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Chean Yeah Yong,1 Swee Keong Yeap,2 Kok Lian Ho,3 Abdul Rahman Omar,2,4 Wen Siang Tan1,2 1Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, 2Institute of Bioscience, 3Department of Pathology, Faculty of Medicine and Health Sciences, 4Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future. Keywords: matrix 2 ectodomain, nodavirus capsid, virus-like particle, fusion protein, subunit vaccine, immunogenicity

Afterglow materials have garnered significant interest due to distinct photophysical characteristics. However, it is still difficult to achieve long afterglow phosphorescence from organic molecules due to aggregation-caused quenching (ACQ) and energy dissipation. In addition, most materials reported so far have long afterglow emission only at room or even low temperatures, and mainly use UV light as an excitation source. In this work, we report a strategy to achieve high temperature long afterglow emission through the assembly of isolated 0D metal-organic cages (MOCs). In which, both ACQ and phosphorescence quenching effects are effectively mitigated by altering the stacking mode of organic chromophores through orthogonally anchoring into the edges of cubic MOCs. Furthermore, improvement in molecular rigidity, promotion of spin-orbit coupling and broadening of the absorption range are achieved through the MOC-engineering strategy. As a result, we successfully synthesized MOCs that can produce afterglow emission even after excitation by WLEDs at high temperatures (380 K). Moreover, the MOCs are capable of generating afterglow emissions when excited by mobile phone flashlight at room temperature. Given these features, the potential applications of MOCs in the visual identification of explosives, information encryption and multicolor display are explored., (© 2024 Wiley-VCH GmbH.)

Significant research efforts have been devoted to improving the efficiency of catalytic carbon monoxide (CO) oxidation over α-Fe 2 O 3 -based catalysts, but details of the underlying mechanism are still under debate. Here we apply the ab initio thermodynamic method (AITM) within the density functional theory framework to investigate the phase diagram of α-Fe 2 O 3 (0001) surfaces with various terminations and the catalytic mechanism of CO oxidation on these surfaces. By extending the conventional AITM to consider the charge state of surface defects, we build the phase diagram of α-Fe 2 O 3 (0001) surfaces in relation to the Fermi energy as well as the oxygen chemical potential, which makes it possible to explain the influence of point defects on the surface morphology and to predict the existence of the experimentally observed functional sites such as the ferryl group (FeO) and oxygen vacancies. Our calculations show that the surface with the ferryl-termination exhibits the highest catalytic activity for CO oxidation with remarkably low activation energy (0.05 eV) and the largest exothermic reaction energy, while other surfaces with different terminations are inadequate with relatively high activation energies. Moreover, it is revealed that a Fermi energy increase by means of intrinsic or extrinsic n-type doping is beneficial to the formation of ferryl-termination under both oxygen-rich and oxygen-poor conditions, which promotes the catalytic oxidation of CO via the Eley-Rideal (E-R) mechanism only (O-rich) or in combination with the Mars-van Krevelen (MvK) mechanism (O-poor). Meanwhile, under the O-poor conditions, a Fermi energy decrease by p-type doping facilitates the formation of oxygen vacancies and the CO oxidation might be promoted via the MvK mechanism which is less effective with higher activation energy than the E-R mechanism. Our work provides new fundamental insights into CO oxidation chemistry and mechanisms, thereby contributing to the design of new catalysts with high performance and low cost.

Background: The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation of cell growth, tissue homeostasis, and apoptosis. Morusin, a compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple signaling pathways, including the PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, and apoptosis pathways. This study explores the effects of morusin on YAP activation and its implications for apoptosis resistance., Results: Our investigation revealed that morusin induces transient YAP activation, characterized by the dephosphorylation of YAP at S127 and nuclear localization, followed by gradual rephosphorylation in multiple cancer cells. Notably, this activation occurs independently of the canonical Hippo pathway and involves the LATS1/2, MINK1, and MAPK pathways during the YAP inactivation stage. Furthermore, morusin-induced stress granule formation was significantly impaired in YAP/TAZ-depleted cells, suggesting a role in apoptosis resistance. Additionally, the expression of constitutively active MINK1 maintained YAP activation and reduced apoptosis, indicating that prolonged YAP activation can enhance resistance to cell death., Conclusions: These findings suggest that YAP/TAZ are crucial in resistance to morusin-induced apoptosis, and targeting YAP/TAZ could enhance the anti-cancer efficacy of morusin. Our study provides new insights into the molecular mechanisms of morusin, highlighting potential therapeutic strategies against cancer by disrupting apoptosis resistance., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Polymeric membranes with great processability are attractive for the H 2 /CO 2 separation required for hydrogen production from renewable biomass with carbon capture for utilization and sequestration. However, it remains elusive to engineer polymer architectures to obtain desired sub-3.3 Å ultramicropores to efficiently sieve H 2 from CO 2 . Herein, we demonstrate a scalable way of carbonizing polybenzimidazole (PBI) at low temperatures, followed by vapor phase infiltration (VPI) to atomically narrow ultramicropores throughout the films, forming hybrid organic-inorganic carbon molecular sieves (CMSs). One VPI cycle (100 s) for the PBI carbonized at 500 °C remarkably increases H 2 /CO 2 selectivity from 9.6 to 83 at 100 °C, surpassing Robeson's upper bound. The CMS demonstrates a stable H 2 /CO 2 separation performance when challenged with simulated syngas streams and can be fabricated into thin-film composite membranes, outperforming state-of-the-art membranes. The scalable approach can be ubiquitous to molecularly fine-tune ultramicropores of leading polymeric membranes to further improve their size-sieving ability and thus separation efficiency.

Background: Gastrointestinal endoscopy has been widely used in the diagnosis and treatment of gastrointestinal diseases. A great many of studies on gastrointestinal endoscopy have been done., Aim: To analyze the characteristics of top 100 cited articles on gastrointestinal endoscopy., Methods: A bibliometric analysis was conducted. The publications and their features were extracted from the Web of Science Core Collection, Science Citation Index-Expanded database. Excel, Web of Science database and SPSS software were used to perform the statistical description and analysis. VOSviewer software and MapChart were responsible for the visualizations., Results: The top 100 cited articles were published between 1976 and 2022. The guidelines (52%) and clinical trials (37%) are the main article types, and average publication year of the guidelines is much later than that of the clinical trials (2015 vs 1998). Among the clinical trials, diagnostic study (27.0%), cohort study (21.6%), case series (13.5%) and cross-sectional study (10.8%) account for a large proportion. Average citations of different study types and designs of the enrolled studies are of no significant differences. Most of the 100 articles were published by European authors and recorded by the endoscopic journals (65%). Top journals in medicine, such as the Lancet , New England Journal of Medicine and JAMA , also reported studies in this field. The hot spots of involved diseases include neoplasm or cancer-related diseases, inflammatory diseases, obstructive diseases, gastrointestinal hemorrhage and ulcer. Endoscopic surgery, endoscopic therapy and stent placement are frequently studied., Conclusion: Our research contributes to delineating the field and identifying the characteristics of the most highly cited articles. It is noteworthy that there is a significantly smaller number of clinical trials included compared to guidelines, indicating potential areas for future high-quality clinical trials., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Next-generation sequencing (NGS) cancer profiling has gained traction in routine clinical practice in South Korea. Here, we evaluated the use of NGS testing and genomically-matched therapies for patients with advanced solid tumors in a real-world clinical practice. We analyzed results from NGS cancer panel tests (SNUBH pan-cancer version 2) ordered from June 2019 to June 2020. Genomically-matched treatment was determined based on the novel information obtained from NGS testing, while results from conventional molecular tests were excluded. A total of 990 patients were included in the analysis (median age: 62, Stage IV: 82.5%). Using the Association for Molecular Pathology genetic variant classification system, we found that 257 (26.0%) patients harbored tier I variants, and 859 (86.8%) patients carried tier II variants. Among the tier I cases, the most frequently altered genes we detected were KRAS (106 patients, 10.7%), followed by EGFR (27 patients, 2.7%) and BRAF (17 patients, 1.7%). Of patients with tier I variants, 13.7% received NGS-based therapy as follows: Thyroid cancer (2/7, 28.6%), skin cancer (2/8, 25.0%), gynecologic cancer (7/65, 10.8%), and lung cancer (12/112, 10.7%). Of 32 patients with measurable lesions who received NGS-based therapy, 12 (37.5%) achieved a partial response, and 11 (34.4%) achieved stable disease. The median treatment duration was 6.4 months (95% CI, 4.4-8.4), and the median OS was not reached. In conclusion, NGS tumor profiling was successfully implemented in real-world clinical practice. This enabled the use of molecular profiling-guided therapy which improved survival outcome of selected patients., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The Institutional Review Board of SNUBH approved this study (IRB no. B-2010-645-106) and waived the requirement for written informed consent from the participants because of the retrospective nature of this study. This study was conducted in accordance with the principles of the Declaration of Helsinki, and all study procedures were conducted following the relevant guidelines and regulations., (© 2025. The Author(s).)

Multimodal study of Alzheimer's disease (AD) dorsolateral prefrontal cortex (DLPFC) showed AD-related aberrant intron retention (IR) and proteomic changes not observed at the RNA level. However, the role of sex and how IR may impact the proteome are unclear. Analysis of DLPFC transcriptome showed a clear sex-biased pattern where female AD had 1645 elevated IR events compared to 80 in male AD DLPFC. Increased IR is correlated with lower mRNA levels, suggestive of nonsense-mediated mRNA decay. Two hundred thirty-three mRNAs with elevated IR in females were curated AD genes enriched for ubiquitin-like protein ligase and Tau protein binding. Increased IR genes in combined sex and female AD cohorts showed significant changes in their protein expression patterns with 11%-24% of them differential expressed proteins (DEP), alluding to the regulation of AD proteome by IR independent of RNA level. Upregulated DEPs in male AD were linked to RNA splicing that may prevent aberrant IR, whereas in female AD, they overlapped significantly more with the MAPK/metabolism module associated with cognitive decline. IR genes appeared to be significantly downregulated in specific female AD inhibitory and excitatory neurons compared to control. Differentially retained introns in female AD have elevated H3K27ac marks, strong CTCF binding at their flanking exons, and enriched for PABPC1 motif. Given that H3K27ac is repressive over gene bodies in aged brain and CTCF impedes transcription elongation, their binding patterns can delay co-transcriptional recruitment of spliceosome to cause IR, which may in turn contribute to different trajectories of AD pathology in women., (© 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Hemophilia A (HA) is caused by mutations in coagulation factor VIII (FVIII). Genome editing in conjunction with patient-derived induced pluripotent stem cells (iPSCs) is a promising cell therapy strategy, as it replaces dysfunctional proteins resulting from genetic mutations with normal proteins. However, the low expression level and short half-life of FVIII still remain significant limiting factors in the efficacy of these approaches in HA. Here, we constructed a functionally enhanced FVIII variant, F309S/E1984V-mutated B domain-deleted (BDD)-FVIII (FE-FVIII), with increased activity and stability. We inserted FE-FVIII with a human elongation factor-1 alpha (EF1α) promoter into the AAVS1 locus of HA patient-derived iPSCs via CRISPR/Cas9 (D10A) nickase to ensure expression in any cell type. FE-FVIII was expressed not only in undifferentiated FE-FVIII-inserted (FE-KI) iPSCs but also in endothelial cells (ECs) differentiated from them in vitro. Compared with mice transplanted with wild-type BDD-FVIII-containing ECs, immunocompetent HA mice intravenously transplanted with FE-KI ECs presented a 2.12-fold increase in FVIII activity in the blood and an approximately 20% greater survival rate after hemorrhagic tail injury. For sustained efficacy, FE-KI ECs were subcutaneously transplanted into immunodeficient HA mice, resulting in amelioration of the hemophilia phenotype for more than 3 months. This strategy can improve FVIII function and may provide a universal therapeutic approach for treating HA., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Despite recent advances, improvements to long-term survival in metastatic carcinomas, such as pancreatic or ovarian cancer, remain limited. Current therapies suppress growth-promoting biochemical signals, ablate cells expressing tumor-associated antigens, or promote adaptive immunity to tumor neoantigens. However, these approaches are limited by toxicity to normal cells using the same signaling pathways or expressing the same antigens, or by the low frequency of neoantigens in most carcinomas. Here, we report a fundamentally different strategy for designing safer and more effective anti-cancer therapies through the sensing of cancer-driving biochemical signals and their rewiring to virotherapeutic activation. Specifically, we rationally engineer a RNA vector to self-replicate and cause cytotoxicity in cancer cells exhibiting hyperactive HER2 (ErbB2), but not in normal cells with normal HER2 signaling. Compared to a widely tested virotherapeutic from the same vector family, our hyperactive ErbB2-restricted RNA vector (HERV) exhibits lower toxicity and greater activity against metastatic HER2-positive ovarian cancer in mice, extending survival independently of tumor antigenicity. Most importantly, HERV synergizes with standard-of-care chemotherapy against ovarian cancer metastases in vivo, with 43% of combination-treated subjects surviving for months beyond subjects treated with either therapy alone. Taken together, these results introduce rewiring of cancer-driving signaling pathways to virotherapeutic activation as a strategy for more specific and effective cancer treatment.

Psilocin is a well-studied controlled substance with potential psychotherapeutic applications. However, research gaps remain regarding its metabolism. Our objective was to elucidate a comprehensive Phase I metabolic profile of psilocin to support its forensic management and clinical development. We utilized human enzymes from various sources to characterize the Phase I metabolism of psilocin and estimated its hepatic and extrahepatic clearances via in vitro to in vivo extrapolation. We identified 2-(4-hydroxy-1H-indol-3-yl)-acetaldehyde (4-HIA) as the Phase I intermediate metabolite for the first time. Psilocin was metabolized to 4-HIA by monoamine oxidase A (MAO-A), and further metabolized to the terminal metabolite 2-(4-hydroxy-1H-indol-3-yl)-acetic acid (4-HIAA) by cytosolic aldehyde oxidase (AO) and aldehyde dehydrogenases (ALDHs). MAO-A-mediated hepatic clearance of psilocin (CL H,MAO-A ) was estimated to be 158.74 mL/min, accounting for 80.9% of the total hepatic metabolism of psilocin (CL H,all ). MAO-A primarily contributed to the Phase I metabolism of psilocin. Total MAO-A-mediated organ clearance (CL all organs,MAO-A ) was estimated to be 614.81 mL/min, with CL H,MAO-A accounting for 25.8%, indicating extensive MAO-A-mediated extrahepatic clearance of psilocin. Overall, our study sheds novel insights on Phase I metabolic pathway of psilocin and illuminated the importance of MAO-A-mediated hepatic and extrahepatic clearances of psilocin., Competing Interests: Declarations. Conflict of interest: The authors have declared that no competing interest exists., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nusinersen and risdiplam are U.S. Food and Drug Administration (FDA)-approved treatments for spinal muscular atrophy (SMA). No head-to-head clinical trials to assess efficacy exist. Observational studies are needed to determine if transitioning to risdiplam is safe and efficacious., Methods: This retrospective study at Nationwide Children's Hospital included individuals with SMA treated with nusinersen who switched to risdiplam. Motor, pulmonary and bulbar function were assessed before and 2 years after nusinersen and risdiplam initiation., Results: Forty-four individuals were included: 11 with SMA type 1, 25 with SMA type 2 and 8 with SMA type 3. Motor function improved after initiation of nusinersen treatment with the most significant improvements seen in the first year. After transition to risdiplam, motor function remained largely stable. Need for noninvasive ventilation (NIV) overnight occurred in both groups. Cough peak flow significantly improved in the risdiplam group. Hospitalizations were the same in both groups. One individual in the nusinersen group gained the ability to take some food by mouth; two individuals in the risdiplam group achieved some oral feeding and two became exclusively orally fed., Conclusions: As expected, motor function was most improved in treatment naïve individuals in the first year after nusinersen initiation. Over half of our study population had posterior spinal fusion surgery (57%) which significantly impacted motor and respiratory outcomes, though slightly less so in the risdiplam group. Overall, our data demonstrates that transitioning from nusinersen to risdiplam is associated with a favorable safety profile and stable motor outcomes., (© 2025 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

The fisheries and aquaculture industry are known for generating substantial waste or by-products, often underutilized, or relegated to low-value purposes. However, this overlooked segment harbors a rich repository of valuable bioactive materials of which have a broad-spectrum of high-value applications. As the blue economy gains momentum and fisheries expand, sustainable exploitation of these aquatic resources is increasingly prioritized. In this review, we present a comprehensive overview of technology-enabled methods for extracting and transforming aquatic waste into valuable biomaterials and their recent advances in regenerative medicine applications, focusing on marine collagen, chitin/chitosan, calcium phosphate and bioactive-peptides. We discuss the inherent bioactive qualities of these "waste-to-resource" aquatic biomaterials and identify opportunities for their use in regenerative medicine to advance healthcare while achieving the Sustainable Development Goals., 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 B.V.)

The objective of this study was to evaluate whether supplementation with probiotics over a 2-week period stabilizes the gut microbiota in dogs following prolonged cefovecin treatment. A significant number of clinical veterinarians prescribe oral probiotics to dogs in conjunction with systemic antibiotics with the intention of protecting against gut dysbiosis. The effects of antibiotics and probiotics in dogs have not been extensively studied, however, and the optimal treatment for gut dysbiosis remains uncertain. To investigate the impact of cefovecin and probiotics on the gut microbiota, 12 healthy companion dogs that underwent surgical castration were included in the study. The dogs were administered cefovecin immediately after surgery. Of the 12 dogs, 7 dogs were supplemented with oral probiotics for 2 wk after cefovecin treatment (probiotic group), whereas the other 5 dogs were not supplemented with probiotics (non-probiotic group). Fecal samples were collected from each dog before and 2 wk after cefovecin treatment and subjected to 16S rRNA gene sequencing using the Illumina platform. We noted that cefovecin induced changes in bacterial diversity of the gut microbiota, with the Shannon index values of the non-probiotic group decreasing significantly, whereas those of the probiotic group remained stable ( P = 0.025). Our findings suggest that supplementation with oral probiotics is recommended for preventing cefovecin-induced gut dysbiosis in dogs., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Parthenocarpy, characterized by seedless fruit development without pollination or fertilization, offers the advantage of consistent fruit formation, even under challenging conditions such as high temperatures. It can be induced by regulating auxin homeostasis; PAD1 ( PARENTAL ADVICE-1 ) is an inducer of parthenocarpy in Solanaceae plants. However, precise editing of PAD1 is not well studied in peppers. Here, we report a highly efficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein (RNP) for CaPAD1 editing in three valuable cultivars of pepper ( Capsicum annuum L.): Dempsey, a gene-editable bell pepper; C15, a transformable commercial inbred line; and Younggo 4, a Korean landrace. To achieve the seedless pepper trait under high temperatures caused by unstable climate change, we designed five single guide RNAs (sgRNAs) targeting the CaPAD1 gene. We evaluated the in vitro on-target activity of the RNP complexes in three cultivars. Subsequently, we introduced five CRISPR/Cas9-RNP complexes into protoplasts isolated from three pepper leaves and compared indel frequencies and patterns through targeted deep sequencing analyses. We selected two sgRNAs, sgRNA2 and sgRNA5, which had high in vivo target efficiencies for the CaPAD1 gene across the three cultivars and were validated as potential off-targets in their genomes. These findings are expected to be valuable tools for developing new seedless pepper cultivars through precise molecular breeding of recalcitrant crops in response to climate change.

There is a lack of an effective prognostic model for predicting outcomes in patients with primary pulmonary hypertension (PPH). A retrospective analysis was conducted on PPH patients from MIMIC and eICU databases. A predictive model was developed to assess mortality risk. The Consistency Index (C-index) and Receiver Operating Characteristic (ROC) curve were utilized to assess the overall performance of the model and its discriminatory capacity. The model's calibration and clinical applicability were assessed through calibration curve and decision curve analysis (DCA). The nomogram was employed for visual representation of the model. The study included 420 patients, 260 in the development group, 104 in the internal validation group and 56 in the external validation group. The predictive model's risk factors included age, respiratory rate, red blood cell distribution width, glucose, and SAPS II. The model demonstrated C-indexes of 0.736 and 0.696 in the development and internal validation groups, respectively. The ROC curves for the development, internal validation and external validation groups demonstrated robust discriminatory capabilities. The calibration curves indicated a slope close to 1, suggesting good calibration of the model. Additionally, DCA analysis revealed the model offered significant clinical benefits across a wide range of thresholds. The model showed good discrimination ability, accuracy and clinical application value in predicting the prognosis of patients with PPH., Competing Interests: Declarations. Ethics approval and consent to participate: The present study had been approved by Ethics Review Committee of the First Affiliated Hospital of Guangxi Medical University (approval number: 2024-E303-01). The studies involving human participants were reviewed and approved by the institutional review boards of the MIT (Cambridge, MA, United States) and BIDMC (Boston, MA, United States). The institutional review boards of the MIT (Cambridge, Massachusetts) and BIDMC (Boston, Massachusetts) reviewed and approved studies involving human participants. Due to the retrospective nature of the study, the Institutional Review Boards of the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center waived the need for obtaining informed consent. According to national laws and institutional requirements, this study does not require written informed consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues. By focusing on these unique functionalities, this review highlights the potential of HA-based systems to revolutionize ocular treatment. Various fabrication techniques for HA-based ocular drug delivery systems, including hydrogels, nanoparticles, and microneedles, are discussed, highlighting their respective advantages and limitations. Additionally, this review explores the clinical applications of HA-based devices in treating a range of ocular diseases, such as dry eye syndrome, glaucoma, retinal disorders, and ocular infections. By comparing the efficacy and safety profiles of these devices with traditional ocular drug delivery methods, this review aims to provide a comprehensive understanding of the potential benefits and challenges associated with HA-based systems. Moreover, this review discusses current limitations and future directions in the field, such as the need for standardized fabrication protocols, long-term biocompatibility studies, and large-scale clinical trials. The insights and advancements presented in this review aim to guide future research and development efforts, ultimately enhancing the effectiveness of ocular drug delivery and improving patient outcomes.

To analyze the source apportionment, potential ecological risk, and health risk of heavy metals in soils surrounding a manganese tailings pond in Chongqing, a positive matrix factorization （PMF） model, potential ecological risk index, and health risk assessment model were used. Further, all three models were combined to explore the risks of heavy metals in soils by different pollution sources to determine the priority control factors. The results showed that except for the Cr concentration, the average values of Mn, Cd, As, Pb, Cu, Zn, and Ni concentration were higher than their corresponding background values. Using the PMF model analysis, mining, natural, agricultural, and industrial sources were identified as the determinants for the accumulation of heavy metals in soils, with contribution rates of 23.9%, 30.2%, 18.8%, and 27.1%, respectively. Using potential ecological risk index analysis, the ecological risk was predominantly categorized as "strong" risk, with the rate of 77.8%. The health risk assessment model analysis revealed that, the carcinogenic risks of adults and children were tolerable, whereas the non-carcinogenic risks were acceptable. According to the analysis results of the relationship among heavy metals, pollution sources, potential ecological risk, and health risks showed that agricultural sources were identified as the priority control sources, with Cd as the primary control factor. Mining sources and industrial sources were identified as secondary control sources, with Mn and As as the secondary control factors.

PM 2.5 is an important indicator for measuring the degree of air pollution. Studying the space-time variation and the driving factors of spatial heterogeneity is important for controlling air pollution and improving regional air quality. Based on PM 2.5 remote sensing data from 2000 to 2021, the Theil-Sen Median trend analysis, Mann-Kendall significant inspection, and spatial auto correlation were used to analyze the characteristics of space-time changes in PM 2.5 concentration, and geographical detectors were combined with a multi-scale geographical weighted regression model to explore the key driver factor and its influence and direction of the impact and role of PM 2.5 spatial differences. The results showed that： ① The average PM 2.5 value of Heilongjiang Province was between 22.01 and 41 μg·m -3 from 2000 to 2021. From 2008 to 2015, the average PM 2.5 value was higher than the secondary concentration limit （35 μg·m -3 ） of the "Environmental Air Quality Standard." The turning point of the PM 2.5 concentration change that occurred in 2013 generally showed the trend of change and then a downward trend. Winter was the high incidence season for PM 2.5 pollution. The PM 2.5 concentration space was a distributed pattern in the south and north and the high-value zone was mainly based on Harbin, Daqing City, and the surrounding area. The low-value areas were distributed in the northern regions such as the Great Khingan Mountains Region and Heihe City. ② Factor detection results indicated that the average annual temperature was the most important driving factor that affected PM 2.5 spatial differences. The remaining key driver factors were in turn： high-end, population density, average annual wind speed, land use, night lights, annual years precipitation, slope, annual relative humidity, and NDVI. Interactive detection showed that the interpretation of PM 2.5 points after interaction was higher than a single factor after interaction, indicating that affecting PM 2.5 spatial difference was the result of the common effect of each driver factor. The effect of natural factors was more obvious than that of social and economic factors. ③ The effect of different influence factors on PM 2.5 had a significant spatial difference. The average annual temperature, average annual relative humidity, population density, and night lighting played a promotion effect on PM 2.5 pollution and NDVI and land use played an inhibitory effect on PM 2.5 pollution. PM 2.5 was significantly different from the action role of various influencing factors and the average annual temperature, annual average wind speed, and NDVI impact scale were the smallest, with a variable bandwidth of 43； population density and land use impact scale were the largest, with a variable bandwidth of 140.

Citrus yellow vein-clearing virus (Potexvirus citriflavivenae; CYVCV) is an increasing threat to citrus cultivation. Notably, the role of zinc finger proteins (ZFPs) in mediating viral resistance in citrus plants is unclear. In this study, we demonstrated that ZFPs ClSUP and ClDOF3.4 enhanced citrus defense responses against CYVCV in Eureka lemon (Citrus limon 'Eureka'). ClSUP interacted with the coat protein (CP) of CYVCV to reduce CP accumulation and inhibited its silencing suppressor function. Overexpression of CISUP triggered reactive oxygen species (ROS) and salicylic acid (SA) pathways, and enhanced resistance to CYVCV infection. In contrast, ClSUP silencing resulted in increased CP accumulation and down-regulated ROS and SA-related genes. ClDOF3.4 interacted with ClSUP to facilitate its interactions with CP. Furthermore, ClDOF3.4 synergistically regulated the accumulation of ROS and SA with ClSUP and accelerated down-regulation of CP accumulation. Transgenic plants co-expressing ClSUP and ClDOF3.4 significantly decreased the CYVCV. These findings provide a new reference for understanding the interaction mechanism between the host and CYVCV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To investigate the toxicity of terpinen-4-ol (T4O) on primary cultured human corneal epithelial cells (HCECs)., Methods: HCECs were exposed to various concentrations (0%-0.1%) of T4O for 15 minutes to 72 hours. Cell viability was assessed using the CCK8 kit and cell counting. Intracellular reactive oxygen species (ROS) were measured after 15 to 60 minutes of T4O exposure. Changes in cell morphology and cytoplasmic actin filaments were observed using phase contrast microscopy and immunocytochemistry. The expression levels of proteins involved in cell survival pathways (mTOR, Akt, Bcl-xL, and BAX) were evaluated by Western blot analysis., Results: T4O induced dose-dependent toxicity in HCECs. Exposure to 0.05% T4O for 15 minutes significantly decreased cell viability. Lower concentrations (0.025% and 0.0125%) also caused significant toxicity with longer exposure times. Prolonged exposure enhanced cytotoxicity, with 0.05% T4O reducing viability by half after 24 hours and 0.1% T4O causing complete cell death. Increased intracellular ROS and decreased levels of phosphorylated mTOR, phosphorylated Akt, and Bcl-xL, along with increased BAX expression, accompanied this toxicity. F-actin staining revealed significant changes in cell adhesion., Conclusions: Our study demonstrates that T4O exposure causes significant toxicity in HCECs, depending on concentration and incubation time. This toxic response is associated with increased ROS and decreased cell survival pathway activity., Translational Relevance: The corneal epithelial toxicity data of T4O revealed in this study may be useful in the future use of tea tree oil or the development of tee tree oil-containing eyelid scrub products for treating eyelid demodex infestation.

Objectives: To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC)., Materials and Methods: The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders., Results: Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008)., Conclusion: In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB., (© 2024 ARS‐AAOA, LLC.)

The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy., (© 2024 Wiley‐VCH GmbH.)

The massive proliferation of Microcystis threatens freshwater ecosystems and degrades water quality globally. Understanding the mechanisms that contribute to Microcystis growth is crucial for managing Microcystis blooms. The lifestyles of bacteria can be classified generally into two groups: particle-attached (PA; > 3 µm) and free-living (FL; 0.2-3.0 µm). However, little is known about the response of PA and FL bacteria to Microcystis blooms. Using 16S rRNA gene high-throughput sequencing, we investigated the stability, assembly process, and co-occurrence patterns of PA and FL bacterial communities during distinct bloom stages. PA bacteria were phylogenetically different from their FL counterparts. Microcystis blooms substantially influenced bacterial communities. The time decay relationship model revealed that Microcystis blooms might increase the stability of both PA and FL bacterial communities. A contrasting community assembly mechanism was observed between the PA and FL bacterial communities. Throughout Microcystis blooms, homogeneous selection was the major assembly process that impacted the PA bacterial community, whereas drift explained much of the turnover of the FL bacterial community. Both PA and FL bacterial communities could be separated into modules related to different phases of Microcystis blooms. Microcystis blooms altered the assembly process of PA and FL bacterial communities. PA bacterial community appeared to be more responsive to Microcystis blooms than FL bacteria. Decomposition of Microcystis blooms may enhance cooperation among bacteria. Our findings highlight the importance of studying bacterial lifestyles to understand their functions in regulating Microcystis blooms. KEY POINTS: • Microcystis blooms alter the assembly process of PA and FL bacterial communities • Microcystis blooms increase the stability of both PA and FL bacterial communities • PA bacteria seem to be more responsive to Microcystis blooms than FL bacteria., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The global production of radioactive wastes is expected to increase in the coming years as more countries have resorted to adopting nuclear power to decrease their reliance on fossil-fuel-generated energy. Discoveries of remediation methods that can remove radionuclides from radioactive wastes, including those discharged to the environment, are therefore vital to reduce risks-upon-exposure radionuclides posed to humans and wildlife. Among various remediation approaches available, microbe-mediated radionuclide remediation have limited reviews regarding their advances. This review provides an overview of the sources and existing classification of radioactive wastes, followed by a brief introduction to existing radionuclide remediation (physical, chemical, and electrochemical) approaches. Microbe-mediated radionuclide remediation (bacterial, myco-, and phycoremediation) is then extensively discussed. Bacterial remediation involves biological processes like bioreduction, biosorption, and bioprecipitation. Bioreduction involves the reduction of water-soluble, mobile radionuclides to water-insoluble, immobile lower oxidation states by ferric iron-reducing, sulfate-reducing, and certain extremophilic bacteria, and in situ remediation has become possible by adding electron donors to contaminated waters to enrich indigenous iron- and sulfate-reducing bacteria populations. In biosorption, radionuclides are associated with functional groups on the microbial cell surface, followed by getting reduced to immobilized forms or precipitated intracellularly or extracellularly. Myco- and phycoremediation often involve processes like biosorption and bioaccumulation, where the former is influenced by pH and cell concentration. A Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis on microbial remediation is also performed. It is suggested that two research directions: genetic engineering of radiation-resistant microorganisms and co-application of microbe-mediated remediation with other remediation methods could potentially result in the discovery of in situ or ex situ microbe-involving radioactive waste remediation applications with high practicability. Finally, a comparison between the strengths and weaknesses of each approach is provided., 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.)

Introduction: A digital twin is a virtual representation of the real world. This paper presents the concept of a digital twin system that reflects the movements of the human skeleton as the body is repositioned. Digital twin technology has the ability to be used as a training tool for new radiographers to build their competencies due to its ability to provide visual feedback without the use of radiation. This study aims to evaluate the perceptions of radiography trainers and trainees regarding the utility of digital twin technology., Methods: The concept of digital twin technology was demonstrated to 46 trainers and trainees. Surveys were distributed online on the same day as the demonstration to gather feedback from the participants regarding the perceived usefulness of digital twin technology. For dichotomized and categorical variables, the relationships among these variables were examined using either the chi-squared test or Fisher's exact test. Inductive thematic analysis was used to analyze the open-ended questions., Results: Most respondents were willing to use digital twin technology (91.1 %) and agreed that it would be useful for education and training purposes (95.5 %). They also felt that it would improve radiographic skills (84.4 %) and confidence (93.3 %). Concerns regarding the product included its sensitivity to capturing subtle changes in positioning and its user-friendliness in terms of customization, and potential dependence on technology when positioning patients., Conclusion: Digital twin technology has the potential to be a valuable training tool by allowing radiographers to hone their radiographic skills in a safe environment without the need for radiation exposure., (Copyright © 2024. Published by Elsevier Inc.)

Inhibiting cyclin-dependent kinases (CDK) offers an important arsenal for cancer treatments by interfering with apoptotic proteins related to cancer. Novel selective cyclin-dependent kinases inhibitors using the Quinazoline as the cap with multiple electronic donating (EDG) and/or electron withdrawing group (EWG) substituted Aniline chain at the C-2 position were designed, synthesized, and evaluated for activity against liver cancer. Among the tested compounds, compounds B34 and B35 emerged as potent candidates in the series, with IC 50 values of 0.102 ± 0.04 µM and 0.058 ± 0.003 µM, respectively. They also suppressed the enzymatic activity of CDK2/cyclinA2 selectively. Further biological studies revealed that compounds B34 and B35 arrested the cell cycle, and induced apoptosis in HepG-2 cancer cells through a Caspase-mediated mechanism, facilitating the release of Cyt-c through modulation of Caspase-3 expression. More importantly, compounds B34 and B35 suppressed the xenografted tumor growth in mice in a dose-dependent manner. Finally, through a molecular docking study, it was confirmed that compoundsB34 andB35 retained crucial hydrogen bonding and hydrophobic interactions with CDK receptor, rationalizing their higher efficacy compared to other compounds in the series. Taken together, the Quinazoline derivatives B34 and B35 may serve as novel chemotherapeutic agents through inhibition of CDK., 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.)

Performance of the group IV monochalcogenide GeSe in solar cells, electronic, and optoelectronic devices is expected to improve when high-quality single crystalline material is used rather than polycrystalline films. Crystalline flakes represent an attractive alternative to bulk single crystals as their synthesis may be developed to be scalable, faster, and with higher overall yield. However, large - and especially large and thin - single crystal flakes are notoriously hard to synthesize. Here it is demonstrated that vapor-liquid-solid growth combined with direct lateral vapor-solid incorporation produces high-quality single crystalline GeSe ribbons with tens of micrometers size and controllable thickness. Electron microscopy shows that the ribbons exhibit perfect equilibrium (AB) van der Waals stacking order without extended defects across the entire thickness, in contrast to the conventional case of substrate-supported flakes where material is added via layer-by-layer nucleation and growth on the basal plane. Electrical measurements show anisotropic transport and a high Hall mobility of 85 cm 2  V -1  s -1 , on par with the best single crystals to date. Growth from mixed GeSe and SnSe vapors, finally, yields ribbons with unchanged structure and composition but with jagged edges, promising for applications that rely on ample chemically active edge sites, such as catalysis or photocatalysis., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Leukemia stem cells (LSCs) are widely believed to reside in well-characterized bone marrow (BM) niches; however, the capacity of the BM niches to accommodate LSCs is insufficient, and a significant proportion of LSCs are instead maintained in regions outside the BM. The molecular basis for this niche-independent behavior of LSCs remains elusive. Here, we show that integrin-α9 overexpression (ITGA9 OE) plays a pivotal role in the extramedullary maintenance of LSCs by molecularly mimicking the niche-interacting status, through the binding with its soluble ligand, osteopontin (OPN). Retroviral insertional mutagenesis conducted on leukemia-prone Runx-deficient mice identified Itga9 OE as a novel leukemogenic event. Itga9 OE activates Akt and p38MAPK signaling pathways. The elevated Myc expression subsequently enhances ribosomal biogenesis to overcome the cell integrity defect caused by the preexisting Runx alteration. The Itga9-Myc axis, originally discovered in mice, was further confirmed in multiple human acute myeloid leukemia (AML) subtypes, other than RUNX leukemias. In addition, ITGA9 was shown to be a functional LSC marker of the best prognostic value among 14 known LSC markers tested. Notably, the binding of ITGA9 with soluble OPN, a known negative regulator against HSC activation, induced LSC dormancy, while the disruption of ITGA9-soluble OPN interaction caused rapid cell propagation. These findings suggest that the ITGA9 OE increases both actively proliferating leukemia cells and dormant LSCs in a well-balanced manner, thereby maintaining LSCs. The ITGA9 OE would serve as a novel therapeutic target in AML., 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.)

A novel Gram-negative bacterial strain, 20NA77.7 T , was isolated from fresh water of the Nakdong River. Strain 20NA77.7 T shared the highest similarity with Flavobacterium indicum GPTSA100-9 T (97.91%) and Flavobacterium urocaniciphilum DSM 27078 T (96.24%) in the 16S rRNA gene sequence. The digital DNA-DNA hybridization and average nucleotide identity values for strain 20NA77.7 T with Flavobacterium species were below 20.8% and 77.33%, respectively. The major fatty acids of strain 20NA77.7 T were identified as iso-C 15:0 , iso-C 16:0 , iso-C 15:1 G, anteiso-C 15:0 , iso-C 15:0 3OH, and iso-C 16:0 3OH. Strain 20NA77.7 T contained phosphatidylethanolamine, one unidentified aminolipid, and three unidentified lipids as polar lipids and menaquinone-6 as menaquinone. The polyphasic evidence supports the classification of strain 20NA77.7 T as a novel species belonging to the genus Flavobacterium , for which the name Flavobacterium nakdongensis is proposed. The type strain is 20NA77.7 T (= KCTC 102000 T = LMG 33137 T ).

The precise asymmetric photochemical transformation of organic compounds containing multiple reactive sites presents significant progress in synthetic chemistry. Herein, we report an unprecedented visible-light-induced cascade transformation of tropolone cyclic triene derivatives by using chiral photoactive metal-organic cages (cPMOCs) as enzyme-mimicking multipocket photocatalysts. The cage-confined photocatalysis promotes three successive elementary steps, i.e ., enantioselective [2 + 2] photocycloaddition with chalcone, regio-, and diastereoselective α-ketol rearrangement, and a stereoselective 1,3-acyl shift, resulting in bicyclo[3.2.2]nonane skeleton with multichiral-centers unattainable by other methods. This study demonstrates how complex synthetic challenges of peri-, chemo-, and stereoselectivities could be subtly manipulated by cage-confined supramolecular catalysis for exploration of new reactivities.

Background: Primary hepatic leiomyosarcoma (PHL) is a rare malignant tumor and has non-specific clinical manifestations and imaging characteristics, making preoperative diagnosis challenging. Here, we report a case of PHL presenting primarily with fever, with computed tomography imaging showing a thick-walled hepatic lesion with low-density areas, resembling liver abscess., Case Summary: The patient was a 34-year-old woman who presented with right upper abdominal pain and fever over 4 days before admission. Based on the patient's medical history, laboratory examinations, and imaging examinations, liver abscess was suspected. Mesenchymal tumor was diagnosed by percutaneous liverbiopsy and partial hepatectomy was performed. Postoperative pathology revealed PHL. The patient is currently undergoing intravenous chemotherapy with the AD regimen and shows no signs of recurrence., Conclusion: When there is a thick wall and rich blood supply in the hepatic lesion with a large proportion of uneven low-density areas, PHL should be considered., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A novel rod-shaped, Gram-stain-negative bacterial strain MS17 T was obtained from a co-culture of Microcystis aeruginosa and Myriophyllum spicatum. The examination of the 16S ribosomal RNA gene sequence showed a significant degree of similarity between strain MS17 T and Paucibacter sediminis S2-9 T (98.4%), Roseateles violae PFR6 T (98.1%), 'Roseateles cellulosilyticus' P8 T (98.0%), Roseateles aquae APW11 T (97.9%), Roseateles oligotrophus CHU3 T (97.7%), Roseateles saccharophilus DSM 654 T (97.6%), Kinneretia aquatilis CR182 T (97.7%), Pelomonas aquatica CCUG 52575 T (97.6%), and Roseateles toxinivorans 2C20 T (97.0%). Between strain MS17 T and the type strains of closely related species, digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were below 21.9% and 78.48%. The respiratory quinone was ubiquinone Q-8. The main fatty acids (> 10.0%) were C 15:1 ω6c, C 16:0 , C 17:0 , and summed feature 3 (C 16:1 ω7c and/or C 16:1 ω6c). The polar lipids comprised phosphatidylethanolamine, unidentified phospholipid, phosphatidylglycerol, unidentified aminophospholipid, unidentified aminolipid, and three unidentified lipids. The genomic G + C content was 65.9%. According to phenotypic characteristics, phylogenetic relationships, and chemotaxonomic data, strain MS17 T has been categorized as a newly discovered species belonging to the Roseateles genus, and the name Roseateles microcysteis sp. nov. is suggested. It exhibits distinct biochemical properties that differentiate it from closely related species. The type strain is MS17 T (=KCTC 8001 T  = LMG 33142 T )., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To observe the effect of electroacupuncture (EA) on sleep quality and electroencephalogram (EEG) signal in the patients with chronic insomnia and to explore its mechanism., Methods: Sixty patients with chronic insomnia were randomized into an EA group (30 cases, 3 cases dropped out) and a health learning group (30 cases, 3 cases dropped out). In the health learning group, the sleep health education was provided. In the EA group, besides the health education as the health learning group, EA was delivered at Baihui (GV20), Yintang (GV24 + ), bilateral Shenmen (HT7), bilateral Sanyinjiao (SP6), with continuous wave, 2 Hz in frequency, once every other day, and 3 interventions a week. EA was given for 4 weeks successi-vely, composed of 12 treatments. The score of Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), and patient health questionnaire-9 (PHQ-9) before and after treatment were compared between the two groups. The EEG signals were collected and the relative power and entropy of EEG before and after treatment were compared between the two groups., Results: After treatment, the scores of PSQI, HAMA and PHQ-9, the relevant power of β wave in F8 and T3 channels, and that of α wave in T4 channel, and the entropy in T3 channel under the eyes-open (EO) resting state, as well as the relevant power and the entropy of γ wave in F8 channel under the eyes-closed (EC) resting state in the EA group were lower ( P <0.05) than those before the treatment. All of the above results were lower than those of the health learning group at the same time points ( P <0.05). Under the EO resting state, the relevant power of the θ and δ waves of T3 channel and θ wave of T4, O2 and Pz channels of patients in the EA group after the treatment were increased ( P <0.05) than those before the treatment, and higher ( P <0.05) than those of the health learning group at the same time points., Conclusions: Acupuncture is effective on chronic insomnia, which may be related to the regulation EEG signals.

Inflammatory bowel disease (IBD) has the potential to induce neuroinflammation, which may increase the risk of developing neurodegenerative disorders. Ultrasound stimulation to the abdomen is a potential treatment for dextran sulfate sodium (DSS)-induced acute colitis. The present study aimed to investigate whether abdominal low-intensity pulsed ultrasound (LIPUS) can alleviate DSS-induced neuroinflammation through the microbiota-gut-brain axis. Male mice were fed DSS to induce ulcerative colitis. LIPUS stimulation was then applied to the abdomen at intensities of 0.5 and 1.0 ​W/cm 2 . Mouse biological samples were analyzed, and behavior was evaluated. [ 18 F]FEPPA PET/CT imaging was employed to track and quantify inflammation in the abdomen and brain. Changes in the gut microbiota composition were analyzed using 16S rRNA sequencing. Abdominal LIPUS significantly inhibited the DSS-induced inflammatory response, repaired destroyed crypts, and partially preserved the epithelial barrier. [ 18 F]FEPPA accumulation in the colitis-induced neuroinflammation in the abdomen and specific brain regions significantly decreased after LIPUS treatment. LIPUS maintained intestinal integrity by increasing zonula occludens and occludin levels, reduced lipopolysaccharide-binding protein and lipopolysaccharide levels in the serum, and improved behavioral dysfunctions. Moreover, LIPUS, at an intensity of 0.5 ​W/cm 2 , reshaped the gut microbiota in colitis-induced mice by increasing the relative abundance of the Firmicutes and decreasing the relative abundance of the Bacteroidota. Our findings demonstrated that abdominal LIPUS stimulation has the potential to be a novel therapeutic strategy to improve colitis-induced behavioral disorders through microbiota-gut-brain axis signaling., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

The choice of trap in entomological surveys affects the composition of captured insects, though previous comparative studies have been limited in the types of composition measured, and the effects of environmental context. We assessed the sampling bias of several traps commonly used in pollinator monitoring: blue, yellow, and white pan traps, and blue vane traps, towards different taxonomic and functional groups and their efficiency in measuring taxonomic, phylogenetic, and functional diversity. Analyses were performed in monoculture and mixed forests to understand the environmental context of trap efficiency. We found that blue pan traps generally outperformed other types in bee capture and exhibited a preference for Halictidae bees. Blue pan traps yielded the highest species richness and phylogenetic diversity, while blue vane traps captured the highest functional richness. Bias differences were frequently detected in mixed forests compared with monoculture forests. We also found the combination of blue vane and pan traps consistently correlated highest with a complete survey among two-method combinations. Based on our findings, we recommend a combination of blue vane and pan traps to obtain a more comprehensive bee collection in an efficient manner. Additionally, it is crucial to consider habitat type when designing bee trapping protocols to ensure an accurate representation of bee communities.

Axially chiral tetrasubstituted alkenes are of increasing value and interest in chemistry-related areas. However, their catalytic asymmetric synthesis remains elusive, owing to the high steric repulsion and relatively low conformational stability. Herein, we disclose the straightforward construction of atropisomeric tetrasubstituted alkenes by effective enantiocontrol in a reaction with vinyl cation intermediates. This copper-catalyzed enantioselective C(sp 2 )-H functionalization of sterically hindered (hetero)arenes with vinyl cations enables the efficient and atom-economical preparation of axially chiral acyclic tetrasubstituted styrenes and pyrrolyl ethylenes with high atroposelectivities. Importantly, this reaction represents the first example of the assembly of axially chiral alkenes via vinyl cations. Computational mechanistic studies reveal the reaction mechanism, origin of regioselectivity, Z/E selectivity and enantioselectivity. The synthetic utility has been demonstrated by diverse product derivatizations, chiral organocatalyst synthesis, as well as further applications in asymmetric catalysis., (© 2024 Wiley-VCH GmbH.)

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl 4 )-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl 4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration., 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.)

ConspectusThe emulation of ingenious biofunctions has been a research focus for several decades. Metal-organic cages (MOCs), as a type of discrete supramolecular assembly with well-defined shapes and cavities, have aroused great interest in chemists to imitate natural protein cages or enzymes. However, to genuinely achieve tailored functionalities or reactivities of enzymes, the design of cage structures combining both the confined microenvironment and the active site is a prerequisite. Therefore, the integration of functionalized motifs into MOCs is expected to provide a feasible approach to construct biofunctional confined nanospaces, which not only allows the modulation of cage properties for applications such as molecular recognition, transport, and catalysis but also creates unique microenvironments that promote enzymatic effects for special reactivities and selectivities, thereby providing a versatile platform to achieve exceptional biomimetic functions and beyond.In this Account, we specifically focus on our research toward engineering active confined-nanospaces in MOCs via incorporation of M(ImPhen) 3 metalloligands, a typical tris-chelate coordination moiety comprising imidazophenanthroline ligands and variable metal ions, as the principle functional units for stepwise assembly of active-MOCs. Starting from their structure design and merits, we describe the versatility of M(ImPhen) 3 centers for multifunctionalization of the confined cage-nanospaces. By integrating different metal ions like Ru, Os, Fe, Co, Ni, Zn, the metal ion inherent properties, e.g., redox activity of Fe/Co-centers, chirality, and photoactivity of Ru-centers, and dynamics of Co/Zn-centers, could be integrated and tailored on the cages as isostructural nanosized containers or reactors. Changing the Pd or Pt cage vertices to organic clips could remarkably enhance acid-base stability and endow cages with flexibility and allostery. Utilization of ImPhen organic ligands containing imidazole groups introduces proton transfer capability, which can couple with the high-positive charges on the cage to create amphoteric microenvironments in the porous open-cage solution. Moreover, the nonplanar stereoconfiguration of M(ImPhen) 3 confers multiple peripheral pockets on the cage, which render multisite, high-order, and dynamics guest binding for the benefit of applications such as drug delivery, molecular separation, and catalytic turnover.The construction of active-MOCs from tailorable M(ImPhen) 3 metalloligands provides us with a new perspective on their structural design and functionalities. Merging the cage confinement with distinct physicochemical properties on a supramolecular level makes it practical to realize synergistic and cooperative effects for functionality enhancement beyond molecular components or the reactivity different from the bulky solution, which could largely expand the potential of MOCs as a multirole platform to wide application scenarios such as artificial photosynthesis, unconventional catalysis, and theranostic nanomedicine.

Diabetes mellitus (DM) is a group of diseases characterized by high blood glucose caused by insufficient absolute or relative secretion of insulin. Once diagnosed, patients need long-term treatment with hypoglycemic drugs. Currently, the existing first-line hypoglycemic drugs do not provide effective treatment for DM and its complications. In the past, the first generation and the second generation of weight loss surgery, such as gastric bypass and sleeve gastric surgery, had strict body mass index requirements. Moreover, post-surgery, patients are prone to fluctuating hypoglycemia, gastroesophageal reflux, and dumping syndrome. Hence, the curative effect of this type of surgery was compromised to a certain extent. Jejunoileostomy is a third-generation surgery for patients with DM, which has been shown to improve glucose and lipid metabolism, without changing the original gastrointestinal tract structure. Different from previous weight loss surgeries, jejunoileostomy has been clinically observed to delay the development of DM-related complications. Additionally, the postoperative complications are mild and do not affect the patient's quality of life. Based on our clinical observations from multi-center large samples, our team developed a consensus on the operative period and perioperative management of jejunoileostomy as a reference for clinical researchers., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Trichoderma sp . AH pretreatment (PT) enhances the conversion and selectivity of RS and WS in supercritical methanolysis. In this work, we investigated how Trichoderma sp . AH-containing PT affected the structure of wheat straw (WS) and rice straw (RS). The enhanced straw supercritical methanolysis was mostly ascribed to structural changes in RS and WS during PT based on thorough investigations by thermogravimetry/differential thermogravimetry (TG/DTG), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The TG/DTG study revealed that PT could only partially degrade RS and WS without significantly changing the makeup of their group. PT is effective at breaking the structure because XRD research showed that it could only somewhat alter the crystal structure of RS and WS, decreasing their crystallinity. The primary way that PT affects RS and WS is by the decrystallization of cellulose and hemicelluloses into an amorphous material. The comparative concentrations of certain molecules are altered by PT, according to XPS examination of these compounds. PT is an efficient biomass liquefaction preparation that minimizes carbohydrate loss by disrupting the structure of the biomass., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Phosphaenones, like their carbon analogue enones (C[double bond, length as m-dash]C-C[double bond, length as m-dash]O), are promising building blocks for synthetic chemistry and materials science. However, in contrast to the α- and β-phosphaenones, structurally and spectroscopically well-defined diphosphaenones (DPEs) are rare. In this study, we disclose the isolation and spectroscopic characterization of N-heterocyclic vinyl (NHV) substituted acyclic DPEs 3a,b [NHV-P[double bond, length as m-dash]P-C(O)-NHV]. X-ray diffraction methods allowed determination of the structures, which show a central planar trans P[double bond, length as m-dash]P-C[double bond, length as m-dash]O configuration. Compound 3a behaves like classical enones and shows 1,4-addition across the P[double bond, length as m-dash]P-C[double bond, length as m-dash]O unit, which proceeds in a stepwise manner. In contrast, 3a exhibits also 1,2-addition across the P[double bond, length as m-dash]P but not the C[double bond, length as m-dash]O double bond, which differentiates it from enones., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT)., Materials and Methods: Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival., Results: During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p<0.001), Karnofsky Performance Status ≥60 (p=0.033), and age ≤75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months, p=0.014)., Conclusion: The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

Self-assembling DNA nanoparticles have the potential to significantly advance the targeted delivery of molecular cargo owing to their chemical and architectural flexibility. Recently, it has been demonstrated that the genetic code embedded in DNA nanoparticles produced by the method of DNA origami or related techniques can be recognized and copied by RNA polymerase in vitro. Further, sculpted DNA nanoparticles can serve as a substrate for Cas9-mediated gene modification and gene expression in cell culture. In the present study, we further investigate the ability of DNA origami nanoparticles to be expressed in a human cell line with emphasis on the impact of single-stranded DNA (ssDNA) domains and the contributions of the architectural disposition of genetic control elements, namely promoter and enhancer sequences. Our findings suggest that while cells possess the remarkable capability to express genes within highly folded architectures, the presence and relative density and location of ssDNA domains appears to influence overall levels of gene expression. These results suggest that it may be possible to nuance folded DNA nanoparticle architecture to regulate the rate and/or level of gene expression. Considering the highly malleable architecture and chemistry of self-assembling DNA nanoparticles, these findings motivate further exploration of their potential as an economic nanotechnology platform for targeted gene editing, nucleic acid-based vaccines, and related biotherapeutic applications., (© 2024. The Author(s).)

Formamidinium lead iodide (FAPI) has gained attention for hybrid perovskite solar cell (PSC) applications due to its enhanced stability and narrow bandgap. However, a significant challenge remains in inducing and stabilizing the elusive perovskite "black phase"─photoactive cubic α-FAPI─as the relatively bulky FA + cations tend to favor the thermodynamically stable nonphotoactive "yellow phase". In this study, we present a templated growth strategy employing thiol-functionalized MoS 2 nanosheets as templates. By introduction of 3-mercaptopropionic acid (MPA)-functionalized MoS 2 as a growth template, precise control over crystal formation was achieved, favoring the growth of high-quality α-FAPI films. These advanced templated films exhibited substantial improvements in charge transport properties, efficient light absorption, and enhanced charge extraction. As a result, the PSCs achieved a significantly enhanced power conversion efficiency (PCE) compared to the nontemplated control device, increasing from 20.6 to 22.5%. The MoS 2 -incorporated device also demonstrated excellent shelf stability, maintaining 91% of the initial PCE even after 1600 h of storage without device encapsulation.

The anti-Acanthamoeba properties of riboflavin and its enhanced amoebicidal effects when combined with ultraviolet A (UVA) radiation were investigated in vitro. The viability of cultured Acanthamoeba castellanii was assessed by adding varying concentrations (0 ~ 0.2% w/v) of riboflavin to the culture medium or after combined riboflavin and UVA treatment (30 min, 3 mW/cm 2 ) over 1, 3, 5, and 7 days. Intracellular reactive oxygen species (ROS) levels were measured following a 30-minute exposure to riboflavin. Additionally, the cysticidal effects of riboflavin, UVA, and their combination were evaluated. Gene transcription in Acanthamoeba was analyzed using RNA-seq. Riboflavin demonstrated dose-dependent toxicity on Acanthamoeba, accompanied by an increase in intracellular ROS. Exposure to 0.2% riboflavin reduced Acanthamoeba viability by over 50% within one day. UVA treatment alone also reduced viability by over 50%. Combined treatment with 0.2% riboflavin decreased trophozoite survival by more than 80%, and approximately 60% of cysts were killed when 0.1% riboflavin was combined with UVA. RNA-seq analysis indicated significant changes in gene expression after exposure to riboflavin, UVA, and their combination, particularly affecting oxidoreductase activity, cystathionine β synthase, and serine-threonine kinase activity. These findings indicate that riboflavin exhibits dose-dependent toxicity in Acanthamoeba, primarily through increased ROS generation. Combining riboflavin and UVA did not fully eradicate trophozoites and cysts of Acanthamoeba, but was able to partially inactivate them., (© 2024. The Author(s).)

Dimensionality reduction is a method used in machine learning and data science to reduce the dimensions in a dataset. While linear methods are generally less effective at dimensionality reduction than nonlinear methods, they can provide a linear relationship between the original data and the dimensionality-reduced representation, leading to better interpretability. In this research, we present a tied-weight autoencoder as a dimensionality reduction model with the merit of both linear and nonlinear methods. Although the tied-weight autoencoder is a nonlinear dimensionality reduction model, we approximate it to function as a linear model. This is achieved by removing the hidden layer units that are largely inactivated by the input data, while preserving the model's effectiveness. We evaluate the proposed model by comparing its performance with other linear and nonlinear models using benchmark datasets. Our results show that the proposed model performs comparably to the nonlinear model of a similar autoencoder structure to the proposed model. More importantly, we show that the proposed model outperforms the linear models in various metrics, including the mean square error, data reconstruction, and the classification of low-dimensional projections of the input data. Thus, our study provides general recommendations for best practices in dimensionality reduction., (© 2024. The Author(s).)

Background: Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status., Patients and Methods: We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care., Results: With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, P < .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, P < .001)., Conclusions: The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations., (© The Author(s) 2024. Published by Oxford University Press.)