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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

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).)

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.

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.

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.

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.)

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.)

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 ).

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.)

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.

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).)

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.)

This study analyzed the enhancement effects and mechanisms of steel, glass, and polypropylene fibers on the mechanical properties of concrete, aiming to guide the selection of suitable fiber types and dosages for shotcrete projects. Through laboratory tests, numerical simulations, and field experiments, it investigated the enhancement laws of flexural and compressive strengths of concrete with different dosages of these three fibers. Results showed: (1) After 28 days of curing, flexural strength peaked with 2.0% steel, 1.5% glass, and 2.0% polypropylene fibers, increasing by 118.6%, 42.86%, and 138.6%, respectively, over plain concrete. Compressive strength increased by 2.13%, 10%, and 18.3% at optimal dosages of 0.5%, 1.0%, and 2.0% for steel, glass, and polypropylene fibers. Fiber effects on compressive strength were less significant than on flexural strength, with polypropylene fibers outperforming the others. (2) Based on ABAQUS numerical simulations, microscopic analysis indicates that fibers, due to their high yield capacity, enhance the connections between concrete elements, reduce stress concentration, and improve the mechanical properties of concrete. (3) For shotcrete, 2.0% polypropylene fibers were preferred due to high flexural strength and reduced agglomeration. (4) The optimal dosage was applied to a mine's wet shotcrete support, effectively controlling tunnel deformation. These findings provide practical guidance for shotcrete applications., (© 2024. The Author(s).)

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future., 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 Authors. Published by Elsevier Inc. All rights reserved.)

An 8-year-old spayed female Maltese dog was referred with a 4-month history of multifocal pruritic erosive or ulcerative lesions on the head, ventral neck, chest, and abdomen; and chronic otitis externa. Biopsy revealed cytotoxic dermatitis and apoptotic keratinocytes with occasional lymphocytic satellitosis. Bacterial culture and antimicrobial susceptibility tests revealed multidrug-resistant Pseudomonas aeruginosa infection of the skin and ears. The skin lesions regressed after treatment of P. aeruginosa infection with ciprofloxacin. Based on the skin lesions, histological characteristics, and response to therapy, the dog was presumed to have erythema multiforme induced by P. aeruginosa infection. This case report emphasizes that P. aeruginosa infection could be a trigger of erythema multiforme in dogs. Key clinical message: Erythema multiforme caused by infection is rare and poorly characterized in the veterinary literature. This case report describes the clinical characteristics of, diagnostic approach to, and treatment of erythema multiforme caused by Pseudomonas aeruginosa ., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: The time to surgery (TTS) after the completion of the final cycle of neoadjuvant chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) is inconsistent. Pathological complete response (pCR) and major pathological response (MPR) are associated with enhanced survival in those with NSCLC. The optimal TTS interval remains to be determined, some studies indicated that TTS ≤6 weeks has a vital role in NSCLC prognosis. Therefore, this study aimed to determine whether TTS is correlated with pathological outcomes and to identify the factors associated with TTS., Methods: We retrospectively analyzed 82 individuals who had surgery after neoadjuvant chemoimmunotherapy for NSCLC between January 2020 and December 2023. Fifty participants were included in this study after inclusion and exclusion criteria. Participants were categorized into two groups: TTS ≤4 weeks and TTS >4 to 6 weeks. Univariate and multivariate regression analyses were employed to determine the impact of TTS on pathological response and to identify the variables associated with TTS. Variables that showed their P value <0.2 in univariate analyses were included in the multivariate analysis. Kaplan-Meier analysis was used to analyze disease-free survival (DFS)., Results: Our study evaluating 50 patients revealed that patients in the TTS ≤4 weeks group achieved pCR or MPR compared to patients in the >4 to 6 weeks group (P=0.01). In univariate analyses, TTS ≤4 weeks was more correlated with achieving pCR or MPR than TTS >4 to 6 weeks [odds ratio (OR) =0.211; 95% confidence interval (CI): 0.062-0.711; P=0.01] The multivariate analysis showed that cT1 stage (compared to cT4), and cN1 stage (compared to cN0) showed statistical correlation with achieving pCR or MPR. cN1 stage was independent predictor of achieving pCR or MPR (OR =27.817; 95% CI: 1.536-503.88; P=0.02). Concerning to the DFS, TTS ≤4 weeks group and TTS >4 to 6 weeks group showed no statistical differences (2-year DFS rate were 70.6% and 72.6%, respectively). Regarding the tendency of being patients' TTS ≤4 weeks, patients with ventilatory impairment (OR =0.203; 95% CI: 0.04-0.98; P=0.047) were more tending to prolong the TTS to >4 to 6 weeks., Conclusions: TTS ≤4 weeks was associated with a significant improvement of pathological response. Therefore, patients with NSCLC should undergo surgery within 4 weeks after the last cycle of neoadjuvant chemoimmunotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-781/coif). A.R. serves as an unpaid editorial board member of Translational Lung Cancer Research from November 2022 to October 2024. A.R. owns stock options by IQVIA Holdings Inc. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Anastomotic leakage (AL) is one of the severest complications after laparoscopic surgery for middle/low rectal cancer, significantly impacting patient outcomes. Identifying reliable predictive factors for AL remains a clinical challenge. Serum nutritional biomarkers have been implicated in surgical outcomes but are underexplored as predictive tools for AL in this setting. Our study hypothesizes that preoperative serum levels of prealbumin (PA), albumin (ALB), and transferrin (TRF), along with surgical factors, can accurately predict AL risk., Aim: To determine the predictive value of preoperative serum nutritional biomarkers for rectal cancer AL following laparoscopic surgery., Methods: In the retrospective cohort study carried out at a tertiary cancer center, we examined 560 individuals who underwent laparoscopic procedures for rectal cancer from 2018 to 2022. Preoperative serum levels of PA, ALB, and TRF were measured. We employed multivariate logistic regression to determine the independent risk factors for AL, and a predictive model was constructed and evaluated using receiver operating characteristic curve analysis., Results: AL occurred in 11.96% of cases, affecting 67 out of 560 patients. Multivariate analysis identified PA, ALB, and TRF as the independent risk factor, each with an odds ratio of 2.621 [95% confidence interval (CI): 1.582-3.812, P = 0.012], 3.982 (95%CI: 1.927-4.887, P = 0.024), and 2.109 (95%CI: 1.162-2.981, P = 0.031), respectively. Tumor location (< 7 cm from anal verge) and intraoperative bleeding ≥ 300 mL also increased AL risk. The predictive model demonstrated an excellent accuracy, achieving an area under the receiver operating characteristic curve of 0.942, a sensitivity of 0.844, and a specificity of 0.922, demonstrating an excellent ability to discriminate., Conclusion: Preoperative serum nutritional biomarkers, combined with surgical factors, reliably predict anastomotic leakage risk after rectal cancer surgery, highlighting their importance in preoperative assessment., 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.)

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)

Cyanobacterial harmful algal blooms, particularly those dominated by Microcystis, pose significant ecological and health risks worldwide. This review provides an overview of the latest advances in biotechnological approaches for mitigating Microcystis blooms, focusing on cyanobactericidal bacteria, fungi, eukaryotic microalgae, zooplankton, aquatic plants, and cyanophages. Recently, promising results have been obtained using cyanobactericidal bacteria: not through the inoculation of cultured bacteria, but rather by nurturing those already present in the periphyton or biofilms of aquatic plants. Fungi and eukaryotic microalgae also exhibit algicidal properties; however, their practical applications still face challenges. Zooplankton grazing on Microcystis can improve water quality, but hurdles exist because of the colonial form and toxin production of Microcystis. Aquatic plants control blooms through allelopathy and nutrient absorption. Although cyanophages hold promise for Microcystis control, their strain-specificity hinders widespread use. Despite successful laboratory validation, field applications of biological methods are limited. Future research should leverage advanced molecular and bioinformatic techniques to understand microbial interactions during blooms and offer insights into innovative control strategies. Despite progress, the efficacy of biological methods under field conditions requires further verification, emphasizing the importance of integrating advanced multi-meta-omics techniques with practical applications to address the challenges posed by Microcystis blooms. KEY POINTS: • A diverse range of biotechnological methods is presented for suppressing Microcystis blooms. • Efficacy in laboratory experiments needs to be proved further in field applications. • Multi-meta-omics techniques offer novel insights into Microcystis dynamics and interactions., (© 2024. The Author(s).)

Immune checkpoint blockades are actively adopted in diverse cancer types including metastatic melanoma and lung cancer. Despite of durable response in 20-30% of patients, we still lack molecular markers that could predict the patient responses reliably before treatment. Here we present a composite model for predicting anti-PD-1 response based on tumor mutation burden (TMB) and transcriptome sequencing data of 85 lung adenocarcinoma (LUAD) patients who received anti-PD-(L)1 treatment. We found that TMB was a good predictor (AUC = 0.81) for PD-L1 negative patients (n = 20). For PD-L1 positive patients (n = 65), we built an ensemble model of 100 XGBoost learning machines where gene expression, gene set activities and cell type composition were used as input features. The transcriptome-based models showed excellent accuracy (AUC > 0.9) and highlighted the contribution of T cell activities. Importantly, nonresponder patients with high prediction score turned out to have high CTLA4 expression, which suggested that neoadjuvant CTLA4 combination therapy might be effective for these patients. Our data and analysis results provide valuable insights into developing biomarkers and strategies for treating LUAD patients using immune checkpoint inhibitors., (© 2024. The Author(s).)

The number of cyanobacterial harmful algal blooms (cyanoHABs) has increased, leading to the widespread development of prediction models for cyanoHABs. Although bacteria interact closely with cyanobacteria and directly affect cyanoHABs occurrence, related modeling studies have rarely utilized microbial community data compared to environmental data such as water quality. In this study, we built a machine learning model, the multilayer perceptron (MLP), for the prediction of Microcystis dynamics using both bacterial community and weekly water quality data from the Daechung Reservoir and Nakdong River, South Korea. The modeling performance, indicated by the R 2 value, improved to 0.97 in the model combining bacterial community data with environmental factors, compared to 0.78 in the model using only environmental factors. This underscores the importance of microbial communities in cyanoHABs prediction. Through the post-hoc analysis of the MLP models, we revealed that nitrogen sources played a more critical role than phosphorus sources in Microcystis blooms, whereas the bacterial amplicon sequence variants did not have significant differences in their contribution to each other. Similar to the MLP model results, bacterial data also had higher predictability in multiple linear regression (MLR) than environmental data. In both the MLP and MLR models, Microscillaceae showed the strongest association with Microcystis. This modeling approach provides a better understanding of the interactions between bacteria and cyanoHABs, facilitating the development of more accurate and reliable models for cyanoHABs prediction using ambient bacterial data., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the form and level of daily caffeine intake recommended above 400 mg in medical students expected to consume caffeinated beverages to enhance their performance., Methods: From May to June 2023, freshman through senior medical students at a medical school in Korea were administered a seven-item questionnaire designed to measure the amount of caffeine-containing foods consumed, the weekly interval between consumption, the reason for consumption, and the level of caffeine-induced symptoms experienced., Results: Out of 443 students, 361 responded (81.5%). The most commonly consumed caffeine beverages were coffee (79.2%), followed by soda (33.2%), tea (27.4%), chocolate (25.2%), and energy drinks (20.5%). The estimated (average±standard deviation) daily intake was estimated to 274.6±276.5 mg, and they consumed caffeine on an average of 4.25±2.26 days per week. Students who consumed 400 mg or more of caffeine daily consumed 19.9%. The primary motivation for caffeine intake was "to improve academic performance" (60.9%) and "preferred food" (51.8%). Among the responders, 98% of them replied they had symptoms that could be caused by caffeine, in order of palpitations (47.4%), frequent urination (42.9%), anxiety (27.1%), indigestion (17.5%), and excitement (17.5%). A total of 45.7% reported two symptoms, and 24.7% reported three or more., Conclusion: Caffeinated beverage consumption was routine among current medical students, with 20% consuming more than the recommended daily amount. Most students experienced at least one caffeine-induced symptom, with two symptoms in half, suggesting the need for policy measures and warnings about caffeine-containing foods.

The nasotracheal tube (NTT) is frequently used in oral and maxillofacial surgery and is generally considered a safe means of protecting the airway while ensuring an adequate surgical field. The most common complication associated with NTT is epistaxis, and only a few cases of foreign body obstruction have been reported. In this case report, the authors aimed to highlight the potential for NTT obstruction following surgery. A 24-year-old female patient, who underwent mandibuloplasty and rhinoplasty at a local clinic, was referred to our hospital patient due to dyspnea and edema on her right mandibular angle. Even with NTT, patient continued to experience mild dyspnea and tachypnea, so a T-piece was applied. However, tachycardia accompanied by a sudden worsening of dyspnea was observed, and bag-valve-mask ventilation was initiated promptly. But oxygen saturation remained unimproved, so an emergency cricothyroidotomy was performed. After 4 hours, the patient's condition stabilized. Upon examination, the previously inserted NTT was identified, and a blood clot approximately 10 cm long at the NTT tip was discovered, causing lumen obstruction. The obstructions of NTT can lead to serious or life-threatening consequences if left unobserved or ignored. Therefore, when a patient with an NTT complains of dyspnea, clinicians should promptly investigate the possibility of partial NTT obstruction to ensure the airway's security.

Objective: To investigate the differences in autonomic nervous system (ANS) dysfunction, arterial stiffness, and the degree of delay in post-exercise heart rate recovery (HRR) according to the level of spinal cord injury (SCI), and propose preventive measures against cardiovascular diseases after SCI., Methods: This retrospective study included 51 patients with SCI. Based on the neurological level of injury (NLI), patients were divided into two groups: Group A (NLI at and above T6) and Group B (NLI below T6). To assess ANS dysfunction, the head-up tilt test and 24-hour ambulatory blood pressure monitoring were conducted. Arterial stiffness was measured using the pulse wave velocity test. The exercise tolerance test was conducted to measure post-exercise HRR., Results: Group A had significantly higher values in the head-up tilt test and 24-hour ambulatory blood pressure monitoring. In the pulse wave velocity test, both sides (left and right) had significantly higher values in Group B. One minute after the exercise tolerance test, Group A had significantly slower HRR (18.8 ± 11.1 beats/minute) than Group B., Conclusion: Understanding the impact of ANS dysfunction and arterial stiffness on HRR in SCI according to NLI may provide insights for clinical management and preventative strategies for cardiovascular diseases., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Purpose: To determine the obstetric factors affecting the development of depressed skull fracture in neonates., Materials and Methods: This was a retrospectively cohort study on neonates born between July 2016 and August 2021. Neonates diagnosed with depressed skull fractures within one week of birth through X-ray and/or brain ultrasonography were included, and their mothers' obstetric characteristics were reviewed., Results: There were 12 cases in 6791 live births. Five women were over 35 years old. All except two were nulliparous. Five cases were delivered from labor induction and others presented with spontaneous labor. Except for two cases, delivery occurred within an hour after full cervical dilatation. Two cases were assisted by vacuum. None displayed fetal distress signs such as low Apgar scores below 7, meconium staining, and umbilical cord pH under 7.2. All depressed fractures were found in the right parietal area. Three cases resulted in focal hyperechoic lesion in brain ultrasonography and two of them showed small hemorrhage-like lesion in magnetic resonance imaging. All depressed skull fractures improved within 6 months in followed X-rays or ultrasonography., Conclusions: There was no definitely associated obstetric condition for depressed skull fracture of neonates although nulliparous women were majority of the affected cases., (© 2024. The Author(s).)

Background: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC., Methods: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC., Results: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group., Conclusion: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability., (© 2024. The Author(s).)

As genomic selection emerges as a promising breeding method for both plants and animals, numerous methods have been introduced and applied to various real and simulated data sets. Research suggests that no single method is universally better than others; rather, performance is highly dependent on the characteristics of the data and the nature of the prediction task. This implies that each method has its strengths and weaknesses. In this study, we exploit this notion and propose a different approach. Rather than comparing multiple methods to determine the best one for a particular study, we advocate combining multiple methods to achieve better performance than each method in isolation. In pursuit of this goal, we introduce and develop a computational method of the stacked generalization within ensemble methods. In this method, the meta-model merges predictions from multiple base models to achieve improved performance. We applied this method to plant and animal data and compared its performance with currently available methods using standard performance metrics. We found that the proposed method yielded a lower or comparable mean squared error in predicting phenotypes compared to the current methods. In addition, the proposed method showed greater resistance to overfitting compared to the current methods. Further analysis included statistical hypothesis testing, which showed that the proposed method outperformed or matched the current methods. In summary, the proposed stacked generalization integrates currently available methods to achieve stable and better performance. In this context, our study provides general recommendations for effective practices in genomic selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Chu, Park and Lee.)

Hierarchically porous materials containing sub-nm ultramicropores with molecular sieving abilities and microcavities with high gas diffusivity may realize energy-efficient membranes for gas separations. However, rationally designing and constructing such pores into large-area membranes enabling efficient H 2 separations remains challenging. Here, we report the synthesis and utilization of hybrid carbon molecular sieve membranes with well-controlled nano- and micro-pores and single zinc atoms and clusters well-dispersed inside the nanopores via the carbonization of supramolecular mixed matrix materials containing amorphous and crystalline zeolitic imidazolate frameworks. Carbonization temperature is used to fine-tune pore sizes, achieving ultrahigh selectivity for H 2 /CO 2 (130), H 2 /CH 4 (2900), H 2 /N 2 (880), and H 2 /C 2 H 6 (7900) with stability against water vapor and physical aging during a continuous 120-h test., (© 2024. The Author(s).)