced by Cxcl10 deficiency. However, accumulation of B and T lymphocytes in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19., (Published by Oxford University Press on behalf of Society for Leukocyte Biology 2024.)

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R 2  = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment., 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.)

The widespread adoption of wireless communication technology, especially with the introduction of artificial intelligence and the Internet of Things, has greatly improved our quality of life. However, this progress has led to increased electromagnetic (EM) interference and pollution issues. The development of advanced microwave absorbing materials (MAMs) is one of the most feasible solutions to solve these problems, and has therefore received widespread attention. However, MAMs still face many limitations in practical applications and are not yet widely used. This paper presents a comprehensive review of the current status and future prospects of MAMs, and identifies the various challenges from practical application scenarios. Furthermore, strategies and principles for the construction of multifunctional MAMs are discussed in order to address the possible problems that are faced. This article also presents the potential applications of MAMs in other fields including environmental science, energy conversion, and medicine. Finally, an analysis of the potential outcomes and future challenges of multifunctional MAMs are presented.

Intermittent fasting has been shown to alleviate stress, anxiety, and depressive symptoms. Although noradrenaline, also known as norepinephrine (NE), is implicated in stress regulation, the dynamics of NE release and the associated neural pathways during stress coping behaviors in fasting mice remain poorly understood. In this study, we employed the forced swimming test (FST) to evaluate the effects of intermittent fasting on stress coping behavior in mice. Our results demonstrate that mice subjected to long-term intermittent fasting exhibited significantly more active coping behaviors in the FST compared to control mice. In contrast, acute fasting did not produce similar effects. Using the fluorescent GRAB-NE sensor to measure NE release with sub-second temporal resolution during the FST, we found that intermittent fasting modulates the locus coeruleus-medial prefrontal cortex (LC-mPFC) pathway, which underlies these behavioral adaptations. Moreover, chemogenetic activation of LC-mPFC projections strongly promoted active coping in the FST. These findings suggest that enhanced LC-mPFC activity mediates the increased active coping behavior observed in fasting mice. This study provides new insights into the neural mechanisms through which intermittent fasting may ameliorate depressive-like behaviors, offering potential therapeutic targets for stress-related disorders., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical Approval: This study protocol was reviewed and approved by the Animal Care and Use Committee (Ethics No. AEC-2020025), of South China University of Technology (Guangdong, China)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Life's Essential 8 (LE8) is the American Heart Association (AHA)'s recently updated assessment of cardiovascular health (CVH). Metabolic syndrome (MetS) is one of the most common chronic noncommunicable diseases associated with CVH impairment and an increased risk of mortality. However, the association of LE8 with all-cause and disease-specific mortality in the MetS population remains unknown. We aimed to explore these associations in a national prospective cohort study from NHANES 2005-2018., Methods: The LE8 was calculated according to the assessment criteria proposed by the AHA, which includes health behavior and health factor domains. LE8 scores were categorized as low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). MetS was assessed according to NCEP-ATP III criteria, and mortality data were obtained through prospective linkage to the National Death Index database., Results: 7839 participants with MetS were included and only 3.5% were in high CVH. In the fully adjusted models, LE8 was negatively associated with both all-cause and cardiovascular disease (CVD) mortality (hazard ratios [HR] and 95% confidence intervals [CI] of 0.978 (0.971,0.984) and 0.972 (0.961,0.984), respectively, both p < 0.0001). Both moderate/high CVH were associated with significantly lower mortality compared to low CVH (both p for trend <0.0001). Health behaviors had a more dominant effect compared to health factors. All-cause and CVD mortality gradually decreased with increasing ideal LE8 metrics. LE8 was not significantly associated with cancer mortality. LE8 and health behaviors were linearly associated with all-cause and CVD mortality, whereas health factors were nonlinearly associated (plateaued after ≥50). Education and chronic kidney disease influenced the association of LE8 with all-cause and CVD mortality, respectively., Conclusions: LE8 scores were negatively associated with all-cause and CVD mortality in the MetS population, while health behaviors had a dominant role. Adherence to higher CVH contributes to the prevention of excessive all-cause and CVD mortality in the MetS population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Colchicine is a widely prescribed anti-inflammatory drug for the treatment of gout, familial Mediterranean fever and pericarditis, but its narrow therapeutic window presents a significant risk of severe toxicity. Despite its clinical relevance, the molecular mechanisms underlying colchicine's pharmacological effects and associated toxicity and explored potential therapeutic interventions to mitigate its adverse effects. We showed the colchicine's impact on cellular morphology in human umbilical vein endothelial cells (HUVEC) and HeLa cells including cell rounding and detachment following 24 h of exposure that revealed pronounced cytotoxic effects. We then established a large-scale screening model to identify small molecules capable of reversing colchicine-induced cellular toxicity, and identified MLN4924, an inhibitor of the Cullin-RING E3 ligase (CRL) system, as a promising candidate for mitigating colchicine-induced cellular injury. Through a comprehensive multi-omics approach including transcriptomics, proteomics, phosphoproteomics and ubiquitinomics, we systematically characterized the molecular perturbations caused by colchicine and delineated the protective mechanisms of MLN4924. We found that MLN4924 exerted its protective effects by modulating critical cellular pathways, specifically preventing the dysregulation of cell cycle progression, mitotic disruption and microtubule destabilization triggered by colchicine. Furthermore, proteomic and phosphoproteomic analyses revealed significant alterations in kinase signaling networks, with combined inhibition of CDK1 and PAK1 emerging as an effective strategy to counteract colchicine-induced cellular dysfunction. These results not only provide a detailed molecular characterization of colchicine toxicity but also identify key therapeutic targets, laying the groundwork for the development of targeted interventions to mitigate colchicine-induced adverse effects in clinical practice., Competing Interests: Competing interests: The patent application (ZL 2021 1 0280667.1) was filed by Min-jia Tan, Bin Liu, and Lin-hui Zhai for the novel application of MLN4924 in alleviating colchicine poisoning. All the authors in this project declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106 % with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r 2 =0.504) and NDI (r 2 =0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM., 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 and Aim: Computed tomography of the abdomen exhibits subtle and complex features of liver lesions, subjectively interpreted by physicians. We developed a deep learning-based localization and classification (DLLC) system for focal liver lesions (FLLs) in computed tomography imaging that could assist physicians in more robust clinical decision-making., Methods: We conducted a retrospective study (approval no. EMRP-109-058) on 1589 patients with 17 335 slices with 3195 FLLs using data from January 2004 to December 2020. The training set included 1272 patients (male: 776, mean age 62 ± 10.9), and the test set included 317 patients (male: 228, mean age 57 ± 11.8). The slices were annotated by annotators with different experience levels, and the DLLC system was developed using generative adversarial networks for data augmentation. A comparative analysis was performed for the DLLC system versus physicians using external data., Results: Our DLLC system demonstrated mean average precision at 0.81 for localization. The system's overall accuracy for multiclass classifications was 0.97 (95% confidence interval [CI]: 0.95-0.99). Considering FLLs ≤ 3 cm, the system achieved an accuracy of 0.83 (95% CI: 0.68-0.98), and for size > 3 cm, the accuracy was 0.87 (95% CI: 0.77-0.97) for localization. Furthermore, during classification, the accuracy was 0.95 (95% CI: 0.92-0.98) for FLLs ≤ 3 cm and 0.97 (95% CI: 0.94-1.00) for FLLs > 3 cm., Conclusion: This system can provide an accurate and non-invasive method for diagnosing liver conditions, making it a valuable tool for hepatologists and radiologists., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The role of TGF-β signaling in the epigenetic modifications involved in ovarian cancer is not fully understood. This study investigated the relationship between TGF-β signaling, epigenetic modifications, and cellular behaviors in ovarian cancer. We found that E-cadherin, a key cell adhesion molecule, underwent epigenetic silencing via promoter DNA hypermethylation in ovarian cancer cell lines and that this was accompanied by the upregulation of vimentin, which is indicative of a mesenchymal and invasive phenotype. DNA-demethylating agents restored E-cadherin expression, which suggests that TGF-β signaling mediates this epigenetic silencing. Overexpression of SMAD7, an inhibitory component of TGF-β signaling, reversed E-cadherin silencing, which suggests a role of SMAD7 in modulating the epigenetic status. Functionally, SMAD7 overexpression inhibited the migration and invasion in ovarian cancer cells, which suggests its therapeutic potential for suppressing metastasis. Clinically, ovarian cancer patients with high SMAD7 expression had significantly longer disease-free survival. Mechanistically, SMAD7 overexpression decreased the acetylation of H3K9 and the binding of the transcriptional repressor TWIST1 at the E-cadherin promoter, which promoted its demethylation and reactivation. Disruption of TGF-β signaling upregulated SMAD4 target genes, which are silenced by epigenetic mechanisms, a finding that suggests broader therapeutic implications. Overall, our results provide insights into the role of TGF-β-mediated epigenetic regulation in ovarian cancer metastasis and underscore the therapeutic potential of targeting TGF-β signaling and its downstream effectors. Further research is needed to elucidate the underlying mechanisms and validate these therapeutic strategies., (© 2024 Wiley Periodicals LLC.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only posed major health and economic burdens to international societies but also threatens patients with comorbidities and underlying autoimmune disorders, including Crohn's disease (CD) patients. As the vaccinated population is gradually relieved from the stress of the latest omicron variant of SARS-CoV-2 due to competent immune responses, the anxiety of CD patients, especially those on immunosuppressive treatment, has not subsided. Whether the use of immunosuppressants for remission of CD outweighs the potential risk of severe coronavirus disease 2019 (COVID-19) has long been discussed. Thus, for the best benefit of CD patients, our primary goal in this study was to navigate the clinical management of CD during the COVID pandemic. Herein, we summarized COVID-19 outcomes of CD patients treated with immunosuppressive agents from multiple cohort studies and also investigated possible mechanisms of how SARS-CoV-2 impacts the host immunity with special consideration of CD patients. We first looked into the SARS-CoV-2-related immunopathology, including lymphocytopenia, T-cell exhaustion, cytokine storms, and their possible molecular interactions, and then focused on mechanistic actions of gastrointestinal systems, including interruption of tryptophan absorption, development of dysbiosis, and consequent local and systemic inflammation. Given challenges in managing CD, we summarized up-to-date clinical and molecular evidence to help physicians adjust therapeutic strategies to achieve the best clinical outcomes for CD patients., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. This is a review literature. The Taipei Medical University Research Ethics Committee confirmed that no ethical approval was required. Consent for publication Not applicable.The manuscript was approved by all authors for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers., Methods: Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures., Results: Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM., Conclusion: Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets., Competing Interests: Declarations Ethics approval and consent to participate All patient data came from an institutional review board-approved studies at National Institutes of Health (NIH) (NCT00059748) and at MedImmune. Informed consent was obtained from all study participants. Consent for publication Not applicable. Competing interests K.C., M.S., and S.R. are former employees and shareholders of AstraZeneca. A.S. is a shareholder of AstraZeneca stock, and his spouse is employed by AstraZenca. A.C.S., F.M., J.L., J.W., K.C., K.S., K.Z., L.R., M.S., P.N.F., and S.R. declare no conflicts of interest., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population., Methods: The study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE)., Results: A retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3-4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population., Conclusion: This study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC., (© 2024. The Author(s).)

Background: Pruritus, a common symptom of burn wounds, arises from skin tissue damage and abnormal tissue healing. Chronic post-burn pruritus (CPBP) is defined as itching that persists for six weeks or more. The brain mechanisms underlying CPBP are not understood adequately. This study aims to explore abnormal brain function in CPBP patients and identify potential pathogenesis of pruritus., Materials and Methods: Twenty patients with CPBP and twenty healthy controls (HCs) participated in the study and underwent resting-state functional magnetic resonance imaging (fMRI) scans. Brain activity was evaluated using regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) measures. Preprocessing of fMRI data involved steps such as slice timing correction, motion correction, and nuisance regression to account for physiological noise and head motion. Statistical analyses included two-sample t-tests to compare ReHo, ALFF, and fALFF values between CPBP patients and HCs, with age as a covariate, and Spearman correlation analysis to explore relationships between brain activity measures and clinical characteristics., Results: The study revealed significant differences in brain activity between CPBP patients and HCs. CPBP patients exhibited altered higher ReHo in regions including the bilateral middle frontal gyrus, medial superior frontal gyrus, precuneus, left insula, right caudate, and bilateral cerebellar tonsils, with decreased ReHo in the right precentral gyrus. ALFF analysis showed increased activity in the bilateral middle frontal gyrus, medial superior frontal gyrus, right precuneus, and right inferior frontal gyrus, and decreased ALFF in the left precentral gyrus and right postcentral gyrus. fALFF values were notably higher in the bilateral medial superior frontal gyrus and precuneus. Several brain regions with significant differences in ReHo, ALFF, and fALFF were extensively correlated with the burned area and pruritus scale scores., Conclusion: Our data suggest that patients with CPBP show alterations in ReHo, ALFF, and fALFF values primarily in brain regions associated with the default mode network and sensorimotor areas. These results may provide valuable insights relevant to the neuropathology of CPBP., 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. Conflict of Interest The authors claim that the absence of any commercial or financial relationships that could be construed as a potential conflict of interest in this study., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Effective delivery of engineered proteins into mitochondria is of great significance for developing efficient mitochondrial DNA editing tools and realizing accurate treatment of mitochondrial diseases. Here, the candidate genes, eGFP and Cas9 , were engineered with different mitochondrial localization signal (MLS) sequences introduced at their up- or/and down-streams. The corresponding expression vectors for the engineered proteins were constructed respectively, and HEK293T cells were transfected with these vectors. The fluorescence colocalization and Western blotting assays were used to analyze the mitochondrial targeting presentation effect of different engineered proteins. The results demonstrated that the daul-MLS modification of the eGFP and Cas9 proteins significantly improved the efficiency of mitochondrial targeted presentation, compared with the engineered proteins with single MLS added. Hence, it is speculated that dual MLS strategy can enhance the mitochondrial targeting of engineered proteins, which lays a theoretical foundation for the future development of efficient mitochondrial DNA editing tools.