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The Masculinizer (Masc) gene plays a crucial role in masculinization during insect embryonic gonadal development. Nevertheless, the Masc expression pattern and function in crabs remain largely unknown. In the present study, we screened and validated the Masc gene from transcriptome data of mud crab S. paramamosain. The Masc relative transcript level in the testis was significantly higher than that of ovaries and other tissues, as measured by quantitative real-time PCR. In situ hybridization showed that Masc exhibited a significant signal throughout all stages of testicular development. The phylogenetic analysis revealed conservation in the evolution of crustaceans, potentially indicating its functional importance. Masc RNA interference showed that the expression of testis bias-related genes decreased significantly while the ovary bias-related genes increased significantly. Transcriptome data suggested that Masc regulates several signaling pathways, including the mTOR, Wnt, insulin, and other sex-related pathways. These results indicate that Masc may play a role in mud crab male development with possible application in sex control in aquaculture., 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.)

Electrochemical biosensors hold great promise for the rapid screening of viral infectious diseases. However, the recognition elements of these biosensors are typically limited to antibodies, aptamers, and molecularly imprinted polymers. In this study, acetylated sialic acids were explored as recognition elements because they serve as natural viral receptors expressed on host cells. Specifically, 4-O-acetylated-SA (4-O-Ac-SA) and 9-O-Ac-SA, were synthesized selectively, and their binding affinity with the SARS-CoV-2 S antigen was examined. The S antigen tended to bind to 9-O-Ac-SA. Additionally, the biocompatibility and neutralizing effects of 4/9-O-Ac-SA on the S antigen were validated. The validation demonstrated that 9-O-Ac-SA could efficiently inhibit S antigen binding to host cells. The cluster glycoside effect of the recognition between the S antigen and 9-O-Ac-SA was validated. Subsequently, an electrochemical biosensor for the rapid screening of viral antigens was developed using 9-O-Ac-SA as the recognition element. The application of electrochemical impedance spectroscopy as a readout method allowed for the identification of the S antigen at concentrations of 10 ng/mL with acceptable stability and repeatability. The biosensor demonstrated a strong linear response over the range of 10∼1 × 10 4  ng/mL. In summary, the study presented a promising recognition element for the development of electrochemical biosensors for rapid viral infection screening. The utilization of glycans for viral antigen detection could pave the way for innovative advances in electrochemical biosensor technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To determine the optimal treatment modality for intracranial germinoma (IG)., Materials and Methods: A search of Medline, Embase, Web of Science and Cochrane Library was conducted up to April, 2024. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated. Subgroup analysis was applied according to radiotherapy (RT) alone or with chemotherapy (CTx)., Results: Total 37 studies were included in systematic review. Most IG patients were treated with biopsy or resection followed by RT with or without CTx. Prognosis of IG patients with different surgical resection is similar. Meta-analyses demonstrated focal field RT were with higher recurrence rate compared with craniospinal irradiation (CSI) [RR = 7.128, 95% CI (5.083, 9.995)], whole-brain RT (WBRT) [RR = 4.094, 95% CI (2.923, 5.735)] or whole-ventricle RT (WVRT) [RR = 3.361, 95% CI (2.126, 5.312)]; both WBRT and WVRT were also with higher recurrence compared with CSI; but no significant difference in recurrence and mortality between WVRT and WBRT. Total 24 studies reported treatment-related acute and/or late toxicity, combination CTx increased acute toxic, and expanded RT field and/or dose increased late toxicity., Conclusion: Based on our findings, focal field RT is not recommended regardless of whether combined with CTx for intracranial pure germinoma. Although CSI is associated with better local control than other reduced-field RT, considering the potential toxicity and pattern of relapse, whole ventricles irradiation is more reasonable for localized or nonmetastatic germinoma. Reduced-dose CSI with or without chemotherapy is effective in metastatic or disseminated IG., 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).)

A ratiometric nanosensor was developed for detecting methyl orange (MO) based on down/up-conversion luminescence achieved by a triplet-triplet annihilation upconversion luminescence (TTA-UCL) system. The probe, utilizing sensitizer and annihilator fluorophores encapsulated in nanomicelles, demonstrated high sensitivity and selectivity for MO detection. The energy transfer from UCL to MO endowed the sensor with responsive capabilities. The unaffected triplet-triplet energy transfer process maintained the phosphorescence signal constant, serving as a reference to construct the ratiometric sensor along with the UCL signal. Additionally, a smartphone-assisted colorimetric detection method was also developed based on the ratiometric sensor, enabling rapid and convenient detection of MO without the need for a spectrometer. The performance of the nanosensor in real water samples confirmed its potential for practical environmental applications., 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.)

Cephalosporin C (CPC) is a critical raw material for cephalosporin antibiotics produced by Acremonium chrysogenum. During fermentation, the oxygen supply is a crucial factor limiting the efficient biosynthesis of CPC. This study demonstrated that the addition of exogenous surfactants significantly increased the dissolved oxygen (DO) level, extracellular catalase content, and final CPC titer. Consequently, we hypothesized and examined a correlation between catalase and CPC biosynthesis in A. chrysogenum through both the exogenous addition of hydrogen peroxide (H₂O₂) and the endogenous modulation of the catA expression level. The results indicated that both the addition of H₂O₂ and the ∆catA mutation exhibited similar fermentation trends, leading to decreased extracellular catalase activity and increased intracellular reactive oxygen species (ROS) content, which resulted in reduced CPC production. Conversely, strains that overexpress varying levels of the catA accelerated hyphal differentiation under DO-limiting conditions, reducing intracellular ROS accumulation and decreasing cellular apoptosis, which stabilized CPC yield during the later stages of fermentation. This study provides a critical foundation for further investigations into the regulatory mechanisms governing CPC biosynthesis in A. chrysogenum., Competing Interests: Declarations. Ethics approval: This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interests: The authors declare no competing financial interest., (© 2024. The Author(s).)

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, triggered a global pandemic with severe medical and socioeconomic consequences. While fatality rates are higher among the elderly and those with underlying comorbidities, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. The aim of our study was to investigate whether the autoimmunity risk gene, PTPN2, which also confers elevated risk to develop inflammatory bowel disease (IBD), affects susceptibility to SARS-CoV-2 viral uptake., Methods: Using samples from PTPN2 genotyped IBD patients, PTPN2-deficient mice, and human intestinal and lung epithelial cell lines, we investigated how PTPN2 affects expression of the SARS-CoV-2 receptor ACE2, and uptake of virus-like particles expressing the SARS-CoV2 spike protein and live SARS-CoV-2 virus., Results: We report that the autoimmune PTPN2 loss-of-function risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry of SARS-CoV-2 spike protein and live virus. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib., Conclusion: Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The integration of crowdsourced data has become central to contemporary built environment studies, driven by the rapid growth in digital technologies and participatory approaches that characterize modern urbanism. Despite its potential, a systematic framework for its analysis remains underdeveloped. This review, conducted in accordance with the PRISMA protocol, examines the use of crowdsourced data in shaping the built environment, scrutinizing its applications, crowdsourcing techniques, methodologies, and comparison with other big data forms. From 226 relevant studies, this study uncovers the evolving thematic landscape of crowdsourced data through a longitudinal analysis (2013-2024), revealing the driving forces that have shifted its representation over time. Additionally, by examining the cultural dimensions and contextual variability, this study demonstrates how identical data is interpreted in markedly different ways across diverse geographic and social contexts. These findings underscore the inmportance of adopting context-sensitive and culturally aware approaches to effectively leverage crowdsourced data in the built environment research. The novelty of this review lies in reframing crowdsourced data not merely as an application tool but as a lens for understanding broader cultural and technological shifts, offering both theoretical and practical insights into its role in the built environment. By advancing our understanding of the unique contributions of crowdsourced data and its complementary role to other big data types, this review provides actionable recommendations for urban planners and policymakers. Ultimately, these findings promote more inclusive and sustainable urban development, fostering cities that better respond to the needs of diverse populations., Competing Interests: Declaration of competing interest The authors, Qiuyi Yang, Bo Zhang, Jiawen Chen, Yang Song and Xiwei Shen (corresponding authors), on behalf of all contributors to this manuscript, declare that there are no financial or personal relationships with other individuals or organizations that could inappropriately influence or bias the content of this paper. None of the authors have any competing interests to disclose in relation to employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, grants, or other funding. Each author has confirmed that they have no conflicts of interest to declare and that the information provided in this statement is accurate and complete., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT)., Methods: HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC)., Results: The populations of CD4 + T cells, CD8 + T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3 + T cells and LAG3 + T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8 + T cells infiltrating in the tumor marginal zone., Conclusion: The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3 + T cells and LAG3 + T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses., 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. Published by Elsevier Ltd.)

Adolescence represents a crucial period for sexual and romantic relationship development, and acquisition of skills and confidence essential for effective sexual consent communication. However, various barriers may interfere with adolescents' belief in their ability (i.e., their self-efficacy) to negotiate consent in practice. This study aimed to investigate the state of adolescents' self-efficacy to ask for consent and explore the influence of romantic relationship communication (a construct comprised of three characteristics: relationship assertiveness skills, positive conflict resolution, and communication awkwardness). Participants were 411 adolescents who had current or past relationships (61% girls, 77% Latine, 79% heterosexual). Participants generally reported above-average levels of self-efficacy to ask for consent ( M  = 4.14 out of 7, SD  = 1.24), with LGBQ+ adolescents exhibiting statistically significantly higher levels of self-efficacy compared to heterosexual adolescents ( M  = 4.51 vs. 4.09, t  = -2.66, p  = .008). Self-efficacy to ask for consent was positively individually related to positive conflict resolution and relationship assertiveness skills, and negatively related to communication awkwardness (all p s < .001). In a path model, romantic relationship communication displayed a statistically significant association with adolescents' self-efficacy to ask for consent, with high positive conflict resolution, low communication awkwardness, and high relationship assertiveness skills being associated with higher self-efficacy to ask for consent. Findings suggest improving adolescents' romantic communication skills may enhance their self-efficacy to ask for consent, and contribute to increased rates of sexual consent communication. Intervention strategies should target multiple levels of influence to promote positive consent cognitions, behaviors, and cultural norms.

The mud crab (Scylla paramamosain) is a commercially significant marine decapod crustacean. Due to its obvious sexual dimorphism, the mechanism of sex differentiation and gonadal development has attracted significant research interest. The Dmrt (double-sex and mab-3 related transcription factor) genes are vital in animal gonadal development and sex differentiation. In the present study, miR-34 was predicted to target the 3' end of Dmrt-1, idmrt-2, Dmrt-3, Dsx and Dmrt-like genes by prediction software, and the interactions between miR-34 and these Dmrt genes were validated by in vivo and in vitro experiments. Dual luciferase assay results indicated that miR-34 mimics/inhibitors co-transfected with plasmid vectors with 3' end of Dmrt-1, idmrt-2, Dmrt-3, Dsx and Dmrt-like, respectively, led to a significant decrease/increase of fluorescence activity in HEK293T cells. In vivo experiments showed that injection of agomir-34 significantly inhibited Dmrt-1, idmrt-2, Dsx and Dmrt-like expression, while injection of antagomir-34 caused the opposite result. However, Dmrt-3 expression was not affected by injection of miR-34 reagents. Meanwhile, the expression of spermatogenesis and testicular development-related molecular marker genes (IAG, foxl2 and vasa) in mud crabs was significantly changed after injecting the miR-34 reagent in vivo. Furthermore, the result of immunoblotting proved that the expression level of Dmrt-like protein can be regulated by miR-34. These results imply that miR-34 is indirectly involved in sex differentiation and testicular development of S. paramamosain by regulating Dmrt-1, idmrt-2, Dsx and Dmrt-like genes., 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.)

Automatic segmentation of blood vessels in fundus images is important to assist ophthalmologists in diagnosis. However, automatic segmentation for Optical Coherence Tomography Angiography (OCTA) blood vessels has not been fully investigated due to various difficulties, such as vessel complexity. In addition, there are only a few publicly available OCTA image data sets for training and validating segmentation algorithms. To address these issues, we constructed a wild-field retinal OCTA segmentation data set, the Retinal Vessels Images in OCTA (REVIO) dataset. Second, we propose a new retinal vessel segmentation network based on spatial and frequency domain networks (SFNet). The proposed model are tested on three benchmark data sets including REVIO, ROSE and OCTA-500. The experimental results show superior performance on segmentation tasks compared to the representative methods., (© 2024 Wiley‐VCH GmbH.)

Subarachnoid hemorrhage (SAH) is a specific type of stroke. Dihydroquercetin (DHQ), a flavonoid, is known for its various pharmacological properties. This study aimed to explore the roles and mechanisms of DHQ in influencing the progression of SAH. A rat SAH model was established using the endovascular perforation technique. Following SAH induction, DHQ was administered orally 1 h later. Assessments included SAH scores, neurological function, brain swelling, blood-brain barrier (BBB) integrity, neuronal damage, apoptosis levels, inflammation, and indicators of ferroptosis using various treatments. The HT22 cells were exposed to hemin to simulate SAH-like conditions under in vitro settings. Cell counting kit-8 assays, flow cytometry, enzyme?linked immunosorbent assay, BODIPY 581/591 C11 staining, western blot analysis, and biochemical kits were employed to evaluate the potential effects of DHQ. Moreover, the mechanisms responsible for the protective effect of DHQ were examined by western blot analysis. The in vivo findings revealed that DHQ mitigated neurological impairments, brain swelling, BBB disruption, and neuronal injury at 24 h post-SAH. DHQ also reduced neuronal degeneration, inflammation, and ferroptosis following SAH. The in vitro findings revealed that DHQ enhanced cell survival and reduced ferroptosis at 24 h following hemin exposure. Mechanistically, DHQ activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in SAH rats and hemin-treated HT22 cells to exert neuroprotective effects. In conclusion, this study reveals that DHQ can effectively decrease BBB permeability, brain edema, neurological dysfunctions, and ferroptosis post-SAH by activating the PI3K/AKT/Nrf2/HO-1 pathway., (© 2024 Wiley Periodicals LLC.)

Sex influences many biological outcomes, but how sex affects hematopoietic stem cell (HSC) aging and hematological disorders is poorly understood. The widespread use of young animal models to study age-related diseases further complicates these matters. Using aged and long-lived BALB/c mouse models, we discovered that aging mice exhibit sex-dependent disparities, mirroring aging humans, in developing myeloid skewing, anemia, and leukemia. These disparities are underlined by sex-differentiated HSC aging characteristics across the population, single-cell, and molecular levels. The HSC population expanded significantly with aging and longevity in males, but this occurred to a much lesser degree in aging females that instead expanded committed progenitors. Aging male HSCs are more susceptible to BCR-ABL1 transformation with faster development of chronic myeloid leukemia (CML) than female HSCs. Additionally, the loss of the aging regulator Sirt1 inhibited CML development in aging male but not female mice. Our results showed for the first time that sex-differentiated HSC aging impacts hematopoiesis, leukemogenesis, and certain gene functions. This discovery provides insights into understanding age-dependent hematological diseases and sex-targeted strategies for the treatment and prevention of certain blood disorders and cancer., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the animal use and biosafety guidelines and regulations. Animal studies were conducted under the approved protocol 16056 by City of Hope Institutional Animal Care and Use Committee. This study did not involve human subjects., (© 2024. The Author(s).)

Objective: Prior researchers have identified distinct differences in functional connectivity neuroimaging characteristics among MDD patients. However, the auxiliary diagnosis and subtype differentiation roles of VMHC values in MDD patients have yet to be fully understood. We aim to explore the separating ability of VMHC values in patients with anxious MDD or with non-anxious MDD and HCs., Methods: We recruited 90 patients with anxious MDD, 69 patients with non-anxious MDD and 84 HCs. We collected a set of clinical variables included HAMD-17 scores, HAMA scores and rs-fMRI data. The data were analyzed combining difference analysis, SVM, correlation analysis and ROC analysis., Results: Relative to HCs, non-anxious MDD patients displayed significant lower VMHC values in the insula and PCG, and anxious MDD patients displayed a significant decrease in VMHC values in the cerebellum&#95;crus2, STG, postCG, MFG and IFG. Compared with non-anxious MDD patients, the anxious MDD showed significant enhanced VMHC values in the PCG. The VMHC values in the insula and cerebellum&#95;crus2 regions showed a better ability to discriminate HCs from patients with non-anxious MDD or with anxious MDD. The VMHC values in PCG showed a better ability to discriminate patients with anxious MDD and non-anxious MDD patients., Conclusion: The VMHC values in the insula and cerebellum&#95;crus2 regions could be served as imaging markers to differentiate HCs from patients with non-anxious MDD or with anxious MDD respectively. And the VMHC values in the PCG could be used to discriminate patients with anxious MDD from the non-anxious MDD patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The durability of the immunogenicity elicited by three doses of mRNA-based BNT162b2 and whole-virus inactivated CoronaVac in patients with neuromuscular diseases, particularly those on immunosuppressive drugs and variants of concern, has not been well-established. Our goal was to evaluate medium-term humoral immunogenicity outcomes after 3 doses of these vaccines. Peripheral blood samples were collected from participants 14-49 days and 155-210 days after administration of the third vaccine dose to assess humoral immune responses through serological assays. The immunogenicity outcomes of each patient were compared to those of three age-matched healthy control participants, ensuring a balanced comparison. Both patients that received 3 doses of BNT162b2 and 10 (90.9%) patients that received CoronaVac seroconverted against wild-type-SARS-CoV-2 virus, showing comparable antibody responses to healthy participants. After 6 months, one patient in BNT162b2 and all four patients in CoronaVac groups maintained seropositivity. The JN-1 specific binding antibody response was lower compared to wild-type virus. The use of corticosteroids did not affect seroconversion rate against wild-type virus or JN.1 variant. BNT162b2 and CoronaVac were immunogenic for neuromuscular diseases patients, maintaining durability after 6 months even for those on corticosteroids. Our data support a rapid immunization series utilizing mRNA-based and whole-virus inactivated vaccines for future pandemic.

Osteoarthritis (OA) is a multifaceted degenerative joint disorder affected by various risk factors such as age, mechanical stress, inflammation, and metabolic influences. These elements contribute to its diverse phenotypes and endotypes, underscoring the disease's inherent complexity. The involvement of multiple tissues and their interplay further complicates OA's investigation. The current limitations in spatial phenotyping technologies, coupled with the intricate web of multifactorial interactions, have hindered the discovery of reliable early diagnostic markers and the development of tailored therapeutic strategies. However, recent advances in spatiotemporal analysis have revolutionised researchers' capacity to explore OA's spatiotemporal dynamics. These advancements provide unprecedented insights into the disease's progression, revealing patient-specific clinical presentations, tissue and joint structure alterations, and microscopic to molecular changes in tissue cell populations and extracellular matrices. This paper summarises the latest developments in utilising state-of-the-art technologies for the deep phenotyping of OA's spatiotemporal variations, emphasising their critical role in elucidating OA's pathophysiology and how this can change clinical practice and advancing personalised treatment approaches, and finally lead to better clinical outcomes.

Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes of de novo lipogenesis. Mouse and human data establish G3P-ChREBP as a new mechanistic component of the Randle Cycle that contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) and forms part of a system that communicates metabolic states from liver to brain in a manner that alters food and alcohol choices. The data provide a framework for understanding FGF21 induction in varied conditions, suggest ways to develop FGF21-inducing drugs, and drug candidates for both lean MASLD and support of urea cycle function in CD.

Biodegradable plastics, regarded as an ideal substitute for traditional plastics, are increasingly utilized across various industries. However, due to their unique degradation properties, they can generate microplastics (MPs) at a faster rate, potentially posing a threat to plant development. This study employed transcriptomics and metabolomics to investigate the effects of polylactic acid microplastics (PLA-MPs) on the physiological and biochemical characteristics of Brassica chinensis L. over different periods. The findings indicated that exposure to varying concentrations of PLA-MPs had distinct influences on the growth and development of Brassica chinensis L. Transcriptomic analysis showed different concentrations of PLA-MPs directly influenced the expression of genes associated with plant hormones, such as SnRK2 and BnaA01g27170D. In addition, it was observed that these PLA-MPs also impacted plant growth and development by modulating the expression of other genes, eg. related to sulfur metabolism and glycerophosphate metabolism. Metabolomic analysis demonstrated alterations levels of metabolites such as L-glutamine, and arginine in response to PLA-MPs, which influenced pathways related to vitamin B6 metabolism, the one-carbon folate pool, glycerophospholipid metabolism, and cysteine. This study offers new insights into the potential impacts of biodegradable microplastics (BMPs) on plants and underscores the need for further investigation into the potentially more significant effects of BMPs on terrestrial ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no know 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.)

With the global implementation of wastewater reuse, accurately assessing the soil ecological risk of chiral pollutants from wastewater necessitates a comprehensive understanding of their enantioselective toxicity to soil animals. Ibuprofen (IBU) is the most prevalent chiral pharmaceutical in municipal wastewater. However, its enantioselective toxicity toward soil animals and the underlying mechanism remain largely unknown. In this study, the toxicity of IBU enantiomers, S -IBU and R -IBU, to earthworms was evaluated at environmentally relevant concentrations (10 and 100 μg/L), simulating wastewater reuse for irrigation. The results demonstrated that IBU adversely affects the growth, reproduction, regeneration, defense systems, and metabolic processes of earthworms, with S -IBU exhibiting stronger toxic effects than R -IBU. The bioavailability assessment revealed that S -IBU was more readily absorbed by earthworms and converted to its enantiomer within earthworms than R -IBU. This is consistent with molecular docking results showing that S -IBU had stronger affinities for functional proteins associated with xenobiotic transport and transformation. The findings of this study highlight that S -IBU poses a higher risk than R -IBU to soil organisms under wastewater reuse scenarios and that the chirality of chemical pollutants in wastewater deserves more attention when implementing wastewater reuse. In addition, our study underscores that the differences in bioavailability and bioactivity may account for the enantioselective toxicity of chiral pollutants.

Sparse data bias, where there is a lack of sufficient cases, is a common problem in data analysis, particularly when studying rare binary outcomes. Although a two-step meta-analysis approach may be used to lessen the bias by combining the summary statistics to increase the number of cases from multiple studies, this method does not completely eliminate bias in effect estimation. In this paper, we propose a one-shot distributed algorithm for estimating relative risk using a modified Poisson regression for binary data, named ODAP-B. We evaluate the performance of our method through both simulation studies and real-world case analyses of postacute sequelae of SARS-CoV-2 infection in children using data from 184 501 children across eight national academic medical centers. Compared with the meta-analysis method, our method provides closer estimates of the relative risk for all outcomes considered including syndromic and systemic outcomes. Our method is communication-efficient and privacy-preserving, requiring only aggregated data to obtain relatively unbiased effect estimates compared with two-step meta-analysis methods. Overall, ODAP-B is an effective distributed learning algorithm for Poisson regression to study rare binary outcomes. The method provides inference on adjusted relative risk with a robust variance estimator., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

Objectives: The detection rate of vancomycin-resistant Enterococcus faecium (VREfm) displayed a dramatically increase in Guangdong, China from 2021 to 2023, for which the molecular epidemiology and genomic characteristics remain largely unexplored. In this study, we investigated the genetic features and epidemiology of VREfm isolates in Guangdong., Methods: A total of 54 Guangdong VREfm isolates were collected from three tertiary hospitals in Guangdong. We preformed antimicrobial susceptibility test, whole genome sequencing, risk factor analysis, and bioinformatics analysis to conduct this research., Results: Our investigation indicated that VREfm isolates were highly clonal and multidrug-resistant ST80 Enterococcus faecium harboring vanA-positive plasmid. The phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) demonstrated that VREfm isolates exhibited minimal genetic similarity to previously reported E. faecium in China, whereas exhibited high genomically similar to an India strain A10290 isolated in 2019 and Hiroshima isolates detected in 2020, indicative of a possible exogeneous import. The genetic environment of cps region showed a novel type of wzy gene cluster involved in capsule polysaccharide (CPS) biosynthesis flanked by ISEf1 and IS16 was identified in VREfm isolates, which displayed a remarkably divergence from the downstream of putative cpsABCD region in other sequence types (STs) E. faecium. Heat map of plasmid-mediated virulence factors suggested several predicted proteins including Cag pathogenetic island proteins existed in VREfm isolates at a high frequency., Conclusions: This study highlighted the importance of ongoing surveillance to track the dynamic dissemination of multidrug-resistant ST80 VREfm isolates harboring multiple virulence genes in Guangdong province, China., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier Ltd.)

Background: With the increasing demand for total hip arthroplasty (THA) and the inevitable trend of orthopedic robots and artificial intelligence in the future, it is necessary to explore the safety and effectiveness of orthopedic robots in THA. Currently, most orthopedic robots are in the early stages of development, and evaluating their clinical efficacy can assist in making informed decisions for practical use., Objective: To explore the advantages of 7 types of robot-assisted THA with respect to 5 indicators., Methods: Literature from databases such as CNKI, PubMed, and Web of Science was retrieved up to July 17, 2024. Literature evaluation was conducted via Review Manager 5.4, and a network meta-analysis was performed via RStudio (version 4.4.1)., Results: A total of 17 studies involving 1741 patients were included. In direct comparisons, the operation time was longer for MAKO (MD = 19; CI = 6.7, 31), TRex (MD = 37, CI = 20, 54) and YUANHUA (MD = 35, CI = 4.2, 66) than for C-THA. The leg length discrepancy (LLD) was smaller for TRex (MD = -3.4, CI = -6.6, -0.36) and RO (MD = -4.3, CI = -8.7, -0.064) than for C-THA. In the comprehensive best probability ranking, operation time [C-THA (96%) > TJ (68%) > RO (53.2%) > MAKO (53%) > LA (45%) > YU (21%) > TR (13%)], blood loss [TJ (89%) > C-THA (50%) > LA (49%) > YU (42%) > MAKO (20%)], LLD [RO (83%) > TR (75%) > MAKO (61%) > TJ (51%) > YU (43%) > JJ (40%) > C-THA (24%) > LA (22%)], HHS [RO (65%) > C-THA (55%) > LA (51%) > TR (50%) > JJ (48%) > YU (46%) > MAKO (37%)], and infection [TJ (77%) > C-THA (67%) > MAKO (44%) > RO (10%)]., Conclusion: Each of the seven types of RA-THA and C-THA has its own advantages, with TJ and RO RA-THA being slightly more prominent. Overall, in terms of safety and effectiveness, RA-THA is generally superior to C-THA, although further development is still needed., Competing Interests: Declarations. Consent for publication: All the authors of this study have given their consent to publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The medicinal fungus Phellinus Igniarius (P. igniarius) has been demonstrated to possess a variety of pharmacological effects, including anti-oxidant, anti-tumor, blood circulation promotion, anti-diarrheal and sedative properties, etc. In order to gain a deeper understanding of the components in P. igniarius extract and its dynamic process in vivo, an ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for the simultaneous determination of 12 major components (nobiletin tangeretin, narirutin, 3,4-dihydroxybenzaldehyde, hesperidin, hispidin, caffeic acid, hispolon, osmundacetone, amygdalin, salvianolic acid B and protocatechuic acid) of P. igniarius extract in rat plasma. The analyses were conducted using an ACQUITY UPLC BEH C18 column with acetonitrile and 0.1 % formic acid (v/v) in aqueous solution as the mobile phases. The intra-day and inter-day precision was less than 12.61 % for all 12 experiments, with a precision range of -11.28-12.25 %. Extraction recovery exhibited a range of 74.03-114.33 %, while the matrix effect demonstrated a range of 83.95-119.28 %. The stability tests demonstrated that the analytes remained stable, with relative standard deviations below 11.65 %. The pharmacokinetic parameters of the 12 compounds in rat plasma after oral administration of P. igniarius extract were successfully determined by the established UPLC-MS/MS method. The findings presented a pivotal foundation for advancing future research on the in vivo processes and mechanisms underlying the effects of P. igniarius extracts., Competing Interests: Declaration of Competing Interest The authors declare that they have no 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.)

PIK-75 (F7) is a potent multikinase inhibitor that targets p110α, DNA-PK, and p38γ. PIK-75 has shown potential as a therapy in preclinical cancer models, but it has not been used in the clinic, at least in part, due to limited solubility. We therefore developed a nanoparticle to encapsulate PIK-75 and enable targeted cellular delivery. Scavenger receptor class B type 1 (SR-B1) is often overexpressed in cancer compared with normal cells, which enables targeting by synthetic lipid nanoparticles with some features of native high-density lipoprotein (HDL), the natural ligand of SR-B1. We investigated the use of organic core (oc) molecular platforms to synthesize HDL-like nanoparticles (oc-HDL NP). Employing an oc, we successfully formulated PIK-75 into oc-HDL NPs. The PIK-75 loaded oc-HDL NP (PIK-75 oc-HDL NP), comprising ∼20 PIK-75 molecules/NP, has similar size, surface charge, and surface composition as oc-HDL NP and natural human HDL. Using prostate cancer (PCa) and cutaneous T-cell lymphoma (CTCL) models known to be sensitive to inhibitors of p110α and p38γ, respectively, we found that PIK-75 oc-HDL NPs specifically targeted SR-B1 to deliver PIK-75 and potently induced cell death in vitro in PCa and CTCL and in vivo in a murine PCa model. Additionally, we found that PIK-75 oc-HDL NP, but not free PIK-75 or oc-HDL NP alone, reduced the IC 50 in the NCI-60 cell line panel and additional pancreatic cancer cell lines. These data demonstrate the first example of drug-loaded oc-HDL NP that actively target SR-B1 and kill cancer cells in vitro and in vivo, encouraging further development and translation to human patients.

Multifunctional organic light-emitting transistors (OLETs), which combine electric-switching and light-producing capabilities into a single device, are attracting increasing interest as promising candidates for new-generation display technology. Despite advancements in the design of organic luminescent materials and the optimization of device geometry configurations, maintaining operating voltage low while enhancing optical performances remains a key challenge in horizontally structured OLETs. Here, a simple and effective interfacial engineering strategy is employed to improve the optical properties of horizontal OLETs operating at low voltage, by introducing ultraviolet ozone (UVO)-induced surface modification on high-k dielectrics. It takes the role to not only control the surface activation states of dielectric layers but also optimize the growth dynamics behavior of channel film benefitting from the strong interfacial interaction between chemically modified dielectric surface and channel seed molecules. The optimized horizontal-channel OLET exhibits a significantly high brightness of 9,484 cd m - 2 , more than 25 times greater than that of untreated OLETs (347 cd m - 2 ), along with a peak EQE of 9.64%, a low operating voltage of 15 V, and good dynamic gate stress stability, outperforming other reported horizontal-channel high-performance OLETs. This work demonstrates that dielectric/semiconductor interface engineering is essential for high-performance transistor-based optoelectronic devices including horizontal OLETs., (© 2024 Wiley‐VCH GmbH.)

Coconut (Cocos nucifera L.) is a key tropical economic tree valued for its fruit flavor, particularly 2-acetyl-1-pyrroline (2AP), a vital aroma metabolite. To enhance high-aromatic coconut breeding efforts, it is essential to deeply understand the hereditary factors governing the production of 2AP. In this study, a genome-wide association analysis identifies 32 loci that exhibit significant associations with 2AP content based on single nucleotide polymorphism (SNP) variations from 168 aromatic coconut germplasm resources. Transcriptome analysis then pinpoints 22 candidate genes near significant loci involved in 2AP metabolism. Proteins encoded by these genes are involved in amino acid metabolism, glycolysis, and secondary metabolism. Among these, Asparagine synthetase coding gene ASN1, Gamma-glutamylcysteine synthetase coding gene GSH1, and UbiA prenyltransferase coding gene UBIA are enriched in the linkage region constructed by significant locus Chr04&#95;61490504. In particular, the SNP mutation of CnASN1 leads to amino acid changes in the functional region of the coding protein, potentially resulting in differences in 2AP content among haplotype populations. Identifying variations in related candidate genes, particularly the gene CnASN1, provides molecular markers closely associated with 2AP synthesis for coconut breeding and offers further insights into the metabolic mechanisms of 2AP., Competing Interests: Conflict of 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 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Purpose: In the United States, there are disparities in access to care for patients with non-small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC)., Methods: This retrospective study used data from the SEER-Medicare-linked database. The cohort included patients (age 66 years or older) diagnosed with aNSCLC (stage III/IV) between March 2015 and December 2017, and they were followed through December 2019. Race/ethnicity was categorized as non-Hispanic (NH)-White, NH-Black, Hispanic, and Other. ICI therapy utilization was determined by identifying any usage of ICI agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and cemiplimab-rwlc) from the Medicare database. Multivariable logistic regression models assessed the association between race/ethnicity and ICI therapy utilization (yes, no). Effect measure modification analyses were conducted by sex, socioeconomic status, and comorbidity., Results: The final sample included 26,836 patients; 76.2% were NH-White, 10.1% NH-Black, 5.7% Hispanic, and 8.0% Other. The overall ICI therapy utilization proportion was 17.8%, varying across ethnicities: NH-Black 14.1%, Hispanic 16.3%, NH-White 18.4%, and Other 18.5%. In comparison with NH-White patients, NH-Black patients were 15% less likely to receive ICI therapy (adjusted odds ratio, 0.85 [95% CI, 0.75 to 0.96]). Furthermore, the association between race/ethnicity and utilization of ICI therapy was modified by comorbidity status, sex, and socioeconomic status., Conclusion: NH-Black patients with aNSCLC were less likely to receive ICI therapy than their NH-White counterparts. Our findings indicate the racial/ethnic disparities in ICI therapy utilization and call for further interventions to optimize access to care., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to https://ascopubs.org/authors. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Dongyu Zhang Employment: Johnson & Johnson/Janssen Stock and Other Ownership Interests: Johnson & Johnson/Janssen Travel, Accommodations, Expenses: Johnson & Johnson/Janssen Estelamari Rodriguez Consulting or Advisory Role: AstraZeneca, Research to Practice, Novartis, Janssen Oncology, Bristol Myers Squibb Foundation, Oncocyte, Regeneron, Amgen, Pfizer, Daiichi Sankyo/AstraZeneca, novocure, Boehringer Ingelheim, g1 ther Yi Guo Consulting or Advisory Role: Merck No other potential conflicts of interest were reported. Yi Guo Consulting or Advisory Role: Merck No other potential conflicts of interest were reported. Yi Guo Consulting or Advisory Role: Merck No other potential conflicts of interest were reported., (© 2024 by American Society of Clinical Oncology.)

Understanding the osteochondral junction, where non-mineralised cartilage and mineralised bone converge, is crucial for joint health. Current sample preparation techniques are insufficient for detailed spatial hyperspectral imaging analysis. Using the enhanced Kawamoto method, we used the super cryo embedding medium's temperature-dependent properties to transfer high-quality tissue samples onto slides for spatial imaging analysis. We transferred osteochondral samples using a tape-free system and successfully tested them in hematoxylin and eosin (HE), Safranin-O, nanomechanical assessments and nano-Fourier transform infrared (FTIR) mapping. This protocol elucidates the structural and elemental gradients, mechanical characteristics and distinctive biochemical layering, making it a useful tool for analysing biochemical properties' co-distribution in healthy and diseased situations., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diamond exhibits nontrivial hardness and abrasion, ultra-high thermal conductivity, and light transmission over a wide wavelength range. All these properties are anisotropic. There is considerable literature on the synthesis of large-sized monocrystalline diamonds but the synthesis of highly oriented monocrystalline diamonds is limited. Here, [100] oriented monocrystalline needle-like diamonds are successfully synthesized with an aspect ratio of up to 14 by controlling the temperature gradient and carbon concentration gradient using FeCo alloy as the catalyst at ≈5.8 GPa and 1473 K. The distinctive morphology and microstructure of needle-like diamonds are characterized using Scanning Electron Microscopy, X-ray diffraction, and Focused Ion Beam-Transmission Electron Microscopy. A four-stage growth model is established to elucidate the growth mechanism along the [100], which sheds light on the synthesis of diamonds with predetermines crystal orientations. Increasing the aspect ratio of needle-like diamonds further may enable the development of diamond fibers and assist in the fabrication of laser diamonds with specific orientation requirements., (© 2024 Wiley‐VCH GmbH.)

Microbial biofilms provide advantages in fermentation processes. However, Corynebacterium glutamicum (C. glutamicum) usually exhibits relatively poor biofilm formation compared to other industrial strains. To develop a biofilm-enhanced fermentation process for C. glutamicum, seven genes potentially related to biofilm formation in C. glutamicum were systematically investigated, which include ppk2B, glgC, virB11, cslA, NCgl2909, NCgl0350 and exeR. Deletion of the NCgl0350, NCgl2909 genes and heterologous expression of the cslA gene were found to increase biofilm amounts by 16.9%, 21.2% and 135%, respectively, compared to the wild-type strain. Meanwhile, the production of L-lysine by engineered strains was assessed in biofilm-based continuous fermentation. The most notable result was observed for the cslA-expressing strain, which produced an average of 26.1% higher L-lysine compared with that of wild-type strain in 6-L bioreactors. In conclusion, this study offers valuable insights into the biofilm formation in C. glutamicum and its application in continuous fermentation processes., 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.)

Lupus nephritis (LN) is a common clinical complication of systemic lupus erythematosus (SLE). Proliferative lupus nephritis represents the gravest form of LN, and since effective drugs for its treatment are still lacking, tyrosine kinase inhibitors (TKIs) find extensive clinical utility due to their notable impact on suppressing cell proliferation and may serve as potential drugs for LN treatment. However, previous studies on the effects of TKI on LN have been controversial. Ponatinib, a third-generation TKI, lacks studies on its role in LN. This study aimed to investigate the impact of the ponatinib on LN. MRL/lpr mice were evaluated for renal function, autoimmune markers and histopathological changes after oral administration of ponatinib. RNA-seq analysis was performed to explore the molecular pathways involved in ponatinib-induced kidney injury. Ponatinib uniquely exacerbated renal damage in MRL/lpr mice, evidenced by a decline in renal function and acute pathological changes, without affecting lupus-related autoimmune markers. Differential expressed genes analysis and functional enrichment implicate ponatinib-induced renal damage in MRL/lpr mice associated with adiponectin. Furthermore, we verified ponatinib signaling the PI3K/AKT pathway through PDGFRα, potentially influencing high molecular weight adiponectin (HMW ADIPOQ) expression and exacerbating renal damage. In conclusion, this study demonstrates that ponatinib can up-regulate HMW ADIPOQ expression via the PI3K/AKT pathway by inhibiting PDGFRα phosphorylation, highlighting the potential nephrotoxic effects of ponatinib in lupus-prone mice, and underscoring the importance of monitoring renal function in systemic autoimmune diseases patients receiving ponatinib., 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. Published by Elsevier Inc.)

The inefficient biodegradation and incomplete mineralization of nitrogenous heterocyclic compounds (NHCs) have emerged as a pressing environmental concern. The top-down design offers potential solutions to this issue by targeting improvements in community function, but the ecological linkages between selection strength and the structure and function of desired microbiomes remain elusive. Herein, the integration of metagenomics, culture-based approach, non-targeted metabolite screening and enzymatic verification experiments revealed the effect of enrichment concentration on the top-down designed benzothiazole (BTH, a typical NHC)-degrading consortia. Significant differences were observed for the degradation efficiency and community structure under varying BTH selections. Notably, the enriched consortia at high concentrations of BTH were dominated by genus Rhodococcus, possessing higher degradation rates. Moreover, the isolate Rhodococcus pyridinivorans Rho48 displayed excellent efficiencies in BTH removal (98 %) and mineralization (∼ 60 %) through the hydroxylation and cleavage of thiazole and benzene rings, where cytochrome P450 enzyme was firstly reported to participate in BTH conversion. The functional annotation of 460 recovered genomes from the enriched consortia revealed diverse interspecific cooperation patterns that accounted for the BTH mineralization, particularly Nakamurella and Micropruina under low selection strength, and Rhodococcus and Marmoricola under high selection strength. This study highlights the significance of selection strength in top-down design of synthetic microbiomes for degrading refractory organic pollutants, providing valuable guidance for designing functionally optimized microbiomes used in environmental engineering., 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. Published by Elsevier Ltd.)

Paeonol is a principle bioactive compound separated from the root bark of Cortex Moutan and has been shown to confer various biological functions, including antineuroinflammation and neuroprotection. Inflammation, blood-brain barrier (BBB), permeability, and apoptosis are three major underlying mechanisms involved in early brain injury (EBI) postsubarachnoid hemorrhage (SAH). This study aimed to detect the roles and mechanisms of paeonol in EBI following SAH. A SAH model was established by an endovascular perforation method in Sprague-Dawley rats. The localizations of HMGB1 and p65 were identified by immunofluorescence staining. Protein levels were measured by western blot analysis. The serum levels of HMGB1 and the levels of inflammatory cytokines in the brain cortex were evaluated by ELISA. Hematoxylin and eosin staining was conducted to detect neuronal degeneration. Brain water content and Evans blue extravasation were assessed to determine EBI. Neuronal apoptosis was examined by TUNEL. Paeonol deacetylated HMGB1 by upregulating SIRT1 level. SIRT1 inhibition attenuated the protective effects of paeonol against neurological dysfunctions, brain edema, and BBB disruption. SIRT1 inhibition rescued the paeonol-induced inhibition in inflammatory response. The paeonol-induced decrease in neuronal apoptosis was restored by SIRT1 inhibitor. The paeonol-mediated deactivated TLR4/MyD88/NF-κB pathway was activated by SIRT1 inhibitor. Paeonol alleviates the SAH injury in rats by upregulating SIRT1 to inactivate the HMGB1/TLR4/MyD88/NF-κB pathway., (© 2024 Wiley Periodicals LLC.)

Competing Interests: The authors declare that they have no conflict of interest.

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in pathogenesis of age-related cataract (ARC), causing significant visual impairment. Apoptosis of porcine granulosa cells mediated by MMP2 is linked to DNA damage. The current study aimed to investigate the potential mechanism of MMP2 in DNA damage, apoptosis and senescence of lens epithelial cells caused by oxidative stress. HLE-B3 cells were treated with different doses of H 2 O 2 for 24 h, and CCK-8 was used to detect cell viability. Furthermore, western blotting was used to detect the expressions of MMP2, Bcl2, Bax, cleaved caspase3, γ-H2AX, p16, p21, and TIMP2. DCFH-DA staining was used to assess ROS levels. Moreover, EdU staining was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. Then, 15A3 immunofluorescence staining and γ-H2AX staining were used to detect DNA damage. In addition, SA-β-gal staining was used to observe cell senescence. The present findings suggest that oxidative stress triggers damage to LECs viability and elevates the expression of MMP2. Furthermore, MMP2 interference attenuates H 2 O 2 -induced active damage, apoptosis, DNA damage, and cellular senescence in LECs. Additionally, TIMP2 expression is down-regulated in H 2 O 2 -induced LECs, which suppresses the expression of MMP2 induced by H 2 O 2 . These findings highlight the crucial role of MMP2 and TIMP2 in the modulation of oxidative stress-induced cellular responses in LECs. Collectively, TIMP2 alleviates H 2 O 2 -induced lens epithelial cell viability damage, apoptosis, DNA damage and cell senescence in LECs by inhibiting MMP2., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests. Patient consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic submucosal dissection (ESD) is commonly used to treat early gastric cancer (EGC). The effects of Helicobacter pylori (HP) infection on ESD and the potential benefits of preoperative eradication of HP remain unclear. The study aims to evaluate the impact of HP infection on bleeding and lesion detection during ESD in patients with EGC., Methods: We retrospectively analyzed 634 consecutive patients who underwent ESD for EGC at our center between January 2018 and January 2023. Logistic regression was used to assess the impact of HP infection status on intraoperative bleeding and lesion detection rates. We developed a predictive model based on selected indicators and evaluated its performance using the ROC curve., Results: HP-positive patients experienced a higher rate of intraoperative bleeding (28.8%) compared with HP-negative patients (8.9%) (P < 0.001). HP-positive patients also had longer procedure time (median: 58.5 vs. 50.0 min, P < 0.001) and postoperative hospital stays (median: 4.35 vs. 4.07 days, P = 0.036). Multivariate analysis identified HP-positive (OR = 4.84), multiple lesions (OR = 1.81), specimen size > 40 mm (OR = 3.67), and submucosal invasion (OR = 2.27) as independent risk factors for intraoperative bleeding. The predictive model achieved an AUC of 0.807 (95%CI 0.761-0.852), with a sensitivity of 72.1% and specificity of 75.9%. Preoperative HP eradication was associated with an increased rate of lesion detection (OR = 2.82)., Conclusions: Eradicating HP before ESD in patients with EGC reduces intraoperative bleeding and improves lesion detection. Preoperative HP eradication is therefore recommended in patients with EGC., Competing Interests: Declarations. Disclosures: Dr. Rui Wu, Dr. Tian Yang, Dr. Liangliang Shi, Dr. Xiwei Ding, Dr. Xiaotan Dou, Dr. Yi Wang, Dr. Min Chen, Dr. Lei Wang, Prof. Guifang Xu, Prof. Xiaoping Zou, and Dr. Wei Zhang have no conflicts of interest or financial ties to disclose. Ethical approval: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethical Committee of Nanjing Drum Tower Hospital (NO. 2023-674-02), which was registered on the Clinical Trials website (ChiCTR2400083166). Written informed consent for examination and treatment was obtained from all patients before the procedure. Informed consent for the study was waived due to its retrospective and anonymous nature., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cardiotoxicity is a serious adverse reaction during drug treatment. The cardiac human ether-a-go-go-related gene (hERG) channels play a crucial role in driving cardiac action potential repolarization and are a key target for drug-induced cardiac toxicity. Chelerythrine (CHE) has anticancer effects on various human cancer cells. But little is known about its drug safety currently. The purpose of this study is to explore the key mechanism of cardiac toxicity induced by CHE under pathological conditions. CHE and hypoxia prolonged QT interval and action potential duration compared with control group in guinea pigs, as measured by BL-420S biological acquisition and processing system in conjunction with optical mapping technology. hERG current was measured by patch-clamp technique, and the interaction between ubiquitin molecules and hERG channels was assessed using immunoprecipitation method at the molecular level. The colocalization of proteins and the function of lysosomes were determined via confocal laser scanning microscopy. Further research indicates that CHE enhances the ubiquitination process of hERG proteins by catalyzing the formation of K63 ubiquitin chains, the ubiquitination modification disrupts hERG channel homeostasis, and promotes the degradation of the channel. Mechanistically, CHE accelerates the degradation of hERG channels through lysosomes via HDAC6, which may easily induce cardiotoxicity caused by prolonged QT interval under hypoxic conditions., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure All authors disclosed no financial relationships relative to the content of this work. Commentary In the current case, ESD was performed by use of a modified clip-and-snare traction technique. This method involves prelooping a snare at the endoscope tip, attaching a clip to the lesion's mucosal flap, and manipulating the snare to grasp the clip. This technique offers improved snare delivery, flexible movement, multipoint traction, and shorter procedure times. The lesion was removed en bloc, revealing moderately differentiated squamous cell carcinoma. Postprocedure adverse events included nasal regurgitation and hypernasal speech, which were managed conservatively. No recurrence was observed at 6 and 12 months. This case highlights a challenging ESD procedure in a delicate location, successfully executed by use of an innovative traction method. Traction ESD will continue to evolve and will result in easier adoption and performance of ESD procedures. Marina Kim MD, Assistant Professor of Medicine, St. Louis University School of Medicine, St. Louis, Missouri, USA Mohamed O. Othman, MD, GIE Senior Associate Editor

The hippocampus is crucial for forming new episodic memories. While the encoding of spatial and temporal information (where and when) in the hippocampus is well understood, the encoding of objects (what) remains less clear due to the high dimensions of object space. Rather than encoding each individual object separately, the hippocampus may instead encode categories of objects to reduce this dimensionality. In this study, we developed and applied a combined experimental-modeling approach to investigate how the hippocampus encodes visual memory categories in humans. We recorded spikes from hippocampal CA3 and CA1 neurons in 24 epilepsy patients performing a visual delayed match-to-sample (DMS) task involving five image categories. An ensemble multi-temporal-resolution classification model was employed to decode these visual memory categories from the hippocampal spiking activity with moderate numbers of trials. This model enables the identification of the spatio-temporal characteristics of hippocampal encoding through its interpretable representations. Using this model, we estimated the optimal temporal resolutions for decoding each visual memory category for each neuron in the ensemble. Results indicate that visual memory categories can be decoded from hippocampal spike patterns despite the short data length, supporting the presence of category-specific coding in the human hippocampus. We found that hippocampal neuron ensembles encode visual memory categories in a distributed manner, akin to a population code, while individual neurons use a temporal code. Additionally, CA3 and CA1 neurons exhibit similar and redundant information regarding visual memory categories, likely due to the strong and diffuse feedforward synaptic connections from the CA3 region to the CA1 region.

The plant peptide-containing sulfated tyrosine (PSY) family plays critical roles in plant cell proliferation and stress responses. However, the functional characterization of the PSY peptide family in wheat remains unclear. This study systematically identified a total of 29 TaPSY genes at the genome-wide level, classifying them into six subgroups based on PSY-like motifs. These peptides contain a highly conserved active peptide domain, closely resembling the Arabidopsis AtPSY1 motif. All TaPSY homologs are predicted to have a sulfated tyrosine catalyzed by plant tyrosylprotein sulfotransferase (TPST). The TaPSY genes displayed distinct expression patterns across various tissues, with most genes showing higher expression levels in roots and stems. Synthetic sulfated TaPSY peptides enhanced root growth in both wild-type Arabidopsis and the tpst-1 mutant plants. In wheat, exogenous application of TaPSY peptides also promoted root growth, with the synthetic TaPSY5 peptide affecting reactive oxygen species levels in wheat taproots to stimulate primary root growth. Furthermore, transgenic Arabidopsis plants overexpressing TaPSY10 exhibited longer primary roots and increased lateral root numbers. These findings provide insights into the physiological roles of TaPSY peptides in regulating wheat root growth., Competing Interests: The authors declare no conflicts of interest.

A pivotal approach in engineering artificial peripheral nerve sheaths encompasses the augmentation of the regenerative microenvironment via the manipulation of Schwann cells (SCs). Our investigation employed single-cell sequencing analysis to elucidate the potential functions of Schwann cells and the Wnt pathway in facilitating peripheral nerve regeneration. In vitro studies showed that activating the Wnt signaling pathway promotes the transition to repair SCs, boosting their growth, movement, and immune functions. To better understand the peripheral nerve regeneration environment, we created a polymer scaffold using ammonization and electrospinning. The Wnt3a protein was incorporated into the polycaprolactone (PCL) electrospun fiber surface. In a rat sciatic nerve defect model, the Wnt3a-modified scaffold showed better nerve repair outcomes than traditional electrospun scaffolds. After a week, the test group showed better immune regulation and angiogenesis, with a significant increase in axon growth rate observed after 3 weeks. Three-month-long animal experiments revealed notable improvements in neuroelectrophysiology, reduced organ atrophy, and enhanced sciatic nerve recovery. In this nerve defect model, Wnt3a-modified neural scaffolds achieved repair effects.

Changes in lung and gut microbial communities have been associated with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate correlations between microbial changes in the lung and gut and host physiological indices in an IPF model, exploring potential mechanisms of the lung-gut axis in IPF pathogenesis. IPF model rats were established via trans-tracheal injection of bleomycin, with assessments of hematological indices, serum cytokines, lung histopathology, and microbiome alterations. Significant differences in microbial structure and composition were observed in the IPF model compared to controls, with 14 lung and 7 gut microbial genera showing significant abundance changes. Further analysis revealed 20 significant correlations between pulmonary and gut genera. Notably, 11 pairs of correlated genera were linked to the same IPF-related physiological indices, such as hydroxyproline, mean corpuscular volume (MCV), and red cell distribution width-standard deviation (RDW-SD). We identified 24 instances where a lung and a gut genus were each associated with the same physiological index, forming "lung genus-index-gut genus" relationships. Mediation analysis showed that indices like hydroxyproline, MCV, and RDW-SD mediated correlations between 10 lung genera (e.g., Cetobacterium, Clostridium XVIII ) and the gut genus Allobaculum. This study first describes gut-lung microbial interactions in pulmonary fibrosis. Mediation analysis suggests pathways underlying "lung genus-host index-gut genus" and "gut genus-host index-lung genus" correlations, thus providing clues to further elucidate the mechanisms of the "gut-lung axis" in IPF pathogenesis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was conducted with approval from the Ethics Committee of Minzu University of China (ECMUC2023006AO)., (© 2024. The Author(s).)

Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients' lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Gentamicin, an aminoglycoside antibiotic, is generated by a few species within the genus Micromonospora and has garnered significant attention due to its broad-spectrum efficacy in combating numerous infectious diseases. Comprising a complex array of closely related aminoglycoside compounds, the gentamicin B and C complexes emerge as particularly pertinent in clinical contexts. This review outlines the latest advancements in the biosynthesis and production of gentamicin, commencing with a comprehensive overview of its biosynthetic pathway. Subsequently, the article encapsulates a spectrum of strategies currently deployed to augment gentamicin yields. These strategies include mutation screening, molecular biological techniques, and optimization of the fermentation process. Moreover, numerous methods have been documented for detecting gentamicin across a range of matrices, underscoring the significance of precise quantitative analysis. Finally, the review furnishes an exhaustive market analysis and future outlook, elucidating prevailing trends and challenges within the gentamicin industry. Overall, this article serves as a pivotal resource for researchers and professionals engaged in gentamicin research, furnishing a meticulous introduction to efficient synthesis technologies and diverse applications, alongside presenting innovative concepts and methodologies aimed at increasing gentamicin production., 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.)

Reducing the time before the flowering stage in coconut ( Cocos nucifera L.) trees greatly influences yield, yet the mechanisms driving the switch from vegetative to reproductive growth are not well understood, especially the role of phosphorus in this transition. In this study, dwarf coconut plants of the same cultivation age were selected and categorized into the vegetative phase (VP) or the reproductive phase (RP). By examining the phenotypic traits, nutrient variations in the roots and soil, and the transcriptional expression of relevant genes in the roots across both phases, we investigated the potential mechanisms driving the transition from the VP to the RP in coconuts. The shoots of coconuts in the RP were significantly taller compared to those in the VP. Moreover, the phosphorus concentration in the roots of coconuts during the RP was 1.31 times higher than in the VP, which may be linked to the significant upregulation of the PT1 genes AZ11G0219160 and AZ02G0034860 in the roots of coconuts in the RP. In addition, all phosphorus-containing metabolites in the roots during the RP showed a significant increase, particularly those related to long-chain fatty acids and ribonucleotide metabolites. This suggests that coconut roots may facilitate the progression from vegetative to reproductive growth by enhancing phosphorus uptake via PT1s and promoting the synthesis and accumulation of phosphorus-containing metabolites.

Background/objectives: Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have the potential to enhance mucosal immunity. However, delivering vaccines via the nasal mucosa requires overcoming complex physiological barriers. The aim of this study is to modify PEGylated lipids to enhance the mucosal immune efficacy of the vaccine., Methods: The PEGylated lipid component of lipid nanoparticle (LNP) delivery vectors was modified with chitosan or mannose to generate novel LNPs that enhance vaccine adhesion or targeting on mucosal surfaces. The impact of the mRNA encoding the receptor-binding domain of Omicron BA.4/BA.5 on the immune response was examined., Results: Compared to the unmodified LNP group, the IgG and IgA titers in the chitosan or mannose-modified LNP groups showed an increasing trend. The chitosan-modified group showed better effects. Notably, the PEGylated lipid with 1.5 mol% of chitosan modification produced high levels of IgG1 and IgG2a antibodies, promoting Th1/Th2 responses while also generating high levels of IgA, which can induce stronger cellular immunity, humoral immunity, and mucosal immunity., Conclusions: The 1.5 mol% of chitosan-modified LNPs (mRNA-LNP-1.5CS) can serve as a safe and effective carrier for intranasal mRNA vaccines, offering a promising strategy for combating the Omicron variant.