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Xue Li,1,&ast; Xin-Yi Tan,2,&ast; Xue-Jun Cui,3 Ming Yang,1 Chao Chen,1 Xiao-Yun Chen2 1Phase I Clinical Research Laboratory of Shanghai LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Rheumatology of Shanghai LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Institute of Spinal Disease, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Yun ChenDepartment of Rheumatology of Shanghai LongHua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725, South Wanping Road, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64289981Email lh2396@shutcm.edu.cnChao ChenPhase I Clinical Research Laboratory of Shanghai LongHua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725, South Wanping Road, Shanghai, 200032, People’s Republic of ChinaTel +86-21-64385700-9707Fax +86-21-64289981Email lhchenchao@shutcm.edu.cnBackground: Tenofovir alafenamide fumarate (TAF) was approved for HBV treatment in China in 2018. Despite higher antiviral efficacy and less impact on renal function and bone mineral density, the pharmacokinetic profiles of TAF are highly variable. The objectives of this study were to investigate the pharmacokinetics of TAF in the Chinese population and explore the associations between TAF and genetic polymorphisms and non-genetic factors.Patients and Methods: A total of 64 healthy Chinese subjects aged 18∼ 65 years old were planned to enroll. According to the dietary intake status, the subjects were divided into two groups (n = 32 per group). The concentrations of TAF and tenofovir were measured by HPLC-MS/MS, and the single-nucleotide polymorphisms were analyzed by MALDI-TOF MS.Results: All the enrolled participants (18– 35 years) completed the clinical trial study. Similar to the results reported in other ethnic populations, the pharmacokinetic profiles of TAF and tenofovir were highly variable in the Chinese people, and the HFHC diet can significantly increase the systemic exposure of TAF. We determined both HFHC diet and rs7311358 (SLCO1B3) genotypes were independently associated with TAF AUC0-t, while HFHC diet, age and rs3740066 (ABCC2) variants were predictive of t1/2 of tenofovir (P < 0.05). The subjects with the AA genotype in rs7311358 had significantly higher TAF AUC0-t values (1.15 times) than those with a G allele, and the t1/2 of tenofovir in the rs3740066 TT genotype group was 1.23 times longer than that of CC genotype group. Furthermore, there was a trend of higher TAF AUC and shorter tenofovir t1/2 for the rs2032582 (ABCB1) T allele and rs3742106 (ABCC4) CC variant, respectively, although not statistically significant in the multiple linear regression analysis.Conclusion: This study provided new evidence to suggest a critical link between both genetic and non-genetic factors and TAF pharmacokinetics in the Chinese people.Keywords: tenofovir alafenamide fumarate, pharmacokinetics, SLCO1B3, ABCB1, ABCC2, ABCC4

Allah Bukhsh,1,2 Xuan Ying Tan,1 Kok Gan Chan,3,4 Learn-Han Lee,1,2,5–8 Bey-Hing Goh,1,2,5–8 Tahir Mehmood Khan1,2 1School of Pharmacy, Monash University Malaysia, Selangor 47500, Malaysia; 2Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan; 3International Genome Centre, Jiangsu University, Zhenjiang, China; 4Division of Genetics and Molecular Biology, Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia; 5Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; 6Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia; 7Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia; 8Center of Health Outcomes Research and Therapeutic, Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Mueang Phayao, Thailand Background: Effectiveness of pharmacist-led educational interventions on self-care activities and glycemic control of type 2 diabetes mellitus (T2DM) patients is vague. The purpose of this review is to appraise the effect of pharmacist-led educational interventions on self-care activities and levels of glycated hemoglobin of T2DM patients.Methods: Five electronic databases were searched from date of database inception to September 2017. Randomized clinical trials examining the effectiveness of pharmacist-led educational interventions, directed at T2DM patients only, were included for systematic review and meta-analysis. The protocol is available with PROSPERO (CRD42017078854).Results: Eleven studies, involving n=1,544 T2DM patients, were included in this systematic review. Meta-analysis demonstrated that pharmacist-led interventions had a significant effect on lowering of the levels of glycated hemoglobin (-0.66; 95% CI [-0.83, -0.50]; I2=58.3%; P=0.008), in comparison to usual care. Self-care activities were assessed by using Summary of Diabetes Self-care Activities tool in eight studies. Overall meta-analysis of self-care activities for included studies demonstrated a significant effect of pharmacist-led interventions on improvement of self-monitoring of blood glucose (1.62; 95% CI [0.92, 2.32]; I2=70.5%; P=0.005), foot care (1.20; 95% CI [0.49, 1.90]; I2=95.0%; P

OBJECTIVE: The objective of this study was to examine the expression of cysteine-rich protein 61 (Cyr61) in the distant metastatic tumor cells of human primary salivary adenoid cystic carcinoma (SACC) and its relationship with tumor angiogensis and metastasis. STUDY DESIGN: The experimental group comprised 35 paraffin-embedded tumor specimens of distant metastasis from primary SACC, with their corresponding primary tumor tissues and matched normal salivary gland tissues used as the control groups. Immunohistochemical staining was used to detect the expression of Cyr61 and vascular endothelial growth factor in the experimental and control groups. Vascular endothelial cells were highlighted by the anti-CD34 antibody, and the Weidner method was used to quantify microvessel density (MVD). RESULTS: Cyr61 was overexpressed in distant metastatic tumor cells of primary SACC. Positive expression of Cyr61 and vascular endothelial growth factor (VEGF) progressively increased in normal salivary gland tissues, primary tumor tissues, and tumor tissues of distant metastasis (P < .05). Compared with primary tumor tissues, Cyr61 expression and VEGF expression showed significant increase in tumor tissues of distant metastasis (P < .05). Cyr61 expression significantly correlated with VEGF expression and MVD (P < .05). CONCLUSIONS: Cyr61 appeared to have a significant association with tumor angiogenesis and metastasis in SACC and may be an important target in tumor antiangiogenesis therapy. [ABSTRACT FROM AUTHOR]

The UHRF1 gene plays important roles in both cell proliferation through its NIRF_N domains, a PHD domain, an SRA domain, and a RING domain, and multidrug resistance in breast cancer treatment. In this work, a short-hairpin RNA (shRNA) lentiviral system was introduced in two human breast cancer cell lines (MDA-MB-231 and MCF-7) to downregulate the expression of UHRF1 and study the specific inhibition of UHRF1 in breast cancer growth. The effect of UHRF1-shRNA on breast cancer cell proliferation was examined using methylthiazoletetrazolium, bromodeoxyuridine, and colony formation assays. The proliferative potential of the UHRF1-shRNA-treated cells showed a remarkable decrease. Moreover, the downregulation of UHRF1 in both breast cancer cell lines significantly inhibited the colony formation capacity. Results suggested that the inhibition of UHRF1 via an RNA interference lentiviral system may provide an effective way for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Protein disulfide isomerase (PDI), a family of thiol-disulfide oxidoreductases, is one of the most abundant soluble proteins in the endoplasmic reticulum (ER) and is responsible for protein folding. Increasing evidence suggests that PDI is overexpressed in multiple types of cancer, positioning it as a promising target for tumor therapy. We have designed and synthesized a series of gallium complex-based proteolysis targeting chimeras (PROTACs), which exhibited effective targeting and degradation of PDI in vitro. After analyzing the relationship between structure and function, we have identified M-2 as the compound that most efficiently degrades PDI. Our research shows that M-2-induced degradation of PDI can trigger the unfolded protein response, leading to cell autophagy and initiating immunogenic cell death (ICD), as demonstrated in mouse models. This study suggests a potential opportunity for combining PDI targeting and immunotherapy., (© 2025 Wiley-VCH GmbH.)

The striped stem borer (Chilo suppressalis, SSB) is a highly destructive insect pest in rice (Oryza sativa). SSB oral secretions (OSs) can induce plant defense responses in rice. However, the specific effectors in SSB OSs that mediate these interactions with rice remain poorly understood. In this study, hallmarks of ferroptosis-like plant defense response, such as the reprogramming of ferroptosis-related genes, reduced glutathione levels, accumulation of ferric ion, and enhanced lipid peroxidation by reactive oxygen species (ROS), were detected in rice subjected to SSB infestation and SSB OSs treatment. Furthermore, we identified and characterized a protein from SSB OSs, the ferritin CsFer1, which plays a critical role in the regulation of plant iron homoeostasis. CsFer1 was shown to possess Fe 2+ binding capacity and ferroxidase activity. Through recombinant CsFer1 protein treatment, overexpression of CsFer1 in rice and SSB larvae with silencing CsFer1 feeding in rice, we found that CsFer1 helped maintain iron homoeostasis under SSB infestation, suppressing H 2 O 2 and JA accumulation, ultimately compromising rice resistance to herbivorous pests. Moreover, such a phenomenon about the regulation of iron homoeostasis and suppression of insect resistance was observed in the CsFer1 overexpressed tobacco. Collectively, these findings suggest that CsFer1 functions as an effector involved in the regulation of iron homoeostasis- and lipid peroxidation-related plant defense during plant-insect interaction., (© 2025 John Wiley & Sons Ltd.)

Sb 2 Si 2 Te 6 is a promising 2D material for medium-temperature thermoelectric applications, with the thermoelectric figure of merit zT approaching 1 at 823 K. However, its widespread use has been limited by relatively low power factor values. In this study, we successfully enhanced the performance of Sb 2 Si 2 Te 6 by introducing Yttrium nanocomposites. This modification fine-tuned the carrier concentration and electrical conductivity, and increased the power factor up to 946 μW K -1 at 570 K. Jonker plot analysis revealed that increased carrier concentration did not affect the intrinsic electronic properties. SEM and TEM analyses revealed that Y nano-compositing introduced secondary phases, reducing the lattice thermal conductivity to values close to simulated ones using the Debye-Callaway model. Sb 1.98 Y 0.02 Si 2 Te 6 exhibited the highest zT of 1.49 at 773 K due to the ultralow lattice thermal conductivity of 0.29 W m -1 K -1 and a moderate power factor of 858 μW K -1 at the same temperature. The single parabolic band (SPB) model suggests that with further optimization of the Fermi level and additional reduction in lattice thermal conductivity, the zT value could potentially increase to 1.55. These results demonstrate the potential of Y nanocompositing for enhancing Sb 2 Si 2 Te 6 as an efficient medium-temperature thermoelectric material.

Mucormycosis is a rare but fatal opportunistic fungal infection. Patients with hematologic malignancies who use immunosuppressant and glucocorticoid extensively are susceptible to mucormycosis. We report a case of an older patient with acute myeloid leukemia (AML) who was infected with pulmonary mucormycosis during chemotherapy. With a good balance of chemotherapy-induced myelosuppression and control of Mucorales infection, the patient got a complete remission of leukemia by the combination of azacitidine and venetoclax, and pulmonary mucormycosis was well controlled. But due to poor compliance, the patient died of asphyxiation as a result of aspiration of pulmonary necrosis-like substances after discharge. To our knowledge, this is the first case report of an older patient with AML complicated with pulmonary mucormycosis dying of asphyxia from pulmonary necrosis-like substances. Our article seeks to raise awareness of proper precautions to be taken in the management mucormycosis., Competing Interests: The authors have no conflict of interest to report., (Copyright 2025, Luo et al.)

Background: Mobile health (mHealth) interventions have gained popularity in augmenting psychiatric care for adults with psychosis. Interest has grown in leveraging mHealth to empower individuals living with severe mental illness and extend continuity of care beyond the hospital to the community. However, reported outcomes have been mixed, likely attributed in part to the intervention and adopted outcomes, which affected between-study comparisons., Objective: This study aimed to critically review outcome measures used to evaluate mHealth interventions for adults with psychosis in relation to the characteristics of mHealth interventions., Methods: A systematic mapping review was conducted. We searched PubMed, CINAHL, Embase, PsycINFO, and Cochrane Libraries from 1973 to the present. Selection criteria included randomized controlled studies of mHealth interventions in adults diagnosed with schizophrenia spectrum disorders. Reviewers worked in pairs to screen and extract data from included studies independently using a standardized form; disagreements were resolved by consensus with an independent reviewer. We report our findings in line with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines., Results: A total of 1703 citations were screened; 29 publications reporting on 23 studies were included in this review. mHealth interventions for psychosis span a wide range, with psychological therapy being the most-deployed intervention (12/23, 52%), followed by psychoeducation (8/23, 35%) and active self-monitoring (8/23, 35%). Several mHealth interventions for psychosis targeted multiple pillars of biopsychosocial well-being (10/23, 43%); the bulk of interventions (16/23, 70%) incorporated features promoting users' self-management. The majority of mHealth interventions were delivered through applications (14/23, 61%) as the main medium and smartphones (17/23, 74%) as the main channel of delivery. Interventions were primarily administered in the outpatient and community settings (16/23, 70%); many were also blended with in-person sessions (11/23, 48%) or guided remotely (6/23, 26%) by persons, including health care providers or trained peer supporters. The severity of psychosis-related symptoms (21/23, 91%) was the most prevalent outcome, of which positive symptoms (13/23, 57%), mood and anxiety (10/23, 43%), and overall psychopathology severity (9/23, 39%) were most commonly measured. Patient-centric outcomes, including well-being (17/23, 74%)-particularly quality of life (10/23, 43%)-and user experience (15/23, 65%), including feasibility (7/23, 30%), acceptability (7/23, 30%), and engagement (7/23, 26%). Notably, outcome choices remained diverse despite stratification by type of mHealth intervention., Conclusions: mHealth interventions for psychosis encompass a wide range of modalities and use outcome measures that probe various social and behavioral determinants of health. These should be considered complex interventions, and a holistic evaluation approach combining clinical and patient-centric outcomes is recommended., (©Pei Yi Loh, Laura Martinengo, Creighton Heaukulani, Xin Yang Tan, Moses Hng, Yong Yin Cheah, Robert J T Morris, Lorainne Tudor Car, Jimmy Lee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.12.2024.)

Background: Mentoring's success in nurturing professional identity formation (PIF) has been attributed to its ability to build personalised and enduring mentoring relationships. However, beyond functioning as communities of practice (CoPs) supporting socialisation processes, how mentoring integrates programme values and instils a shared identity amongst mentees remains unclear. The need for personalised guidance and timely attention to a mentee's unique needs in evolving mentoring relationships point to the critical role of support mechanisms ('mentoring support'). We conducted a systematic scoping review (SSR) studying "What is known about mentoring support's role in nurturing PIF?"., Methods: Adopting PRISMA-ScR guidelines, this SSR was guided by the Systematic Evidence-Based Approach (SEBA). Independent searches were carried out on publications featured between 1st January 2000 and 30th June 2023 in PubMed, Embase, ERIC and Scopus databases. The Split Approach saw concurrent, independent thematic and content analyses of the included articles. The Jigsaw Perspective combined complementary themes and categories, creating broader themes/categories. The subsequent Funnelling Process formed key domains that platformed the synthesis of the discussion., Results: Two thousand three hundred forty-one abstracts were reviewed, 323 full-text articles were appraised and 151 articles were included and analysed. The key domains identified were (1) definitions and roles; (2) personalisation; (3) shepherding; and (4) PIF., Conclusion: The success of mentoring in PIF lies in its ability to blend role modelling, supervision, mentoring, coaching and teaching, with self-care, guided reflection, apprenticeship and assessment to meet the individual needs of the mentee and their changing circumstances. Blending the contents of the mentoring umbrella emphasises the critical role of the mentor and host organisation in supporting mentor training, communications, support and assessment mechanisms. Mentee engagement and its active role in support measures complement the CoP-like mentoring programme's use of blending mentoring support to advance the socialisation process. These insights reflect a complex interactive process scaffolding the development of mentoring relationships and PIF. The effect of the mentoring umbrella on clinical practice requires further study., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Aplastic anaemia (AA) is a rare disorder of bone marrow failure, characterized by bone marrow hypocellularity with pancytopenia. The annual incidence rates of AA in Asia are observed to be two to three times higher than Europe and North America. Since the introduction of immunosuppressive therapy (IST) and of allogenic stem cell transplant (SCT), the outcome of severe AA has significantly improved. We conducted a 12-year multi-centre retrospective study among the adult AA population in Sabah and Sarawak., Materials and Methods: A total of 119 AA patients had been identified from hospital records of the involved sites, namely Queen Elizabeth Hospital in Sabah, Sarawak General Hospital, Sibu Hospital, Miri Hospital and Bintulu Hospital in Sarawak from Jan 2006 to Dec 2017., Results: The median age at diagnosis was 46 years, and native ethnic group from Sabah, Kadazan-Dusun, recorded the highest percentage of 41.2%, which could be explained by higher frequency of HLA-DRB1*15:01, an alelle linked to increased risk of AA, among this ethnic group. The majority of patients (59.7%) received cyclosporine (CsA) as monotherapy or in combination with other non-IST agents such as danazol, which was instituted in 48.7% of the patients, while a third of them (33.7%) received antithymocyte globulin (ATG) therapy with or without CsA, and 12.4% underwent allogenic SCT. The five-year overall survival (OS) for all AA patients was 76.1%. Elderly patients >60 years old and those with severe disease had more inferior 5-year survival., Conclusion: A prospective study is warranted to determine the true incidence rate, epidemiological distributions, treatment outcome and overall survival of AA patients in Malaysia. Establishment of allogenic SCT in East Malaysia is imperative to make this curative therapy more accessible to patients with severe disease and improve the outcome.

The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (znt4, znt5 and znt10) in Zn 2+ metabolism in yellow catfish (Pelteobagrus fulvidraco), commonly freshwater fish in China and other countries. We cloned the sequences of znt4 promoter, spanning from -1217 bp to +80 bp relative to TSS (1297 bp); znt5, spanning from -1783 bp to +49 bp relative to TSS (1832 bp) and znt10, spanning from -1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (-607/-621 bp) and Klf4 binding site (-5/-14 bp) were required on znt4 promoter, the Mtf-1 binding site (-1674/-1687 bp) and Atf4 binding site (-444/-456 bp) were required on znt5 promoter and the Atf4 binding site (-905/-918 bp) was required on znt10 promoter. Then, according to EMSA and ChIP, we found that Zn 2+ incubation increased DNA affinity of Atf4 to znt5 or znt10 promoter, but decreased DNA affinity of Nrf2 to znt4 promoter, Klf4 to znt4 promoter and Mtf-1 to znt5 promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that znt4 knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; znt5 knockdown reduced the zinc content of Golgi in the control and zinc-treated group and znt10 knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of znt4 promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of znt5 promoter and Atf4 transcriptionally regulated the activities of znt10 promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish., Competing Interests: Declaration of competing interest The authors declared 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.)

Objective: To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury., Methods: From January 2016 to December 2020, the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed, including 35 males and 22 females, aged from 18 to 47 years old with an average of (32.9±7.9) years old. Knee function was evaluated using the International Knee Documentation Committee (IKDC) and Lysholm scores both before the operation and at the final follow-up. Meniscus healing was evaluated according to the postoperative Barrett standard. Wound healing complications, such as vascular injury, nerve injury, and lower extremity venous thrombosis, were recorded., Results: All 57 patients were followed up for 12 to 58 months with an average of (38.1±14.9) months.The incisions of the patients after the operation were all Grade A healing without infection, popliteal tendon injury, blood vessel injury, nerve injury and lower extremity venous thrombosis.The IKDC score increased from (49.7±3.6) points preoperatively to (88.5±4.4) points in the final follow-up ( P <0.05). The Lysholm score increased from (48.8±4.9) points preoperatively to (91.9±3.9) points at the final follow-up ( P <0.05). At 3, 6 months and 1 year after operation, according to Barrett's criteria, 54 cases were clinically healed, the healing rate was 94.7% (54/57)., Conclusion: This study preliminarily confirmed that arthroscopic suture technique can result in clinical stability through suture and fixation of the meniscus in the injured lateral popliteal tendon area. No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC., Competing Interests: Declaration of interests W.-Z.Z.. received speech honoraria from AstraZeneca, Roche, Eli Lilly, and Pfizer outside the submitted work. Z.-M.Z. is a founder of Analytical BioSciences. Y.-L.W. received research funding from Roche and speech honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi, and he was a research consultant for AstraZeneca. Q.Z. reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

GeSe, an analogue of SnSe, shows promise in exhibiting exceptional thermoelectric performance in the Pnma phase. The constraints on its dopability, however, pose challenges in attaining optimal carrier concentrations and improving ZT values. This study demonstrates a crystal structure evolution strategy for achieving highly doped samples and promising ZT s in GeSe via LiBiTe 2 alloying. A rhombohedral phase ( R 3 m ) can be stabilized in the GeSe-LiBiTe 2 system, further evolving into a cubic ( Fm 3 ̅m ) phase with a rising temperature. The band structures of GeSe-LiBiTe 2 in the rhombohedral and cubic phases feature a similar multiple-valley energy-converged valence band of L and Σ bands. The observed high carrier concentration (∼10 20 cm -3 ) reflects the effective convergence of these bands, enabling a high density-of-states effective mass and an enhanced power factor. Moreover, a very low lattice thermal conductivity of 0.6-0.5 W m -1 K -1 from 300 to 723 K is achieved in 0.9GeSe-0.1LiBiTe 2 , approaching the amorphous limit value. This remarkably low lattice thermal conductivity is related to phonon scattering from point defects, planar vacancies, and ferroelectric instability-induced low-energy Einstein oscillators. Finally, a maximum ZT value of 1.1 to 1.3 at 723 K is obtained, with a high average ZT value of over 0.8 (400-723 K) in 0.9GeSe-0.1LiBiTe 2 samples. This study establishes a viable route for tailoring crystal structures to significantly improve the performance of GeSe-related compounds.

Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer., (© 2024. The Author(s).)

N 6 -methyladenosine (m 6 A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m 6 A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m 6 A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m 6 A modifications against RSB. Upon RSB infestation, m 6 A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m 6 A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m 6 A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m 6 A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride-based alloys are still the best for near-room-temperature applications. In this work, a ≈38% enhancement of the average ZT (300-473 K) to 1.21 is achieved by mixing Bi 0.4 Sb 1.6 Te 3 with an emerging thermoelectric material Sb 2 Si 2 Te 6 , which is significantly higher than that of most Bi y Sb 2-y Te 3 -based composites. This enhancement is facilitated by the unique interface region between the Bi 0.4 Sb 1.6 Te 3 matrix and Sb 2 Si 2 Te 6 -based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high-density dislocations in the same region can effectively scatter the phonons, decoupling the electron-phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single-leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb 2 Si 2 Te 6 compositing strategy and the importance of the precipitate-matrix interface microstructure in improving the performance of materials for relatively low-temperature applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95% CI : 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [ M ( Q 1 , Q 3 )] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group ( n =122) and high T4-SMD group ( n =54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95% CI : 9.3-11.8) vs 13.7 (95% CI : 11.1-18.5) months, 36.1% vs 59.3%, respectively, P =0.034]. Eastern Cooperative Oncology Group performance status ( HR =3.308, 95% CI : 1.183-9.247, P =0.023), lactate dehydrogenase level ( HR =1.852, 95% CI : 1.037-3.307, P =0.037), systemic immune-inflammation index ( HR= 1.772, 95% CI : 1.019-3.080, P =0.043), and T4-SMD ( HR =0.563, 95% CI : 0.325-0.974, P =0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95% CI : 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

Topological phases in kagome systems have garnered considerable interest since the introduction of the colloidal kagome lattice. Our study employs first-principle calculations and symmetry analysis to predict the existence of ideal type-I, III nodal rings (NRs), type-I, III quadratic nodal points (QNPs), and Dirac valley phonons (DVPs) in a collection of two-dimensional (2D) kagome lattices M 2 C 3 (M = As, Bi, Cd, Hg, P, Sb, Zn). Specifically, the Dirac valley points (DVPs) can be observed at two inequivalent valleys with Berry phases of + π and-π, connected by edge arcs along the zigzag and armchair directions. Additionally, the QNP is pinned at the Γ point, and two edge states emerge from its projections. Notably, these kagome lattices also exhibit ideal type-I and III nodal rings protected by time inversion and spatial inversion symmetries. Our work examines the various categories of nodal points and nodal ring phonons within the 2D kagome systems and presents a selection of ideal candidates for investigating topological phonons in bosonic systems., (© 2024 IOP Publishing Ltd.)

Introduction: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak., Materials and Methods: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited., Results: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01)., Conclusion: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

Background: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China., Methods: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist., Results: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05)., Conclusion: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy., Trial Registration: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn., (© 2024. The Author(s).)

In this study, an advanced ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed for quantifying ethoxyquin (EQ). The approach employed a distinctive antioxidant added extraction step designed to prevent ethoxyquin decomposition and maintain analytical precision. This method effectively determines residue levels of EQ in eggs, processed egg products, poultry muscle, salmon, and liquid milk. The method was shown to have a limit of quantitation (LOQ) for eggs, milk, salmon, and chicken muscle of 1.5 µg/kg, 1.9 µg/kg, 2.1 µg/kg, and 1.2 µg/kg, respectively. The recoveries of EQ ranged from 79.2% to 107.6%, with a relative standard deviation (RSD) below 8.4%. A surveillance study for the presence of EQ in different types of eggs and poultry muscle available in Singapore was conducted and a total of 140 samples were tested. EQ residues in all samples were found to be below the U.S. Food and Drug Administration (FDA) MRLs of 500 µg/kg. Some samples of salted and preserved eggs from China were detected with higher concentration of EQ.

SREBPs, such as SREBP1 and SREBP2, were the key transcriptional factors regulating lipid metabolism. The processing of SREBPs involved many genes, such as scap, s1p, s2p, cideb. Here, we deciphered the full-length cDNA sequences of scap, srebp1, srebp2, s1p, s2p, cideb and cidec from yellow catfish Pelteobagrus fulvidraco. Their full-length cDNA sequences ranged from 1587 to 3884 bp, and their ORF length from 1191 to 2979 bp, encoding 396-992 amino acids. Some conservative domains were predicted, including the multiple transmembrane domains in SCAP, the bHLH-ZIP domain in SREBP1 and SREBP2, the ApoB binding region, ER targeting region and LD targeting region in CIDEb, the LD targeting region in the CIDEc, the conserved catalytic site and processing site in S1P, and the transmembrane helix domain in S2P. Their mRNA expression could be observed in the heart, spleen, liver, kidney, brain, muscle, intestine and adipose, but varied with tissues. The changes of their mRNA expression in responses to high-fat (HFD) and bile acid (BA) diets were also investigated in the brain, heart, intestine, kidney and spleen tissues. In the brain, HFD significantly increased the mRNA expression of seven genes (scap, srebp1, srebp2, s1p, s2p, cideb and cidec), and the BA attenuated the increase of scap, srebp1, srebp2, s1p, s2p, cideb and cidec mRNA expression induced by HFD. In the heart, HFD significantly increased the mRNA abundances of six genes (srebp1, srebp2, scap, s2p, cideb and cidec), and BA attenuated the increase of their mRNA abundances induced by HFD. In the intestine, HFD increased the cideb, s1p and s2p mRNA abundances, and BA attenuated the HFD-induced increment of their mRNA abundances. In the kidney, HFD significantly increased the scap, cidec and s1p mRNA expression, and BA diet attenuated the increment of their mRNA expression. In the spleen, HFD treatment increased the scap, srebp2, s1p and s2p mRNA expression, and BA diet attenuated HFD-induced increment of their mRNA expression. Taken together, our study elucidated the characterization, expression profiles and transcriptional response of seven lipid metabolic genes, which would serve as the good basis for the further exploration into their function and regulatory mechanism in fish., 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 Elsevier B.V. All rights reserved.)

Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC 50 values were 4.7 and 6.4 μM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg -1 ·d -1 , i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The animal and cell models were used in this study to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in inhibiting colon cancer progression and enhancing the efficacy of 5-fluorouracil(5-FU) by regulating hypoxia-inducible factors and tumor stem cells. The animal model was established by subcutaneous transplantation of colon cancer HCT116 cells in nude mice, and 24 successfully modeled mice were randomized into model, 5-FU, HQEZ, and 5-FU+HQEZ groups. The tumor volume was measured every two days. Western blot was employed to measure the protein levels of epidermal growth factor receptor(EGFR), dihydropyrimidine dehydrogenase(DPYD), and thymidylate synthase(TYMS), the key targets of the hypoxic core region, as well as the hypoxia-inducible factors HIF-1α and HIF-2α and the cancer stem cell surface marker CD133 and SRY-box transcription factor 2(SOX2). The results of animal experiments showed that HQEZ slowed down the tumor growth and significantly increased the tumor inhibition rate of 5-FU. Compared with the model group, HQEZ significantly down-regulated the protein levels of EGFR and DPYD, and 5-FU+HQEZ significantly down-regulated the protein levels of EGFR and TYMS in tumors. Compared with the model group, HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, SOX2, and CD133 in the hypoxic core region. Compared with the 5-FU group, 5-FU+HQEZ lowered the protein levels of HIF-1α, HIF-2α, and SOX2. The cell experiments showed that the protein le-vels of HIF-1α and HIF-2α in HCT116 cells elevated significantly after low oxygen treatment. Compared with 5-FU(1.38 μmol·L~(-1)) alone, HQEZ(40 mg·mL~(-1)) and 5-FU+HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, and TYMS. In conclusion, HQEZ can inhibit the expression of hypoxia-responsive molecules in colon cancer cells and reduce the properties of cancer stem cells, thereby enhancing the therapeutic effect of 5-FU on colon cancer.

Ethnopharmacological Relevance: The herbal pair of Trichosanthis Pericarpium (TP) - Trichosanthis Radix (TR) can be seen in the famous formula "Beimu Gualou San". It is a commonly selected combination of medicinal herbs for the treatment of cough with lung heat. Both drugs are derived from Trichosanthes kirilowii Maxim, a medicinal plant known for its ability to clear heat, resolve phlegm, produce saliva, and alleviate dryness. However, the optimal combination ratio and active ingredients of TP-TR have yet to be determined., Aim of the Study: This study aims to investigate the optimal combination ratio of TP-TR and its anti-inflammatory active ingredients in cough treatment., Materials and Methods: A zebrafish (Danio rerio) inflammatory injury model and response surface method were applied in the present study to determine the appropriate proportion of TP-TR. Chemical constituents in TP-TR were identified using HPLC-ELSD and UPLC-MS/MS methods. Subsequently, a cough mouse model was created using an ammonia solution to evaluate the effectiveness of the optimal TP-TR ratio. Network pharmacology and intestinal flora sequencing were used to validate the anti-inflammatory components of TP-TR., Results: The herbal pair of TP - TR at the ratio of 1:2 showed an optimal anti-inflammatory effect, with a composite inflammatory factor score of 119.645 in the zebrafish experiment. TP-TR combination facilitated the dissolution of glutamine, inosine, cytosine, isoquercetin, and other substances. In the animal model, the TP-TR (1:2) treatment significantly reduced the frequency of coughs and prolonged cough latency compared to the model group. Results of the network pharmacology indicated that inflammatory-related factors such as TLR4, STAT3, EGFR, and AKT1 played crucial roles in cough treatment with TP-TR, consistent with the validation experiment. The 16s rDNA sequencing results revealed a significant increase in the abundance of Clostridia&#95;UCG-014, Lachnospiraceae, Christenella, Ruminococcus, and other species in the intestinal tract of mice after modelling. TP-TR (1:2) reduced the abundance of pro-inflammatory flora such as Clostridium&#95;UCG-014 and Lachnospira, which were closely associated with L-lysine and trans-4-hydroxy-L-proline present in TP-TR according to correlation analysis., Conclusion: TP-TR may promote the dissolution of glutamine, thymidine, inosine, cytosine, isoquercetin, and other components through their combination, thereby regulating the abundance of Clostridium&#95;UCG-014 and Lachnospira and exerting an antitussive effect. This study, for the first time, showed that TP-TR at a 1:2 ratio exhibits superior anti-inflammatory effects. In addition to inflammatory mediators like EGFR, TLR4, AKT1, and STAT3, gut microbes could also serve as potential regulatory targets of TP-TR in the treatment of cough. 2'-Deoxyguanosine monohydrate, L-lysine, L-leucine, γ-aminobutyric acid, L-valine, L-tryptophan, L-proline, trans-4-hydroxy-L-proline, L-methionine, uridine, 2'-deoxyinosine, guanosine, cucurbitacin B and cucurbitacin D were identified as its anti-inflammatory active ingredients., 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 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients., Methods: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation., Results: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group., Conclusions: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

A stable anode-free lithium metal battery (AFLMB) is accomplished by the adoption of a facile fabricated amorphous antimony (Sb)-coated separator (SbSC). The large specific surface area of the separator elevates lithium (Li)-Sb alloy kinetic, improving Li wetting ability on pristine copper current collector (Cu). When tested with LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811) as cathode, the full cell with SbSC demonstrates low nucleation overpotential with compact, dendrite-free and homogeneous Li plating, and exhibits a notable lithium inventory retention rate (LIRR) of 99.8 % with capacity retention of 93.6 % after 60 cycles at 0.5 C-rate. Conversely, full cells containing pristine separator/Cu (i. e., SC) and pristine separator/Sb-coated current collector (i. e., SSbC) display poor cycling performances with low LIRRs. Density functional theory corroborates the nucleation behaviours observed during in-situ half-cell Li deposition. Functionalizing polymeric separator by metallic coating in AFLMB is a novel approach in improving the cycle life of an AFLMB by promoting homogeneous Li plating behavior. This innovative approach exemplifies a promising applicability for uniform Li-plating behavior to achieve a longer cycle life in AFLMB., (© 2023 Wiley-VCH GmbH.)

Understanding the hazards of different forms of metal elements provided innovative insights into their toxicity and environmental risk assessment. To date, few studies had been conducted to investigate the differential effects and mechanisms of MnO 2 NPs and MnSO 4 , two widely distributed environmental pollutants, on hepatic toxicity and lipid metabolism since lipid metabolism-relevant parameters were broadly used as biomarkers for risk assessment of hazardous contaminants. Thus, using yellow catfish Pelteobagrus fulvidraco, an ecologically and economically important freshwater fish as the model, the present study investigated the differential effects and mechanisms of MnO 2 NPs and MnSO 4 influencing hepatic lipid metabolism. Compared to MnSO 4 , MnO 2 NPs increased hepatic Mn content, induced lipotoxicity, up-regulated the mRNA expression of lipogenic genes, increased peridroplet mitochondrial (PDM) contents, intensified the contact between mitochondria and lipid droplets (LDs), and downregulated miR-20a-5p abundance. Importantly, miR-20a-5p targeted mfn2, which mediated the contact between mitochondria and LDs and influenced changes in lipid metabolism induced by MnO 2 NPs. Mechanistically, the direct Mfn2-Plin2 binding and Mfn2 GTPase activity promoted the MnO 2 NPs-induced interactions between mitochondria and LDs, which in turn influenced MnO 2 NPs-induced changes in hepatic lipid metabolism. For the first time, our findings indicated the significant differences between the changes in body metabolism induced by nanoparticles and inorganic elements, which helped to illuminate different mechanisms governing the responses of aquatic vertebrates to hazardous metal pollutants (MnO 2 NPs and MnSO 4 )., 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 Elsevier B.V. All rights reserved.)

In this study, two novel bacterial strains were isolated from coastal sediment of Weihai, China. The two strains were Gram-stain-negative and facultatively aerobic, designated 3-1745 T and A346 T . Based on phenotypic, genetic and phylogenetic properties, strains 3-1745 T and A346 T represent two novel species of the genus Marinobacterium . The results of genome analysis revealed many central carbohydrate metabolism pathways such as gluconeogenesis, pyruvate oxidation, tricyclic acid cycle, pentose phosphate pathway and PRPP biosynthesis in the genus Marinobacterium . The ability of strains 3-1745 T and A346 T to utilize volatile fatty acids was experimentally confirmed. Polyhydroxyalkanoate synthases (PhaA, PhaB and PhaC) for the synthesis of polyhydroxyalkanoates were prevalent in the genus Marinobacterium . Multiple BGCs (biosynthetic gene clusters) including betalactone, ectoine, ranthipeptide, redox-cofactor, RiPPs (ribosomally synthesized post-translationally modified peptides) and T3PKS (polyketide synthases) in the genome of the genus Marinobacterium were found. Additional genome analyses suggested that the genus Marinobacterium contained diverse potential mechanisms of salt tolerance and mainly utilized oligosaccharides. This is the first report on broad genomic analyses of the genus Marinobacterium with the description of two novel species and potential ecological and biotechnological implications.

Metabolic stress induces lipophagy, a crucial process in lipid catabolism, which is under the regulation of autophagy involving transcription factor EB (TFEB). However, the precise mechanisms underlying TFEB's control remain enigmatic. In this study, we focused on yellow catfish (Pelteobagrus fulvidraco) as the model to investigate lipophagy activation under high glucose-induced lipid deposition. We hypothesized that lipophagy mediates high glucose-induced lipid deposition and proposed the involvement of the SIRT1-NRF2-TFEB pathway in the activation of lipophagy. We found that there was a functional antioxidative responsive element (ARE) on the tfeb gene promoter; high glucose (HG) increased the nuclear translocation of nuclear factor E2-related factor 2 (NRF2) recruitment to the tfeb promoter; TFEB, whose expression is regulated by NRF2, mediated the HG-induced activation of lipophagy and lipolysis. Moreover, we found that HG increased the silencing information regulator 2 related enzymes 1 (SIRT1) expression, and that the SIRT1 mediates NRF2 translocation to the nucleus, increased TFEB expression and activated autophagy. In the glucose tolerance test, blood glucose increased rapidly and plateaued at 4-h glucose after injection and then declined until 48-h post-injection. Generally speaking, the transcript level and protein expression of SIRT1, NRF2, TFEB, microtubule-associated proteins 1A/1B light chain 3B (LC3B), and autophagy-related 6 (Beclin1) showed similar trend after glucose injection, and trends to increase and plateau at 4-h injection, then decline until 16-h post-injection, and finally increased until 48-h post-injection. These results indicated that the SIRT1-NRF2-TFEB axis-mediated lipophagy may be an adaptive response to glucose injection. Collectively, for the first time, we found that NRF2 was associated directly with TFEB-mediated transcriptional control of hepatic lipophagy, and that lipophagy helps to alleviate the HG-induced lipid deposition via SIRT1-NRF2-TFEB activation in yellow catfish., Competing Interests: Declaration of Competing Interest No conflict of interest was declared by authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Iron is an essential metal element for organisms, whose metabolism is regulated by many genes and also dietary iron sources. However, the characterization, distribution and the responses of iron metabolism-related genes to different iron sources were not clear in fish., Methods: The full-length cDNA sequences of fifteen iron metabolism-relevant genes (tf, tfr1, hp, fpn1, ho1, ho2, tfr2, hjv, hepcidin, fth, ftl, ftm, irp1, irp2 and hif2α.) were obtained via 3' and 5' RACE PCR from yellow catfish, a widely distributed freshwater teleost in China and other Asian countries. Their molecular characterizations were analyzed via the bioinformatic methods. Real-time quantitative PCR was used to explore their mRNA distribution in nine tissues. Their mRNA expression responses in four tissues (heart, brain, kidney and gill) were explored in yellow catfish fed diets with five iron sources, including ferrous sulfate (FeSO 4 ), ferrous bisglycinate (Fe-Gly), ferrous chloride (FeCl 2 ), ferric citrate (Fe-CA) and ferric oxide nanoparticles (Fe 2 O 3 NPs)., Results: Compared with mammals and other teleost, these members shared similar domains. Their mRNAs were expressed in nine tested tissues, but mRNA levels varied. Yellow catfish fed the diets containing Fe-Gly and Fe 2 O 3 NPs had higher iron contents in heart, brain, kidney and gill. Meantime, different dietary iron sources addition affected their mRNA expression differentially in brain, heart, kidney and gill. It should be pointed out that only three biological replicate tanks were used in the present feeding treatment, and more biological replicate tanks (more than five) should be emphasized in further researches., Conclusion: Taken together, our study identified fifteen iron metabolism-relevant genes, explored their mRNA expression in nine tissues, and their mRNA expression in the responses to different dietary iron sources in four tissues, indicating their important regulatory function in iron metabolism and homeostasis., 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 Elsevier GmbH. All rights reserved.)

Background: Laparoscopic pancreaticoduodenectomy(LPD) has become the goal of lots of minimally invasive surgical centers in recent years. Postoperative pancreatic fistula(POPF) is still the barrier to attaining the above goal. Thus, improving anastomosis techniques to reduce the rate of POPF has been a hotspot of surgery. Blumgart pancreaticojejunostomy is considered one of the best anastomosis procedures, with low rates of POPF. However, the original Blumgart pancreaticojejunostomy method is not easy for laparoscopic operation. In consequence, we modified a Blumgart pancreaticojejunostomy technique with a simple and practicable procedure and applied to LPD., Methods: We collected and retrospectively analyzed the perioperative clinical data of patients who underwent modified Blumgart anastomosis from February 2017 to September 2022. The above patients included 53 cases in open pancreaticojejunostomy(OPD) and 58 cases in LPD. After propensity score matching, 44 cases were included for comparison in each group., Results: After propensity score matching, the average time for pancreaticojejunostomy was about 30 min in the LPD group. The Clinically relevant POPF(CR-POPF) rate was 9.1%. The length of postoperative hospitalization was 13.1 days. Compared with the OPD group, The CR-POPF rate in the LPD group are not significant differences. But the postoperative length of hospital stay was significantly shorter in the LPD group. Besides, there were no other severely postoperative complications between two groups., Conclusion: The modified Blumgart anastomosis technique applied to LPD in our Center not only has simple and convenient properties but also low rate of CR-POPF. And this method may be a good choice for surgeons to begin to carry out LPD., (© 2023. The Author(s).)

Enrofloxacin (ENR) is a kind of widespread hazardous pollutant on aquatic ecosystems and causes toxic effects, such as disorders of metabolism, on aquatic animals. However, its potential mechanisms at an environmental concentration on metabolic disorders of aquatic organisms remain unclear. Herin, we found that hepatic lipotoxicity was induced by ENR exposure, which led to ENR accumulation, oxidative stress, mitochondrial fragmentation, and fatty acid transfer blockage from lipid droplets into fragmented mitochondria. ENR-induced lipotoxicity and mitochondrial β-oxidation down-regulation were mediated by reactive oxygen species (ROS). Moreover, dynamin-like protein 1 (DRP1) mediated ENR-induced mitochondrial fragmentation and changes of lipid metabolism. Mechanistically, ENR induced increment of DRP1 mitochondrial localization via dephosphorylating DRP1 at S627 and promoted its interaction with mitochondrial fission factor (MFF), leading to mitochondria fragmentation. For the first time, our study provides an innovative mechanistic link between hepatic lipotoxicity and mitochondrial fragmentation under ENR exposure, and thus identifies previously unknown mechanisms for the direct relationship between environmental ENR concentration and lipotoxicity in aquatic animals. Our study provides innovative insights for toxicological mechanisms and environmental risk assessments of antibiotics in aquatic environment., 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 Elsevier Ltd. All rights reserved.)

Zinc (Zn) is a multipurpose trace element indispensable for vertebrates and possesses essential regulatory roles in lipid metabolism, but the fundamental mechanism remains largely unknown. In the current study, we found that a high-Zn diet significantly increased hepatic Zn content and influenced the expression of Zn transport-relevant genes. Dietary Zn addition facilitated lipolysis, inhibited lipogenesis, and controlled β-catenin signal; Zn also promoted T-cell factor 7-like 2 (TCF7L2) to interact with β-catenin and regulating its transcriptional activity, thereby inducing lipolysis and inhibiting lipogenesis; Zn-induced lipid degradation was mediated by histone deacetylase 3 (HDAC3) which was responsible for β-catenin deacetylation and the regulation of β-catenin signal under the Zn treatment. Mechanistically, Zn promoted lipid degradation via stimulating HDAC3-mediated deacetylation of β-catenin at lysine 311 (K311), which enhanced the interaction between β-catenin and TCF7L2 and then transcriptionally inhibited fatty acid synthase (FAS), 2-acylglycerol O-acyltransferase 2 (MOGAT2), and sterol regulatory element-binding protein 1 (SREBP1) expression, but elevated the mRNA abundance of adipose triglyceride lipase (ATGL), hormone-sensitive lipase a (HSLA) and carnitine palmitoyltransferase 1a1b (CPT1A1B). Overall, our research reveals a novel mechanism into the important roles of HDAC3/β-catenin pathway in Zn promoting lipolysis and inhibiting lipogenesis, and highlights the essential roles of K311 deacetylation in β-catenin actions and lipolytic metabolism, and accordingly provides novel insight into the prevention and treatment of steatosis in the vertebrates., Competing Interests: Declaration of competing interest All the authors declared no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Thermoelectric sulfide materials are of particular interest due to the earth-abundant and cost-effective nature of sulfur. Here, we report a new n-type degenerate semiconductor sulfide, AgBiPbS 3 , which adopts a Fm 3̅ m structure with a narrow band gap of ∼0.32 eV. Despite the homogeneous distribution of elements at the scale of micrometer, Ag 2 S nanoprecipitates with dimensions of several nanometers were detected throughout the matrix. AgBiPbS 3 exhibits a low room-temperature lattice thermal conductivity of 0.88 W m -1 K -1 , owing to the intrinsic low lattice thermal conductivity of Ag 2 S and the effective scattering of phonons at nanoprecipitate boundaries. Moreover, compared to AgBiS 2 , AgBiPbS 3 demonstrates a significantly improved weighted mobility of >16 cm 2 V -1 s -1 at 300 K, leading to an enhanced PF of 1.6 μW cm -1 K -2 at 300 K. The superior electrical transport in AgBiPbS 3 can be attributed to the high valley degeneracy of the L point (the conduction band minimum), which is contributed by the Pb s and Pb p orbitals. Further, Ga doping is found to be effective in modulating the Fermi levels of AgBiPbS 3 , leading to further enhancement of PF with a PF ave of 2.7 μW cm -1 K -2 in the temperature range of 300-823 K. Consequently, a relatively high ZT ave of 0.22 and a peak ZT of ∼0.4 at 823 K have been achieved in 3% Ga-doped AgBiPbS 3 , highlighting the potential of AgBiPbS 3 as an n-type thermoelectric sulfide.

Objective: We searched for a predictive biomarker that also predicts whether patients would benefit from immune checkpoint blockade (ICB) treatment from a few angles, because existing biomarkers no longer wholly replicate the interconnections of distinctive elements in the tumor microenvironment (TME)., Methods: We identified 55 pivotal IRGs by performing a WGCNA and univariate Cox regression analysis on a lung adenocarcinoma dataset from the TCGA database. The IRGPI model was then constructed using multivariate Cox regression analysis, which identified 16 genes and verified the use of the GSE68465 database. The AUC of the IRGPI was compared to those of the current biomarkers to determine its predictive potential. Then we examined the molecular and immunological properties of ICB and assessed its effectiveness using CTLA4 expression and TIDE., Results: Patients with a high IRGPI had a later clinical stage, more severe symptoms, and a worse prognosis. Patients with a low IRGPI had a higher immune escape potential and were less responsive to immunotherapy., Conclusion: The IRGPI may be a biomarker for determining the prognosis of patients and whether they respond favorably to ICB therapy., Competing Interests: None., (IJCEP Copyright © 2023.)

A novel Gram-stain-negative, facultatively anaerobic, and non-motile bacterial strain, designated SDUM287046 T , was isolated from the coastal sediments of Jingzi Port of Weihai, China. Cells of strain SDUM287046 T were rod-shaped with widths of 0.4-0.5 μm and lengths of 0.7-1.4 μm and could produce flexirubin-type pigments. Optimum growth of strain SDUM287046 T occurred at 33-35 °C, pH 7.0, and with 2% ( w / v ) NaCl. Oxidase activity was negative, but catalase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain SDUM287046 T was most closely related to Aequorivita aquimaris D-24 T (98.3%). The main cellular fatty acids were iso-C 15:0 , anteiso-C 15:0 , iso-C 17:0 3-OH, and summed feature 9 (comprised of iso-C 17:1 ω9c and/or C 16:0 10-methyl). The sole respiratory quinone was MK-6. The polar lipids consisted of phosphatidylethanolamine (PE), one aminolipid (AL), three unidentified glycolipids (GL), and three unidentified lipids (L). The DNA G + C content was 39.3 mol%. According to the integrated results of phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, we propose that strain SDUM287046 T represents a novel species of the genus Aequorivita , for which the name Aequorivita aurantiaca sp. nov. is proposed. The type strain is SDUM287046 T (=KCTC 92754 T = MCCC 1H01418 T ). Comparative genomic analysis showed that the 16 Aequorivita species shared 1453 core genes and differed mainly in amino acid metabolism, cofactor metabolism, and vitamin metabolism. Biogeographic distribution analysis indicated that the marine environments were the primary habitat of Aequorivita bacteria.

Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs. Mechanistically, WNT2 was positively regulated by its transcription factor SOX4, and in turn, SOX4 was upregulated by the canonical WNT2/FZD8/β-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSCs self-renewal and tumorigenicity. Furthermore, simultaneous overexpression of both WNT2 and SOX4 was correlated with poor survival and reduced responsiveness to chemotherapy in clinical GC specimens. Blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2-SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2-SOX4 positive feedback loop as a mechanism for GCSCs-induced chemo-drugs resistance and suggested that the WNT2-SOX4 axis may be a potential therapeutic target for gastric cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Primary meningeal melanoma is a rare type of melanocytic cancer originating from the melanocytes of the leptomeninges. It commonly presents as a solitary mass, and multifocal amelanotic lesions were scarcely reported. Diagnosis of multifocal melanoma is particularly challenging, clinically and diagnostically, especially in the absence of cutaneous nevi and melanin pigment. Surgical biopsy result is the gold standard. In this case study, we present an uncommon case of multifocal primary amelanotic meningeal melanomas mimicking lymphomas in the skull base and near the Sylvian fissure, which serves to provide reference value to the clinical diagnosis. Physicians should be aware of the existence of this special type in the clinical work.

Doping usually reduces lattice thermal conductivity because of enhanced phonon-impurity scattering. Here, we report unexpected doping effects on the lattice thermal conductivity of quasi-one-dimensional (quasi-1D) van der Waals (vdW) TiS 3 nanoribbons. As the nanoribbon thickness reduces from ~80 to ~19 nm, the concentration of oxygen atoms has a monotonic increase along with a 7.4-fold enhancement in the thermal conductivity at room temperature. Through material characterizations and atomistic modellings, we find oxygen atoms diffuse more readily into thinner nanoribbons and more sulfur atoms are substituted. The doped oxygen atoms induce significant lattice contraction and coupling strength enhancement along the molecular chain direction while have little effect on vdW interactions, different from that doping atoms induce potential and structural distortions along all three-dimensional directions in 3D materials. With the enhancement of coupling strength, Young's modulus is enhanced while phonon-impurity scattering strength is suppressed, significantly improving the phonon thermal transport., (© 2023. Springer Nature Limited.)

Introduction: Myelofibrosis is a rare disease. There is currently no published data reporting the demographics and outcome of myelofibrosis patients in Malaysia. We aimed to study the demographics, clinical characteristics, and outcome of our patients in Sarawak. Materials and methods : This non-interventional, retrospective, and multi-center study was conducted on secondary data of medical records collected at four Sarawak Public Hospitals. All adult myelofibrosis patients diagnosed between January 2001 and December 2021 were included. Results : A total of 63 patients (male 31) with myelofibrosis were included-47 (74.6%) primary and 16 (25.4%) secondary myelofibrosis. Eleven had antecedent polycythaemia vera, whereas five transformed from essential thrombocythaemia. The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.502. The median age was 59.0 years (33.0-93.0). Majority had high-risk (34/63(54.0%)) and intermediate-2 risk disease (19/63(30.2%)). JAK2V617F mutation was identified in 52 patients (82.5%), followed by CALR mutation in 6 (9.5%) and negative for both mutations in 5 (7.9%). Hydroxyurea was used as first-line therapy in 41/63 (65.1%), followed by interferon (8/63(12.7%)) and ruxolitinib (4/63(6.3%)). Out of 46 patients who received second-line therapy, 18 (39.1%) were switched to ruxolitinib and 9 (19.6%) to interferon. The median age of survival for overall patients was 6.8 years. The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to the no ruxolitinib arm, despite no statistical significance ( p  = 0.34). Patients who had good performance status had lower hazard of death than patients who had poor performance status (high-risk (95% confidence intervals): 0.06(0.013-0.239), p  < 0.001). Patients with intermediate risk disease had better overall survival compared to those in high-risk group (95% confidence intervals): 0.24(0.082-0.695), p  = 0.009). Conclusion : This registry provides a real-world overview of myelofibrosis patients in our state and highlights the key insight into the unmet clinical need., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The SaMy study was supported by Novartis Corporation via Research Collaboration. The authors declare that they have no conflict of interests., (© The Author(s) 2023.)

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.

Background: Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. It is important to note, however, that there are some differences between the diagnostic criteria used for NAFLD and MAFLD. Since the research on MAFLD is just beginning, however, evidence on its incidence and prevalence in the general population and in specific subpopulations remains limited., Aim: To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD. Exploring risk factors of MAFLD individuals., Methods: This was a retrospective, cross-sectional study. A total of 85242 adults were selected from the Chinese health management database in 2017-2022. The data of general information, laboratory indicators, lifestyle management and psychological status were obtained. MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions: Overweight/obesity, type 2 diabetes mellitus (T2DM) or metabolic dysregulation. Metabolic factors were not considered in NAFLD diagnosis standard. The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics. Continuous variables normally distributed were expressed as means ± SD. Categorical variables were expressed as frequencies and proportions. Binary logistic regression was used to determine risk factors of the MAFLD., Results: The prevalence of MAFLD and NAFLD was 40.5% and 31.0%, respectively. The MAFLD or NAFLD population is more likely to be older (M: 47.19 ± 10.82 vs 43.43 ± 11.96; N: 47.72 ± 11.17 vs 43.71 ± 11.66), male (M: 77.21% vs 44.43%; N: 67.90% vs 53.12%) and high body mass index (M: 26.79 ± 2.69 vs 22.44 ± 2.48; N: 26.29 ± 2.84 vs 23.29 ± 3.12) than the non-MAFLD or non-MAFLD population. In multivariate analysis, general information ( e.g. , ≥ 2 metabolic abnormalities OR = 3.38, (95%CI: 2.99-3.81), P < 0.001; diastolic blood pressure OR = 1.01, (95%CI: 1.00-1.01), P = 0.002), laboratory results [ e.g. ,total bilirubin (TBIL) OR = 0.98, (95%CI: 0.98-0.99), P < 0.001; serum uric acid(SUA) OR = 1.01, (95%CI: 1.01-1.01), P < 0.001], and lifestyle factors [ e.g. , drink beverage OR = 0.32, (95%CI: 0.17-0.63), P = 0.001] were influence factors for MAFLD. Our study results offer new insight into potential risk factors associated with fatty liver disease, including SUA, TBIL and creatinine, all of which are related to chronic renal disease (CKD)., Conclusion: MAFLD is more prevalent than NAFLD, with two-fifths of individuals meeting the diagnosis criteria. MAFLD and NAFLD populations have different clinical characteristics. CKD may be related with MAFLD., Competing Interests: Conflict-of-interest statement: The authors have no conflicts to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This research was conducted to investigate the effects of four dietary zinc (Zn) sources on growth performance, Zn metabolism, antioxidant capacity, endoplasmic reticulum (ER) stress, and tight junctions in the intestine of grass carp Ctenopharyngodon idella . Four Zn sources consisted of Zn dioxide nanoparticles (ZnO NPs), Zn sulfate heptahydrate (ZnSO 4 ·7H 2 O), Zn lactate (Zn-Lac), and Zn glycine chelate (Zn-Gly), respectively. Grass carp with an initial body weight of 3.54 g/fish were fed one of four experimental diets for 8 weeks. Compared to inorganic Zn (ZnSO 4 ·7H 2 O), grass carp fed the ZnO NPs and Zn-Gly diets exhibited better growth performance. Furthermore, grass carp fed the organic Zn (Zn-Lac and Zn-Gly) diets displayed enhanced Zn transport activity, improved intestinal histology, and increased intestinal tight junction-related genes expression compared to other groups. In comparison to other Zn sources, dietary ZnO NPs caused increased Zn deposition and damaged antioxidation capacity by suppressing antioxidant enzymatic activities and related gene expression in the intestine. Grass cap fed the ZnO NPs diet also exhibited lower mRNA abundance of endoplasmic reticulum (ER) stress- and tight junction-associated genes. According to the above findings, it can be concluded that dietary organic Zn addition (Zn-Lac and Zn-Gly) is more beneficial for intestinal health in grass carp compared to inorganic and nanoform Zn sources. These findings provide valuable insights into the application of organic Zn sources, specifically Zn-Lac and Zn-Gly, in the diets for grass carp and potentially for other fish species.

Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown. Here, we present evidence that lengsin, lens protein with glutamine synthetase domain (LGSN), a vital cell fate determinant, is overexpressed in GCSCs and is highly correlated with malignant progression and poor survival in GC patients. Ectopic overexpression of LGSN in GCSC-derived differentiated cells facilitated their dedifferentiation and treatment resistance by interacting with vimentin and inducing an epithelial-to-mesenchymal transition. Notably, genetic interference of LGSN effectively suppressed tumor formation by inhibiting GCSC stemness maintenance and provoking gasdermin-D-mediated pyroptosis through vimentin degradation/NLRP3 signaling. Depletion of LGSN combined with the chemo-drugs 5-fluorouracil and oxaliplatin could offer a unique and promising approach to synergistically rendering this deadly cancer eradicable in vivo. Our data place focus on the role of LGSN in GCSC regeneration and emphasize the critical importance of pyroptosis in battling GCSC., (© 2023. The Author(s).)

Excessive copper (Cu) intake leads to hepatic lipotoxicity disease, which has adverse effects on health, but the underlying mechanism is unclear. We found that Cu increased lipotoxicity by promoting Nrf2 recruitment to the ARE site in the promoters of five lipogenic genes (g6pd, 6pgd, me, icdh and pparγ). We also found that Cu affected the Nrf2 expression via different pathways: metal regulatory transcription factor 1 (MTF-1) mediated the Cu-induced Nrf2 transcriptional activation; Cu also enhanced the expression of Nrf2 by inhibiting the SP1 expression, which was achieved by inhibiting the negative regulator Fyn of Nrf2. These promoted the enrichment of Nrf2 in the nucleus and ultimately affected lipotoxicity. Thus, for the first time, we elucidated that Cu induced liver lipotoxicity disease by up-regulating Nrf2 expression via the MTF-1 activation and the inhibition of SP1/Fyn pathway. Our study elucidates the Cu-associated obesity and NAFLD for fish and possibly humans., 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 Elsevier B.V. All rights reserved.)