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Aims: Incidence of acute mountain sickness (AMS) ranges from 40%-90%, with high-altitude cerebral edema (HACE) representing a life-threatening end stage of severe AMS. However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated preventive effects on ischemia- or hypoxia-induced cardiovascular and cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism of HACE and the application of RIPC in preventing HACE onset., Methods: A hypobaric hypoxia chamber was used to simulate a high-altitude environment of 7000 meters. Metabolomics and metabolic flux analysis were employed to assay metabolite levels. Transcriptomics and quantitative real-time PCR (q-PCR) were used to investigate gene expression levels. Immunofluorescence staining was performed on neurons to label cellular proteins. The fluorescent probes Mito-Dendra2, iATPSnFR1.0, and CMTMRos were used to observe mitochondria, ATP, and membrane potential in cultured neurons, respectively. TUNEL staining was performed to detect and quantify apoptotic cell death. Hematoxylin and eosin (H&E) staining was utilized to analyze pathological changes, such as tissue swelling in cerebral cortex samples. The Rotarod test was performed to assess motor coordination and balance in rats. Oxygen-glucose deprivation (OGD) of cultured cells was employed as an in vitro model to simulate the hypoxia and hypoglycemia induced by RIPC in animal experiments., Results: We revealed a causative perturbation of glucose metabolism in the brain preceding cerebral edema. Ischemic preconditioning treatment significantly reprograms glucose metabolism, ameliorating cell apoptosis and hypoxia-induced energy deprivation. Notably, ischemic preconditioning improves mitochondrial membrane potential and ATP production through enhanced glucose-coupled mitochondrial metabolism. In vivo studies confirm that RIPC alleviates cerebral edema, reduces cell apoptosis induced by high-altitude hypoxia, and improves motor dysfunction resulting from cerebral edema., Conclusions: Our study elucidates the metabolic basis of HACE pathogenesis. This study provides a new strategy for preventing HACE that RIPC reduces brain edema through reprogramming metabolism, highlighting the potential of targeting metabolic reprogramming for neuroprotective interventions in neurological diseases caused by ischemia or hypoxia., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

High mobility group protein A2 (HMGA2) is widely recognized as a chromatin-binding protein, whose overexpression is observed in nearly all human cancers. It exerts its oncogenic effects by influencing various cellular processes such as the epithelial-mesenchymal transition, cell differentiation, and DNA damage repair. MicroRNA (miRNA) serves as a pivotal gene expression regulator, concurrently modulating multiple genes implicated in cancer progression, including HMGA2. It also serves as a significant biomarker for cancer. Circular RNA (circRNA) plays a crucial role in gene regulation primarily by sequestering miRNAs and impeding their ability to enhance the expression of other genes, including HMGA2. Increasingly, studies have underscored the vital role of miRNA/HMGA2 interactions in cancer. Given the significance of circRNA as an upstream regulatory mediator and the complexity of regulatory mechanisms, we hereby present a comprehensive overview of the pivotal role of circRNAs as upstream regulators of the miRNA//HMGA2 axis in human cancers. This insight may herald a novel direction for future cancer research., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Soil fungi participate in various ecosystem processes and are important factors driving the restoration of degraded forests. However, little is known about the changes in fungal diversity and potential functions under the development of different vegetation types during natural (secondary forest succession) and anthropogenic (reforestation) forest restoration. In this study, we selected typical forest succession sequences (including Pinus densiflora Siebold & Zucc., pine-broadleaf mixed forest of P. densiflora and Quercus acutissima Carruth., and Q. acutissima ), as well as natural secondary deciduous broadleaved mixed forests and planted forests of Robinia pseudoacacia on Kunyu Mountain for analysis. We used ITS rRNA gene sequencing to characterize fungal communities and used the FUNGuild database to predict fungal functional groups. The results showed that forest succession affected fungal β-diversity, but not the α-diversity. There was a significant increase in Basidiomycota and a decrease in Ascomycota in the later successional stage, accompanied by an increase in the functional groups of ectomycorrhizal fungi (ECM). Conversely, planted forests exhibited decreased fungal α-diversity and altered community compositions, characterized by fewer Basidiomycota and more Ascomycota and Mucoromycota. Planted forests led to a decrease in the relative abundances of ECM and an increase in animal pathogens. The TK content was the major factor explaining the distinction in fungal communities among the three successional stages, whereas pH, AP, and NH 4 + were the major factors explaining community variations between natural and planted forests. Changes in vegetation types significantly affected the diversity and functional groups of soil fungal communities during forest succession and reforestation, providing key insights for forest ecosystem management in temperate forests., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Phylogeographic studies have gained prominence in linking past geological events to the distribution patterns of biodiversity, primarily in mountainous regions. However, such studies often focus on plant taxa, neglecting the intricate biogeographical patterns of microbes, particularly soil microbial communities. This article explores the spatial distribution of the nematode-trapping fungus Arthrobotrys oligospora, a widespread microorganism, in a tectonically active region at the southeastern edge of the Qinghai-Tibetan Plateau. By analysing the genetic variation of this fungus alongside the historical structure of major river watersheds, we sought to uncover potential connections between the two. Our study involved sampling 149 strains from 116 sites across six major watersheds in the region., Results: The resulting haplotype network revealed five distinct clusters, each corresponding closely to a specific watershed. These clusters exhibited high haplotype diversity and low nucleotide diversity, supporting the notion of watershed-based segregation. Further analysis of haplotypes shared across watersheds provided evidence for three proposed past river connections. In particular, we found numerous shared haplotypes between the Yangtze and Mekong basins, as well as between the Yangtze and the Red basins. Evidence for a Irrawaddy-Salween-Red and a Yangtze-Pearl-Red river connections were also portrayed in our mapping exercise., Conclusions: These findings emphasize the crucial role of historical geomorphological events in shaping the biogeography of microbial biodiversity, alongside contemporary biotic and abiotic factors. Watershed perimeters emerged as effective predictors of such patterns, suggesting their suitability as analytical units for regional-scale studies. Our study also demonstrates the potential of microorganisms and phylogeographic approaches to complement traditional geological analyses, providing a more comprehensive understanding of past landscape structure and its evolution., (© 2024. The Author(s).)

Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng. But after oral administration, they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects. The sources of rare ginsenosides are extremely limited in P. notoginseng and other medical plants, which hinders their application in functional foods and drugs. Therefore, the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research. During 50 days at 25 ℃ and 150 rpm, A. fumigatus transformed PNS to 14 products (1-14). They were isolated by varied chromatographic methods, such as silica gel column chromatography, Rp-C 18 reversed phase column chromatography, semi-preparative HPLC, Sephadex LH-20 gel column chromatography, and elucidated on the basis of their 1 H-NMR, 13 C-NMR and ESIMS spectroscopic data. Then, the transformed products (1-14) were isolated and identified as Rk 3 , Rh 4 , 20 (R)-Rh 1 , 20 (S)-Protopanaxatriol, C-K, 20 (R)-Rg 3 , 20 (S)-Rg 3 , 20 (S)-Rg 2 , 20 (R)-R 2 , Rk 1 , Rg 5 , 20 (S)-R 2 , 20 (R)-Rg 2 , and 20 (S)-I , respectively. In addition, all transformed products (1-14) were tested for their antimicrobial activity. Among them, compounds 5 (C-K) and 7 [20 (S)-Rg 3 ] showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25, 1.25 μg/mL and 1.25, 25 μg/mL, respectively. This study lays the foundation for production of rare ginsenosides., (© 2024. The Author(s).)

Severe left ventricular outflow tract obstruction (LVOTO) of hypertrophic cardiomyopathy is an acutely life-threatening, must-not miss, cardiology emergency that infrequently presents to the emergency department (ED). Patients with this condition usually manifest chest pain, syncope, cardiogenic shock, and severe ischemia. LVOTO is easy misdiagnosed as acute coronary syndrome. In our patient, the ECG showed a significant ST-segment depression and a 0/0 mmHg blood pressure when the peak left ventricular outflow tract gradient was abruptly increased by provocable activities. However, the patient had normal coronaries on cardiac catheterization, and, upon being immediately treated with intravenous esmolol, his symptoms were relieved and blood pressure was normal after 30 minutes. This case highlights, not only that early and exact diagnosis of LVOTO is crucial, but also the importance of the therapeutic strategies used., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Despite improved treatments for acute myocardial infarction (AMI), myocardial fibrosis remains a key driver of adverse left ventricular (LV) remodeling and increased mortality. Fibroblast activation and proliferation significantly contribute to this process by enhancing cardiac fibrosis, which can lead to detrimental changes in LV structure. This study evaluates the effectiveness of 99m Tc-labeled fibroblast activation protein inhibitor ( 99m Tc-HFAPi) SPECT imaging in predicting LV remodeling over 12 months in post-AMI patients., Methods: A cohort of 58 AMI patients (46 males, median age 61 [53, 67] years) underwent baseline 99m Tc-HFAPi imaging (5 ± 2 days post-MI), perfusion imaging (6 ± 2 days post-MI), and echocardiography (2 ± 2 days post-MI). Additionally, 15 patients had follow-up 99m Tc-HFAPi and perfusion imaging, while 30 patients had follow-up echocardiography. Myocardial 99m Tc-HFAPi activity was assessed at the patient level. LV remodeling was defined as a ≥10% increase in LV end-diastolic diameter (LVEDD) or LV end-systolic diameter (LVESD) from baseline to follow-up echocardiography., Results: AMI patients displayed localized but non-uniform 99m Tc-HFAPi uptake, exceeding perfusion defects. Baseline 99m Tc-HFAPi activity exhibited significant correlations with BNPmax, LDHmax, cTNImax, and WBCmax, inversely correlating with LVEF. After 12 months, 11 patients (36.66%) experienced LV remodeling. Univariate regression analysis demonstrated an association between baseline 99m Tc-HFAPi uptake extent and LV remodeling (OR = 2.14, 95%CI, 1.04, 4.39, P = 0.038)., Conclusions: 99m Tc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Objectives: Mycobacterium abscessus is a non-tuberculous mycobacterial pathogen that causes pulmonary and skin infections globally. Clarithromycin plays a pivotal role in treating M. abscessus infections, with resistance often leading to treatment failure. While canonical mutations in the 23S rRNA residue 2270/2271 are recognized as the primary mechanism for acquired clarithromycin resistance, resistant isolates lacking these mutations have been widely reported. This study aims to identify new mechanisms of clarithromycin resistance in M. abscessus., Methods: We selected spontaneous resistant mutants derived from two parental strains characterized by erm(41) T28 and C28 sequevars, respectively. Whole-genome sequencing was performed on mutants lacking the 23S rRNA 2270/2271 mutations. Site-directed mutagenesis was used to confirm the resistance phenotypes of newly identified mutations. Bioinformatic analysis of publicly available genomes was conducted to evaluate the presence of these mutations in clinical isolates. The spatial localization of these mutations in the ribosome was analyzed to investigate potential mechanisms of resistance., Results: A total of 135 resistant mutants were selected from the parental strains. Sequencing of the 78 mutants lacking the 23S rRNA 2270/2271 mutations identified mutations within the peptidyl-transferase center and hairpin loops 35, 49, and 74 of the 23S rRNA. These noncanonical mutations were identified in 57 of 1875 genomes of clinical isolates. Thirteen representative mutations were introduced into the bacterial genome, and their contributions to macrolide resistance were confirmed. The newly identified mutations all localized at the entrance of the nascent peptide exit tunnel, potentially contributing to resistance by disrupting the macrolide binding pocket., Conclusion: Several noncanonical 23S rRNA mutations conferring clarithromycin resistance were identified. These mutations enhance our understanding of macrolide resistance in M. abscessus and could serve as important markers for diagnosing clarithromycin resistance., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: This study aimed to assess the association between drug-induced liver injury (DILI) and antibody-drug conjugates (ADCs) by comprehensively evaluating spontaneous reports submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004Q1 to 2022Q3., Research Design and Methods: All DILI cases with ADCs as primary suspected drugs were extracted from the FAERS database from 2004Q1 to 2022Q3 using OpenVigil 2.1. The reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and DILI risk were calculated., Results: A total of 504 DILI cases were attributed to ADCs during the study period. Patients with ADCs-related DILI ( n  = 504) had a mean age of 56.2 ± 18.4 years, with 167 cases not reporting patients' age. Females and males comprised 42.5% and 44.0% of the cases, respectively, while there was no information on gender in 13.5% of the cases. The DILI signals were detected in trastuzumab emtansine, enfortumab vedotin, brentuximab vedotin, polatuzumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan., Conclusions: The FAERS data mining suggested an association between DILI and some ADCs. Further studies are warranted to unraveling the underlying mechanisms and taking preventive measures for ADCs-related DILI.

Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H 2 O 2 ) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H 2 O 2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H 2 O 2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H 2 O 2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.

Cancer is one of the main reasons for death, and it threatens human life and health. Both the environment and genes can lead to cancers. It dates back more than a million years; more importantly, tumor cells can not be detected until they grow to a large number. Currently, cancers are treated with surgical excision or non-surgical procedures. By studying the interaction between ncRNAs and PKM2, we aim to provide new targets for diagnosis, treatment, and prognosis for cancers. Read relevant articles and made a summary and classification. Non-coding RNAs (ncRNAs) are RNAs that do not code for proteins. They perform a function in transcription and translation and can be used as targets for cancer therapy. Pyruvate kinase M2 (PKM2) is a form of PKM, and it catalyzes the glycolysis of the final cellular processes to promote tumorigenesis. Not only that, but it also plays non-metabolic functions, including the expression of the gene, cell proliferation, cell migration, and tumor angiogenesis in cancer cells. The existing studies have found that microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) can promote or inhibit the aerobic glycolysis of cancer cells by affecting PKM2, which increases or decrease the risk of cancers and affect the progression of cancers. This review focuses on the mechanism of ncRNAs regulating PKM2 in cancers and summarizes the roles of some ncRNAs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections., Clinical Trials: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525., Competing Interests: The authors declare no conflict of interest.

Background: Deep vein thrombosis (DVT) of the lower limbs is a venous reflux disorder caused by abnormal coagulation of blood components, primarily characterised by swelling and pain in the lower limbs. Key risk factors include prolonged immobility due to bed rest, pregnancy, postpartum or postoperative states, traumas, malignant tumours and long-term contraceptive use., Objective: To investigate the application of real-time shear wave elastography (SWE) in diagnosing lower-limb deep vein thrombosis (DVT)., Methods: A total of 91 patients with DVT were selected and divided into three groups: acute phase (n= 29), subacute phase (n= 30) and chronic phase (n= 32). The Young's modulus of the patients was measured using real-time SWE. The diagnostic efficacy of Young's modulus was evaluated by ROC curves. The hardness differences in Young's modulus across different parts of the same thrombus (head, body and tail) were measured using SWE., Results: Before treatment, significant differences were observed in Young's modulus among patients with DVT (P< 0.001). Following anticoagulant therapy, catheter-directed thrombolysis and systemic thrombolysis, significant differences were noted in Young's modulus among patients at the same stage but receiving different treatments (acute phase: P= 0.003; subacute phase: P= 0.014; chronic phase: P= 0.004). Catheter-directed thrombolysis had greater efficacy than anticoagulant therapy. The area under the curve for SWE in staging patients was 0.917, with a sensitivity of 92.36% and specificity of 93.81%. Significant differences in Young's modulus were found between the thrombus head and thrombus body and tail but not between the thrombus body and thrombus tail., Conclusion: Measurement of Young's modulus using SWE can serve as an auxiliary means of evaluating staging, predicting pulmonary embolism and selecting treatment in patients with DVT.

Background: Grapholita molesta is an important and harmful fruit pest worldwide, with widespread feeding hosts. Trypsin, an indispensable hydrolytic digestive protease in the insect gut, is crucial in digestion, growth and development. We analyzed the characteristics of the trypsin-encoding genes, screened for the optimal dose of RNAi mediated by nanocarriers, and investigated various indices of larval growth and development of G. molesta., Results: Gut content (GC) and RNase A degraded double-stranded RNA (dsRNA), with a faster degradation rate at higher concentrations. Star polycation (SPc) nanomaterials protected dsGFP from degradation by anion-cation binding and did not migrate through agarose gel. The key conserved motifs of the trypsin-encoding genes were similar, exhibiting high homology with those in other lepidopteran insects. An interference efficiency of ≈70% was achieved with SPc nanomaterial-mediated RNA interference with 0.05 μg dsRNA. The efficiency of continuous interference was stable. Trypsin activity, body weight of 8-day-old larvae, pupal weight and emergence rate were significantly reduced, and the larval stage was significantly prolonged., Conclusion: The investigated trypsin gene is a key target gene in the growth and development of G. molesta. We investigated the efficiency and convenience of feeding SPc nanomaterials in a functional study of insects. Our results provide valuable data for the development of efficient trypsin-targeting pesticides. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

2-Phenylethanol (2-PE) is a highly valuable aromatic alcohol utilized in fragrance, cosmetics and food industries. Due to the toxic by-products from chemical synthesis and the low productivity of the extraction method, bioproduction of 2-PE by yeast is considered promising. In this study, a wild-type Saccharomyces bayanus L1 strain producing 2-PE was isolated from soy sauce mash. Transcriptional analysis showed that 2-PE was synthesized via the Ehrlich pathway and Shikimate pathway in S. bayanus L1. By improving the fermentation conditions in shaking flasks, the maximum 2-PE titer reached 4.2 g/L with a productivity of 0.058 g/L/h within 72 h. In fed-batch fermentation, S. bayanus L1 strain produced 6.5 g/L of 2-PE within 60 h, achieving a productivity of 0.108 g/L/h. These findings suggest that S. bayanus L1 strain is an efficient 2-PE producer, paving the way for highly efficient 2-PE production., 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.)

Acute myeloid leukemia (AML) is a predominant form of leukemia. Central nervous system (CNS) involvement complicates its diagnosis due to limited diagnostic tools, as well as its treatment due to inadequate therapeutic methodologies and poor prognosis. Furthermore, its incidence rate is unclear. The mechanisms of AML cell mobilization from the bone marrow (BM) to the CNS are not fully elucidated, and the molecular factors contributing to CNS infiltration are insufficiently recognized. The present review aimed to enhance the understanding of CNS involvement of AML and its impact on CNS. The latest research on the pathways and mechanisms facilitating AML cells to escape the BM and infiltrate the CNS was reviewed. Additionally, novel therapeutic strategies targeting specific molecules and genes for treating CNS involvement in AML were examined.

Cancer development is thought to be closely related to aberrant epigenetic regulation, aberrant expression of specific non-coding RNAs (ncRNAs), and tumor microenvironment (TME). The m6A methylation is one of the most abundant RNA modifications found in eukaryotes, and it can determine the fate of RNA at the post-transcriptional level through a variety of mechanisms, which affects important biological processes in the organism. The m6A methylation modification is involved in RNA processing, regulation of RNA nuclear export or localisation, RNA degradation and RNA translation. This process affects the function of mRNAs and ncRNAs, thereby influencing the biological processes of cancer cells. TME accelerates and promotes cancer generation and progression during tumor development. The m6A methylation interacting with ncRNAs is closely linked to TME formation. Mutual regulation and interactions between m6A methylation and ncRNAs in TME create complex networks and mediate the progression of various cancers. In this review, we will focus on the interactions between m6A modifications and ncRNAs in TME, summarising the molecular mechanisms by which m6A interacts with ncRNAs to affect TME and their roles in the development of different cancers. This work will help to deepen our understanding of tumourigenesis and further explore new targets for cancer therapy., 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 origin and spread of agriculture facilitated a decline in human mobility and eventually led to a predominantly sedentary lifestyle globally, including on the Tibetan Plateau. Previous studies have proposed an evolution of prehistoric agriculture, from millet-based to barley-based farming. However, details regarding the process are vague. Here, we present diachronic changes in cropping structure from Xizang on the basis of a quantitative analysis of archaeobotanical remains from 12 sites located in southeastern Xizang. The advent of agriculture in Xizang began in the southeastern region around 4800 cal a BP and resulted in a quick spread of millet agriculture from the Hengduan Mountains to the Yarlung Zangbo River region. Subsequently, the introduction of barley and wheat in Xizang led to the transformation of millet-based farming into mixed farming after 3600 cal a BP. Eventually, around 3000 cal a BP, barley and wheat dominated across the entire Xizang with declining occurrences of millet. It took more than 600 years for barley and wheat to dominate in the Tibetan cropping system, which may reflect the time required for these exotic species to adapt physiologically to their new niche. In addition to the diachronic changes in crop farming, the ratio of barley to wheat and foxtail millet to broomcorn millet also varied at different elevations possibly due to local environmental variations and the crops' physiological requirements., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

As an important enterprises' practice in implementing the UN 2030 sustainable development, environmental, social, and governance (ESG) performance has drawn escalating attention from government, business and academia. This focus substantially impacts internationalization of enterprises. This paper tries to provide quantitative evidence of the impact of ESG performance of Chinese A-share listed companies on their international operation from 2009 to 2021. The results show that: (i) the ESG performance of listed enterprises exercise a significant positive impact on the internationalization operation. (ii) The effect of ESG performance on enterprises internationality is driven by increasing total factor productivity, enterprise reputation, and green innovation, as well as by mitigating financing constraint. (iii) Good ESG performance significantly boosts enterprise internationalization for non-heavy polluting, large-scale enterprises. This effect is also pronounced for enterprises with local government reports featuring a high frequency of environmental terms or those in high-tech industries., Competing Interests: 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., (© 2024 The Authors.)

Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the combination could be immunosuppressive. Lysosomes have previously been identified as a target for obinutuzumab cytotoxicity in CLL cells, but the mechanism remains unclear. In addition, studies have shown that lysosomotropic agents can cause synergistic cell death in vitro when combined with the BTK inhibitor, ibrutinib, in primary CLL cells. This indicates that targeting lysosomes could be a treatment strategy for CLL. In this study, we have shown that obinutuzumab induces lysosome membrane permeabilization (LMP) and cathepsin D release in CLL cells. Inhibition of cathepsins reduced obinutuzumab-induced cell death in CLL cells. We further determined that the lysosomotropic agent siramesine in combination with venetoclax increased cell death in primary CLL cells through an increase in reactive oxygen species (ROS) and cathepsin release. Siramesine treatment also induced synergistic cytotoxicity when combined with venetoclax. Microenvironmental factors IL4 and CD40L or incubation with HS-5 stromal cells failed to significantly protect CLL cells from siramesine- and venetoclax-induced apoptosis. We also found that siramesine treatment inhibited autophagy through reduced autolysosomes. Finally, the autophagy inhibitor chloroquine failed to further increase siramesine-induced cell death. Taken together, lysosome-targeting drugs could be an effective strategy in combination with venetoclax to overcome drug resistance in CLL.

Mitochondrial carrier homolog 2 (MTCH2) is a member of the solute carrier 25 family, located on the outer mitochondrial membrane. MTCH2 was first identified in 2000. The development in MTCH2 research is rapidly increasing. The most well-known role of MTCH2 is linking to the pro-apoptosis BID to facilitate mitochondrial apoptosis. Genetic variants in MTCH2 have been investigated for their association with metabolic and neurodegenerative diseases, however, no intervention or therapeutic suggestions were provided. Recent studies revealed the physiological and pathological function of MTCH2 in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction via regulating mitochondrial apoptosis, metabolic shift between glycolysis and oxidative phosphorylation, mitochondrial fusion/fission, epithelial-mesenchymal transition, etc. This review endeavors to assess a total of 131 published articles to summarise the structure and physiological/pathological role of MTCH2, which has not previously been conducted. This review concludes that MTCH2 plays a crucial role in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction, and the predominant molecular mechanism is regulation of mitochondrial function. This review gives a comprehensive state of current knowledgement on MTCH2, which will promote the therapeutic research of MTCH2., Competing Interests: All the authors declare that they do not have any financial and personal relationships with other people or organizations that could influence the design, supervision or reporting of their work. The authors declare that they have no competing interests., (© 2024 Peng et al.)

Non-coding RNAs are mainly divided into two categories, one is small non-coding RNA represented by miRNA, and the other is long non-coding RNA longer than 200 bp. Further studies on non-coding RNAs have revealed that long non-coding RNAs not only have carcinogenic effects, but also have potential links with miRNAs. Antisense non-coding RNA in the INK4 locus (ANRIL/CDKN2B-AS1), one of the five subtypes of long non-coding RNA, has been proved to play a role of oncogene in many cancers, such as gastric cancer, cervical cancer, prostate cancer and non-small cell lung cancer. Knockdown ANRIL can significantly inhibit the proliferation and migration of cancer cells, while also negatively regulating the expression of related miRNAs. This suggests that ANRIL may serve as a potential target for the development of drugs that provide new strategies to improve the effectiveness of cancer treatment. In our review, we summarize the current association between ANRIL and miRNAs in various cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens., Methods: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG)., Results: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events., Conclusions: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes., Trial Registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 )., (© 2024. The Author(s).)

Background and Objective: High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center., Methods: We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups., Results: There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups., Conclusions: In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

A sensitive photoelectrochemical (PEC) biosensor for silver ions (Ag + ) was developed based on Zn-Co doped C and CdS quantum dot (CdS QD) nanomaterials. Hydrophobic modified sodium alginate (HMA), which could stabilize and improve the PEC performance of CdS QDs, was also used for the construction of PEC sensors. Especially, Zn-Co doped C, CdS QDs and HMA were sequentially modified onto an electrode surface via the drop-coating method, and a C base rich DNA strand was then immobilized onto the modified electrode. As the C base in DNA specifically recognized Ag + , it formed a C-Ag + -C complex in the presence of Ag + , which created a spatial steric hindrance, resulting in a reduced PEC response. The sensing platform is sensitive to Ag + in the range of 10.0 fM to 0.10 μM, with a limit of detection of 3.99 fM. This work offers an ideal platform to determine trace heavy metal ions in environmental monitoring and bioanalysis.

As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Among all cancers in the world, the incidence rate of digestive system neoplasms accounts for about 25%, while the mortality rate accounts for about 35%. Difficulty in detecting early digestive system cancers and its poor prognosis are the two main reasons for the high mortality rate. Understanding of the basic cellular processes is of significance and autophagy is one of these processes. Considering the importance of autophagy in pathological state functions, the mechanism of autophagy was initially carried out. In this paper, we will review the molecular mechanisms and biological functions of autophagy-associated ncRNAs in different types of digestive system cancers. Autophagy is a process that supports nutrient cycling and metabolic adaptation accomplished through multi-step lysosomal degradation. It has been suggested that autophagy has a dual role in cancer, which limits tumorigenesis in some stages but promotes tumor progression in others. NcRNAs are also shown to modulate cellular autophagy and thus affect the development of digestive system neoplasms. More and more evidence suggests that the regulation of autophagy by ncRNAs plays a complex role in cancer initiation, progression, metastasis, recurrence, and treatment resistance, which might make ncRNAs therapeutic targets for digestive system neoplasms. While miRNAs participate mainly in post-transcriptional regulation, lncRNAs, and circRNAs usually serve as molecular sponges that have more diverse regulatory functions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Despite advanced clinical treatment, the mortality rate of cancer patients is high. Recent studies have linked the development of cancer to inflammation. Many cancers are exacerbated by the emergence of inflammatory responses, and non-coding RNAs play an important role in inflammation. Non-coding RNAs include microRNAs, circular RNAs, long-chain noncoding RNAs, etc. The non-coding RNA regulatory network composed of microRNAs, circular RNAs and long-chain non-coding RNAs is involved in the regulatory process of multiple gene expression. They can act on various signaling pathways, such as wnt/β-catenin, nuclear factorkappa B, phosphatidylinositol 3 kinase/ AKT, mitogen-activated protein kinase, and so on. These signaling pathways can control the occurrence of inflammatory response to some extent, such as regulating the expression of inflammatory cytokines (such as interleukin-6, interferongamma, tumor necrosis factor-α, and so on), making them upregulated or down-regulated. Therefore, it is important to study the role of non-coding RNAs in inflammation to contribute to the future of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cell migration, a hallmark of cancer malignancy, plays a critical role in cancers. Improperly initiated or misdirected cell migration can lead to invasive metastatic cancer. Migrasomes are newly discovered vesicular cellular organelles produced by migrating cells and depending on cell migration. Four marker proteins [NDST1 (bifunctionalheparan sulfate N-deacetylase/N-sulfotransferase 1), EOGT (Epidermal growth factor domains pecific O-linked N-acetylglucosaminetransferase), CPQ (carboxypeptidase Q), and PIGK (phosphatidylinositol glycan anchor biosynthesis, class K)] of migrasomes were successfully identified. There are three marker proteins (NDST1, PIGK, and EOGT) of migrasome expressed in cancer. In this review, we will discuss the process of migrasome discovery, the formation of migrasome, the possible functions of migrasome, and the differences between migrasomes and exosomes, especially, the biological functions of migrasome marker proteins in cancer, and discuss some possible roles of migrasomes in cancer. We speculate that migrasomes and migracytosis can play key roles in regulating the development of cancer., (© 2024. The Author(s).)

Three-dimensional (3D) cell culture has been used in many fields of biology because of its unique advantages. As a representative of the 3D systems, 3D spheroids are used as building blocks for tissue construction. Larger tumor aggregates can be assembled by manipulating or stacking the tumor spheroids. The motivation of this study is to investigate the behavior of the cells distributed at different locations of the spheroids in the fusion process and the mechanism behind it. To this aim, spheroids with varying grades of maturity or age were generated for fusion to assemble micro-tumor tissues. The dynamics of the fusion process, the motility of the cells distributed in different heterogeneous architecture sites, and their reactive oxygen species profiles were studied. We found that the larger the spheroid necrotic core, the slower the fusion rate of the spheroid. The cells that move were mainly distributed on the spheroid's surface during fusion. In addition to dense microfilament distribution and low microtubule content, the reactive oxygen content was high in the fusion site, while the non-fusion site was the opposite. Last, multi-spheroids with different maturities were fused to complex micro-tissues to mimic solid tumors and evaluate Doxorubicin's anti-tumor efficacy., (© 2024 IOP Publishing Ltd.)

Background: Anemia is a significant contributor to the global disease burden, of which thalassemia is the most common hereditary anaemic disease. Previous estimates were based on data that were geographically limited and lacked comprehensive global analysis. This study provides the prevalence, incidence, mortality and disability-adjusted life years (DALYs) of thalassemia in 204 countries and regions of thalassemia between 1990 and 2021, focusing on the age structure and time trends of the disease burden. To provide effective information for health policy, allocation of medical resources and optimization of patient management programs., Methods: Using the standardised Global Burden of Disease (GBD) methodologies, we aimed to derive a more precise representation of the health burden posed by thalassemia by considering four distinct types of epidemiological data, namely the incidence at birth, prevalence, mortality and DALYs. The presented data were meticulously estimated and displayed both as numerical counts and as age-standardised rates per 100,000 persons of the population, accompanied by uncertainty interval (UI) to highlight potential statistical variability. The temporal trends spanning the years 1990-2021 were subjected to a rigorous examination utilizing Joinpoint regression analysis. This methodological approach facilitated the computation of the annual percentage change (APC) and the average annual percentage change (AAPC), along with their corresponding 95% confidence intervals (CIs)., Findings: Globally, the age-standardized prevalence rates (ASPR), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates for thalassemia in 2021 were 18.28 per 100,000 persons (95% UI 15.29-22.02), 1.93 per 100,000 persons (95% UI 1.51-2.49), 0.15 per 100,000 persons(95% UI 0.11-0.20), and 11.65 per 100,000 persons (95% UI 8.24-14.94), respectively. Compared to 1990, these rates have decreased by 0.18 (95% UI -0.22 to -0.14), 0.25 (95% UI -0.30 to -0.19), 0.48 (95% UI -0.60 to -0.28), and 0.49 (95% UI -0.62 to -0.29) respectively. In 2021, the ASIR of thalassemia was highest in East Asia at 7.35 per 100,000 persons (95% UI 5.37-10.04), and ASMR was highest in Southeast Asia at 0.37 per 100,000 persons (95% UI 0.29-0.45).Gender comparisons showed negligible differences in disease burden, with the highest prevalence noted in children under five, decreasing with age. The global ASPR and ASMR declined from 1990 to 2021 overall, though an increasing trend in prevalence was found among the elderly. Joinpoint analysis revealed that the global ASPR increased between 2018 and 2021 (APC = 9.2%, 95% CI: 4.8%-13.8%, P < 0.001), ASIR decreased (APC = -7.68%, 95% CI: -10.88% to -4.36%, P < 0.001), and there was a significant rise in ASMR from 2019 to 2021 (APC = 4.8%, 95% CI: 0.1%-9.6%, P < 0.05). Trends in ASPR and ASMR varied across regions, with notable changes in South Asia., Interpretation: The global burden of thalassemia, reflected in its prevalence, incidence, mortality, and DALYs, exhibits significant disparities. Geographic and demographic shifts in disease distribution have been observed from 1990 to 2021, with an overall decrease in burden, yet an increase in cases among the elderly population. Analysis of epidemiological trends over time highlights the influence of health policies and significant public health interventions on thalassemia outcomes. There data are crucial for healthcare professionals, policymakers, and researchers to refine and enhance management strategies, aiming to further mitigate thalassemia's global impact., Funding: National Natural Science Foundation of China; Guizhou Province Science and Technology Project; Guizhou Province Science and Technology Foundation of Health Commission., Competing Interests: All authors hereby attest that they do not have any conflicts of interest related to this article., (© 2024 The Author(s).)

Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular γ-aminobutyric acid (GABA) transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.

Breast cancer (BC) ranks first among female malignant tumors and involves hormonal changes and genetic as well as environmental risk factors. In recent years, with the improvement of medical treatment, a variety of therapeutic approaches for breast cancer have emerged and have strengthened to accommodate molecular diversity. However, the primary way to improve the effective treatment of breast cancer patients is to overcome treatment resistance. Recent studies have provided insights into the mechanisms of resistance to exosome effects in BC. Exosomes are membrane-bound vesicles secreted by both healthy and malignant cells that facilitate intercellular communication. Specifically, exosomes released by tumor cells transport their contents to recipient cells, altering their properties and promoting oncogenic components, ultimately resulting in drug resistance. As important coordinators, non-coding RNAs (ncRNAs) are involved in this process and are aberrantly expressed in various human cancers. Exosome-derived ncRNAs, including microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as crucial components in understanding drug resistance in breast cancer. This review provides insights into the mechanism of exosome-derived ncRNAs in breast cancer drug resistance, thereby suggesting new strategies for the treatment of BC., (© 2024. The Author(s).)

An ultralight 3D carbon fiber aerogel with good flexibility is developed via soaking cotton in water and then calcinating at a high temperature. This cotton-derived carbon material is constituted by amorphous carbon and retains slight oxygen-containing groups. Besides, a lot of hollow carbon nanocapsules are yielded on the inside surface, resulting in abundant micropores and mesopores. Systemic investigations explore the molecular transformation from cotton to carbon fiber, and the formation of carbon nanocapsules. In the adsorption process for methyl orange (MO), this carbon fiber aerogel exhibits both a rapid adsorption rate and the ultrahigh adsorbability of 862.9 mg/g, outclassing most of carbon materials reported. Therefore, a dynamic sewage treatment system is built and consecutively removes hydrosoluble pollution for a long-term running time. For the cotton-derived carbon fiber aerogel, the good mechanical flexibility, excellent adsorption property, and high stability jointly provide a vast application prospect in future industrial wastewater remediation., 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.)

Background: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension., Methods: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected., Results: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001)., Conclusion: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension.., 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 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), autoimmune inflammatory diseases of the central nervous system, affect the optic nerve and brain. A lumbar puncture to obtain biomarkers is highly invasive. Serum biomarkers and optical coherence tomography angiography (OCTA) are more accessible and less expensive than magnetic resonance imaging and provide reliable, reproducible measures of neuroaxonal damage. This study investigated the association between serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and OCTA metrics. Serum sNfL and sGFAP levels, OCTA values, and clinical characteristics were compared among 91 patients with NMOSD, 81 patients with MS, and 34 healthy controls (HCs) at baseline and 1-year follow-up., Results: sNfL and sGFAP levels were higher while the sGFAP/sNfL quotients were significantly lower in NMOSD and MS patients than those in HCs. At baseline, the average thicknesses of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGC-IPL) were significantly smaller in NMOSD and MS patients than those in HCs (pRNFL: MS 92.0 [80.2; 101] μm, NMOSD 80.0 [59.0; 95.8] μm, vs HC 99.0 [92.0; 104] μm, p < 0.001; mGC-IPL: MS 74.5 [64.2; 81.0] μm, NMOSD 68.0 [56.0; 81.0] μm, vs HC 83.5 [78.0; 88.0] μm, p < 0.001). The vessel density (VD) and perfusion density (PD) were increased in MS patients without optic neuritis compared to HCs (VD: MS 16.7 [15.6; 17.9] HC 15.3 [13.4; 16.9], p = 0.008; PD: MS 0.41 [0.38; 0.43], HC 0.37 [0.32; 0.41], p = 0.017). In NMOSD patients without optic neuritis, sNfL was significantly associated with PD at baseline (r = 0.329, q = 0.041). The baseline and follow-up values of the sNfL level and average pRNFL and mGC-IPL thicknesses in MS patients showed significant differences. NMOSD patients showed significant differences between baseline and follow-up sNfL and sGFAP levels but not OCTA metrics., Conclusion: Changes in retinal microvasculature might occur earlier than those in retinal structure and may therefore serve as a promising diagnostic marker for early NMOSD. The combination of serum markers and OCTA metrics could be used to evaluate and differentiate between MS and NMOSD., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This research aimed to explore the involvement of interleukins (IL) - IL-6, IL-17, IL-21, and IL-23 - in the evolution and diagnosis of non-alcoholic liver fibrosis and cirrhosis., Methods: The study subjects were selected from the patients who visited the Department of Hepatology of X Hospital in Y City from August 2021 to April 2023. Peripheral blood samples were collected. All participants were divided into liver fibrosis, cirrhosis, hepatitis, and healthy subjects four groups. IL-21, IL-17, IL23, IL-6 were detected by double antibody sandwich., Results: The results showed that there was a significant difference in the levels of IL-17, IL-21, and IL-23 among the 4 groups (P<0.0001). ROC curve analysis showed that the AUC values of IL-17, IL-21 and liver fiber 4 items were >0.70, suggesting that the diagnostic efficacy of IL-17, IL-21 was similar to that of liver fiber 4 items. Spearman correlation analysis showed that IL-17 had a positive correlation with collagen type III N-peptide, type IV collagen, and Laminin (P < 0.05), and no correlation with Hyaluronic acid (P > 0.05)., Conclusion: IL-17, IL-21, and IL-23 play a pivotal role in the inflammatory pathways associated with liver injuries, establishing themselves as potent auxiliary diagnostic markers in identifying liver fibrosis and cirrhosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang et al.)

In recent years, tumor immunotherapy, aimed at increasing the activity of immune cells and reducing immunosuppressive effects, has attracted wide attention. Among them, immune checkpoint blocking (ICB) is the most commonly explored therapeutic approach. All approved immune checkpoint inhibitors (ICIs) are clinically effective monoclonal antibodies (mAbs). Compared with biological agents, small-molecule drugs have many unique advantages in tumor immunotherapy. Therefore, they also play an important role. Immunosuppressive signals such as PD-L1, IDO1, and TGF-β, etc. overexpressed in tumor cells form the tumor immunosuppressive microenvironment. In addition, the efficacy of multi-pathway combined immunotherapy has also been reported and verified. Here, we mainly reviewed the mechanism of tumor immunotherapy, analyzed the research status of small-molecule modulators, and discussed drug candidates' structure-activity relationship (SAR). It provides more opportunities for further research to design more immune small-molecule modulators with novel structures., 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 Inc. All rights reserved.)

Aims: To investigate the trajectory, influencing factors and dynamic relationships between fear of cancer recurrence (FCR) and quality of life (QOL) in lung cancer patients., Design: Prospective longitudinal study., Methods: Longitudinal data from 310 lung cancer patients across three hospitals in China were assessed at 1, 3, 6 and 12 months postoperatively (T 1 -T 4 ). Descriptive statistics characterised patient demographics, clinical characteristics, levels of FCR and QOL. A linear mixed-effects model was employed to analyse FCR trajectories, identify influencing factors on these trajectories, and predict the impact of FCR on QOL., Results: FCR changed significantly over time, with a slight decrease during T 1 -T 2 , an increase at T 3 and gradual decline at T 4 . Higher fear levels were associated with female sex, suburban or rural residency, being a family breadwinner, presence of comorbidities and negative coping behaviours, and low family resilience. QOL negatively correlated with FCR, and FCR predicted lower QOL., Conclusions: At 3 and 6 months postoperatively, lung cancer patients, especially women, suburban or rural residents, family breadwinners, those with comorbidities, negative coping behaviours and low family resilience, reported high levels of FCR. Healthcare providers should pay special attention to lung cancer patients especially during the period of 3-6 months post-surgery and offer tailored interventions to improve their QOL., Implications for the Profession and Patient Care: Understanding the FCR trajectories, its influencing factors and its negative impacts on QOL can guide the development of targeted interventions to reduce fear and enhance well-being in patients with cancer., Impact: Identifying the trajectories and influencing factors of fear of lung cancer recurrence in patients at different time points informs future research on targeted interventions to improve QOL., Reporting Method: The study adhered to the guidelines outlined in the Statement on Reporting Observational Longitudinal Research., (© 2023 John Wiley & Sons Ltd.)

Introduction: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes., Methods: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index., Results: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks., Conclusions: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

HPV vaccines are highly effective in preventing HPV-associated cancers; however, HPV vaccination uptake is low among Chinese students studying at U.S. colleges. The purposes of this study were to evaluate (a) perceived barriers and influential others trusted for advice regarding HPV vaccination and (b) factors (i.e. HPV vaccination, acculturation) related to barriers and influential advisors among 18- to 26-year-old Chinese students attending U.S. colleges. We used a cross-sectional design to obtain self-reported data in 2019 from a chain-referral sample of 213 Chinese students. Among 125 respondents who were unvaccinated or partially vaccinated, the reported barriers to receiving the HPV vaccine included: (a) lack of recommendations from a healthcare provider, (b) lack of risk perception for HPV infection, and (c) limited knowledge about HPV vaccination locations. The influential advisors for receiving HPV vaccination were doctors, parents, self, nurses, and same-sex friends. Multivariate analysis revealed that unvaccinated respondents were more likely to report the following barriers to HPV vaccination: (a) lack of recommendations from a healthcare provider, (b) lack of risk perception for HPV infection, (c) limited knowledge about vaccination locations, and (d) uncertainty about effectiveness. High Asian identified respondents were more likely to perceive barriers related to limited knowledge about vaccination locations and uncertainty about effectiveness, while they were less likely to state nurses as influential advisors. Individuals who received one or more HPV vaccine doses were more inclined to view same-sex friends and nurses as influential advisors for HPV vaccination. The influence of culture on preferences for information sources, such as specific providers and provider gender, needs to be addressed. Programs designed to decrease barriers and improve HPV vaccination among Chinese students should also focus on acculturation status.

Background: Fear of cancer recurrence (FCR) significantly impacts the treatment and prognosis of lung cancer survivors. However, the mechanisms and factors contributing to FCR and its related consequences in lung cancer remain poorly understood., Objective: To evaluate the validity of the Lee-Jones Theoretical Model of FCR in lung cancer survivors., Methods: A cross-sectional survey was conducted among 257 lung cancer survivors who had undergone surgical treatment 1 year prior. The participants completed a comprehensive set of questionnaires, and the data were analyzed using structural equation modeling to test the proposed model., Results: The analysis confirmed direct relationships between family resilience, coping behaviors, illness perceptions, FCR triggers, and FCR. Fear of cancer recurrence was also found to have a direct negative impact on quality of life (QOL). Furthermore, levels of family resilience, coping behaviors, illness perceptions, and FCR triggers indirectly influenced QOL through their association with FCR., Conclusions: This study provides partial support for the validity of the Lee-Jones Theoretical Model of FCR in lung cancer survivors. The findings contribute to a better understanding of FCR in this population and lay the groundwork for targeted interventions. Effective strategies to reduce FCR in lung cancer survivors should focus on enhancing family resilience, improving disease cognition, minimizing FCR triggers, and guiding patients toward adopting positive coping styles, ultimately improving their QOL., Implications for Practice: Fear of cancer recurrence plays a vital role in relationships between internal and external cues and QOL. We can construct interventions to enhance the QOL of survivors based on the FCR influencing factors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu 2+ ) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu 2+ was reduced to Cu + by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H 2 O 2 ) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it's noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Family resilience helps cancer-affected families overcome challenges and may influence an individual's fear of cancer recurrence (FCR). Identifying distinct classes of family resilience among lung cancer patients is crucial for tailored interventions. This study aimed to identify latent classes of family resilience in lung cancer patients and explore their relationships with FCR., Methods: Three hundred ten lung cancer patients from three hospitals in Fujian were recruited from June to September 2021. Clinical data were extracted from medical records, while sociodemographic details, family resilience, and FCR were self-reported. A latent class analysis was performed to identify family resilience classes., Results: A 4-class solution showed the best fit. Compared to Class 1, the patients who had no comorbidities (ORs = 3.480-16.005) had an increased likelihood of belonging to Class 2 and 3, while those who were not family breadwinners (ORs = 0.118-0.176) had a decreased likelihood. Further, the patients who (1) did not lack interest/pleasure in doing things during the past 2-week period (OR = 7.057), (2) were never smokers (OR = 6.230), and (3) were urban residents (OR = 8.985) had an increased likelihood of belonging to Class 4, while those who were (1) male (OR = 0.167), (2) not the family breadwinner (OR = 0.152), and (3) had none or only one child (OR = 0.203) had a decreased likelihood of belonging to Class 4. The FCR level differed significantly among these four classes., Conclusion: Our study identified four distinct classes of family resilience among Chinese lung cancer patients. FCR severity decreased with increasing levels of family resilience., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As an important characteristic of tumor, acidic tumor microenvironment (TME) is closely related to immune escape, invasion, migration and drug resistance of tumor. The acidity of the TME mainly comes from the acidic products produced by the high level of tumor metabolism, such as lactic acid and carbon dioxide. pH regulators such as monocarboxylate transporters (MCTs), carbonic anhydrase IX (CA IX), and Na + /H + exchange 1 (NHE1) expel protons directly or indirectly from the tumor to maintain the pH balance of tumor cells and create an acidic TME. We review the functions of several pH regulators involved in the construction of acidic TME, the structure and structure-activity relationship of pH regulator inhibitors, and provide strategies for the development of small-molecule antitumor inhibitors based on these targets., 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 Masson SAS. All rights reserved.)

Metabolism is reprogrammed in a variety of cancer cells to ensure their rapid proliferation. Cancer cells prefer to utilize glycolysis to produce energy as well as to provide large amounts of precursors for their division. In this process, cancer cells inhibit the activity of pyruvate dehydrogenase complex (PDC) by upregulating the expression of pyruvate dehydrogenase kinases (PDKs). Inhibiting the activity of PDKs in cancer cells can effectively block this metabolic transition in cancer cells, while also activating mitochondrial oxidative metabolism and promoting apoptosis of cancer cells. To this day, the study of PDKs inhibitors has become one of the research hotspots in the field of medicinal chemistry. Novel structures targeting PDKs are constantly being discovered, and some inhibitors have entered the clinical research stage. Here, we reviewed the research progress of PDKs inhibitors in recent years and classified them according to the PDKs binding sites they acted on, aiming to summarize the structural characteristics of inhibitors acting on different binding sites and explore their clinical application value. Finally, the shortcomings of some PDKs inhibitors and the further development direction of PDKs inhibitors are discussed., 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 Inc. All rights reserved.)

Accurate detection of fibrotic interstitial lung disease (f-ILD) is conducive to early intervention. Our aim was to develop a lung graph-based machine learning model to identify f-ILD. A total of 417 HRCTs from 279 patients with confirmed ILD (156 f-ILD and 123 non-f-ILD) were included in this study. A lung graph-based machine learning model based on HRCT was developed for aiding clinician to diagnose f-ILD. In this approach, local radiomics features were extracted from an automatically generated geometric atlas of the lung and used to build a series of specific lung graph models. Encoding these lung graphs, a lung descriptor was gained and became as a characterization of global radiomics feature distribution to diagnose f-ILD. The Weighted Ensemble model showed the best predictive performance in cross-validation. The classification accuracy of the model was significantly higher than that of the three radiologists at both the CT sequence level and the patient level. At the patient level, the diagnostic accuracy of the model versus radiologists A, B, and C was 0.986 (95% CI 0.959 to 1.000), 0.918 (95% CI 0.849 to 0.973), 0.822 (95% CI 0.726 to 0.904), and 0.904 (95% CI 0.836 to 0.973), respectively. There was a statistically significant difference in AUC values between the model and 3 physicians (p < 0.05). The lung graph-based machine learning model could identify f-ILD, and the diagnostic performance exceeded radiologists which could aid clinicians to assess ILD objectively., (© 2024. The Author(s).)