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In Saudi Arabia, date palm biomass is often considered bulk waste, posing health risks to humans and the environment when incinerated or disposed of in landfills. This study explores the reuse of date palm biomass through cellulose extraction using Natural Deep Eutectic Solvent (NaDES) and Microwave-assisted process as compared with conventional alkali peroxide method. Characterization of the extracted cellulose was conducted using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), x-ray diffractometry (XRD), and fourier-transform infrared spectroscopy (FTIR). Our NaDES-microwave method produced a cellulosic product with a yield of 89 %, double that of conventional non-microwave methods and more rapid cellulosic extraction, indicating its favorable efficiency. Moreover, the incorporation of the microwave process resulted in larger cellulosic crystallite sizes and higher thermal stabilities in the produced samples. The utilization of NaDES and microwave-assisted process for cellulose extraction from date palm biomass not only demonstrates superior efficiency, but also accentuates a significant sustainability advantage by repurposing a prevalent waste stream, thereby mitigating environmental and health risks associated with traditional disposal methods., 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy., 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.)

Alkaline phosphatase (ALP) is an essential hydrolase widely present in humans, and it extensively acts as a biomarker for multiple human diseases. Conventional ALP assays suffer from complicated synthesis, tedious operation, low sensitivity, and large sample consumption. Herein, we construct an end-repairing-engineered quadratic in vitro transcription machine for single-molecule monitoring of ALP in diverse cancers with 3'-phosphoryl (PO 4 ) nucleic acid as a macromolecular substrate. In presence of ALP, it catalyzes the removal of 3'-PO 4 group to yield a 3'-hydroxyl end in hairpin probe 1 (HP1). Under the catalysis of Taq ligase, 3'-hydroxylated HP1 and hairpin probe 2 (HP2) are ligated together to form an intact transcription template. With the addition of T7 RNA polymerase, in vitro transcription amplification is activated to synthesize numerous reporter probes. Resulting reporter probes can bind with signal probes to initiate duplex-specific nuclease (DSN)-aided cyclic degradation of signal probes. Eventually, multiple cycles of degradation-liberation-hybridization induce the generation of large amounts of FAM fluorophores that are counted via single-molecule imaging. Due to high specificity of ALP-directed 3'-end dephosphorylation, high efficiency of quadratic in vitro transcription cascades, and ultrahigh signal-to-noise ratio (SNR) of single-molecule counting, this machine can detect ALP with a limit of detection (LOD) of 7.93 × 10 -8 U/μL in vitro and 1 cell in vivo. Furthermore, it can be applied for the evaluation of enzyme kinetics, screening of potential antidrugs, and quantification of ALP level in various cancer cells and human serums, holding potential in 3'-phosphatases-associated biological study and clinical diagnosis., 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.)

Introduction: Short Bowel Syndrome (SBS) is a rare gastrointestinal disorder associated with Intestinal Failure (SBS-IF) that leads to morbidity, mortality, and a burden on healthcare costs. Intestine Transplantation (IT) is a treatment option for patients with SBS-IF as it replaces the missing or diseased intestine and offers the potential for return to normal activities and intestinal function. This study aims to describe the clinical course and demographical and clinical characteristics of subjects with SBS-IF who underwent IT in Brazil., Methods: This retrospective observational study included all SBS-IF patients who underwent IT in two reference centers in Brazil from April 2011 to December 2021., Results: A total of 7 young male participants were included in the study. The most frequent underlying condition was surgical complications, followed by intestinal volvulus and incisional hernia. The most frequent indication for IT was a hepatic disease associated with total Parenteral Nutrition (PN). The main type of IT performed was intestine only. The median time from underlying condition to IT was 67.3 (16.5‒88.5) months. The mean (SD) number of yearly hospitalizations per patient was 0.5 (0.3). The most common reason for hospitalization was PN-related complications. Sixty exams were performed in-hospital and 53 in the outpatient setting., Conclusion: The findings of this study may be helpful to understand better the journey of patients with SBS-IF to IT in Brazil, providing real-world evidence to develop health policy guidelines and improve the quality of life of these patients., Competing Interests: Declaration of competing interest The authors declare the following conflicts of interest: YLB; MHMR; LH; RAAP: ADWL: APCSB; IC; GGR; FM; and LACA: Has acted as speaker in Takeda Distribuidora Ltda in medical-scope events. CYS and BF are employees of Takeda Distribuidora Ltda, Brazil., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Metabolic reprogramming precedes most alterations during pathological cardiac hypertrophy and heart failure (HF). Recent studies have revealed that Phosphofructokinase, platelet (PFKP) has a wealth of metabolic and non-metabolic functions. In this study, we explored the role of PFKP in cardiac hypertrophic growth and HF. The expression level of PFKP was elevated both in pathological cardiac remodeling mouse model challenged by transverse aortic constriction (TAC) surgery and in the neonatal rat cardiomyocytes (NRCMs) stimulated by phenylephrine (PE). In global PFKP knockout (PFKP-KO) mice, cardiac hypertrophy was ameliorated under TAC surgery, while overexpression of PFKP by intravenous injection of adeno-associated virus 9 (AAV9) under the cardiac troponin T (cTnT) promoter worsened myocardial hypertrophy and fibrosis. In NRCMs, small interfering RNA (SiRNA) knockdown or adenovirus (Adv) overexpression of PFKP was employed and the intervention of PFKP showed a similar phenotype. Mechanistically, immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP-MS/MS) analysis was used to identify the interacting proteins of PFKP. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) was identified as the downstream target of PFKP. In the PE-stimulated NRCM hypertrophy model and mouse TAC model, knocking down EIF2S2 after PFKP overexpression reduced the synthesis of new proteins and alleviated the hypertrophy phenotype. Our findings illuminate that PFKP participates in pathological cardiac hypertrophy partly by regulating protein synthesis through EIF2S2, which provides a new clue for the involvement of metabolic intermediates in signal transduction., 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 B.V. All rights reserved.)

Forsythin, currently in phase II clinical trials in China for the treatment of the common cold and influenza, faces challenges in achieving adequate lung drug exposure due to its limited dissolution and permeability, thereby restricting its therapeutic efficacy. The objective of this work was to formulate a forsythin-phospholipid complex (FPC) to enhance its dissolution properties and lung affinity with a particular view to improving pulmonary drug exposure and anti-inflammatory response. The results revealed that forsythin reacted with dipalmitoyl-phosphatidylcholine to form a stable, nanosized FPC suspension. This formulation significantly improved the in vitro drug's dissolution, cellular uptake, and lung affinity compared to its uncomplexed form. Intratracheal administration of FPC in a mouse model of acute lung injury induced by lipopolysaccharide (LPS) resulted in a substantial increase in drug exposure to lung tissues (39.6-fold) and immune cells in the epithelial lining fluid (198-fold) compared to intraperitoneal injection. In addition, FPC instillation exhibited superior local anti-inflammatory effects, leading to improved survival rates among mice with LPS-induced acute respiratory distress syndrome, outperforming both instilled forsythin and injected FPC. Overall, this work demonstrated the potential of phospholipid complexes as a viable option for developing inhalation products for drugs with limited solubility and permeability properties., 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.)

Triclosan (TCS) is an antimicrobial agent commonly used in personal care products. However, little is known about its toxicity to corals. Here, we examined the acute toxic effects (96 h) of TCS at different levels to the coral Porites lutea. Results showed that the bioaccumulation factors (BAFs) of TCS in Porites lutea decreased with increasing TCS exposure levels. Exposure to TCS at the level up to 100 μg/L did not induce bleaching of Porites lutea. However, by the end of the experiment, both the density and chlorophyll a content of the symbiotic zooxanthellae were 19-52 % and 19.9-45.6 % lower in the TCS treatment groups than in the control, respectively. For the coral host, its total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activities were all significantly lower in the TCS treatment groups than the control. Transcriptome analysis showed that 942 and 1077 differentially expressed genes (DEGs) were identified in the coral host in the 0.5 and 100 μg/L TCS treatment groups, respectively. Meanwhile, TCS can interfere with pathways related to immune system and reproductive system in coral host. Overall, our results suggest that environmentally relevant concentrations of TCS can impact both the coral host and the symbiotic zooxanthellae., 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.)

Objective: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes., Methods: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed., Results: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes., Conclusion: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC 50 values of 29.65, 23.41, 18.12 and 26.64 μM, respectively, as compared with the positive control (dexamethasone, IC 50 value: 40.35 μM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner., 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.)

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis, and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Backgrounds: Ample evidence supports potential influence of age at menarche (AM) on adult height (AH), but multiple confounders may affect causal estimates. To address this issue, the Mendelian randomization (MR) analysis was used to explore the causal impacts of AM on AH., Methods: Using data (n = 57,349) from the publicly accessible Taiwan Biobank and randomly splitting them into 2 equal-size subsets, we identified single nucleotide polymorphisms (SNPs) significantly associated with AM in the exploration subset and used these SNPs as instrumental variables to estimate the effects of instruments on AH in the validation subset based on two stage least squares (2SLS) regression. In addition, three more summary statistics-based approaches, namely inverse variance weighted (IVW), MR-Egger, and weighted median (WM) analyses, were used to verify the findings. We also performed heterogeneity and sensitivity analyses to evaluate the robustness of the results., Results: We identified 4 leading SNPs associated with AM at the genome-wide significant level, whereas rs9409082 may exert some pleiotropic effects on AH. After eliminating rs9409082, the 2SLS analysis indicated that one year delay in genetically determined AM predicted 1.5 cm height gain in adulthood (β = 1.508, 95% confidence interval [0.852, 2.163]). The causal relationship was also supported by WM (β = 1.183, [0.329, 2.038]) and IVW (β = 1.493, [0.523, 2.463]) methods., Conclusions: Evidence from the present MR study supports a causal relationship between later AM and taller AH., Competing Interests: Declaration of Competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Vascular complications increase morbidity and mortality after transcatheter aortic valve replacements (TAVR), often related to failures in vascular closure devices (VCDs). We intended to compare the dual Perclose ProGlide (PP) strategy and the hybrid combination of PP and Angio-Seal (AS) for femoral access hemostasis after TAVR., Methods: A randomised controlled trial with 257 patients comparing dual PP with 1 PP and 1 AS (AS+PP) for vascular closure after transfemoral TAVR was conducted. The primary end point was the composite of TAVR access site-related vascular complications and life-threatening type 2/3 or 1 bleeding according to the Valve Academic Research Consortium 3. Secondary end points included additional VCD use and significant peripheral ischemia related to arteriotomy closure within 1 year. Modified VCD failure, defined as failure to achieve hemostasis within 5 minutes or requiring additional endovascular manoeuvres, was also recorded., Results: The AS+PP combination yielded lower rates of the primary end point (18.2% vs 29.8%; P = 0.0381), vascular complication (18.2% vs 29.8%; P = 0.0381), additional VCD use (0.8% vs 19.0%; P < 0.0001), and modified VCD failure (9.9% vs 33.1%; P < 0.0001) than the dual PP. Bleeding complication rates were similar between the 2 groups. Three-month follow-up vascular duplex tests showed similar common femoral artery (CFA) diameters and peak systolic velocities (PSVs) between the 2 groups, but those with additional intervention had higher PSVs and smaller CFA diameters than those without., Conclusions: Combined PP+AS for large-bore femoral access hemostasis after TAVR promises to be more effective and safer than dual PP in terms of vascular complications. Moreover, additional intervention for vascular complications resulted in smaller CFA diameters., Clinical Trial Registration: NCT05491070., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Arsenic is a toxic element widely distributed in the Earth's crust and ranked as a class I human carcinogen. Microbial metabolism makes significant contributions to arsenic detoxification, migration and transformation. Nowadays, research on arsenic is primarily in areas affected by arsenic pollution associated with human health activities. However, the biogeochemical traits of arsenic in the global marine ecosystem remain to be explicated. In this study, we revealed that seawater environments were primarily governed by the process of arsenate reduction to arsenite, while arsenite methylation was predominant in marine sediments which may serve as significant sources of arsenic emission into the atmosphere. Significant disparities existed in the distribution patterns of the arsenic cycle between surface and deep seawaters at middle and low latitudes, whereas these situations tend to be similar in the Arctic and Antarctic oceans. Significant variations were also observed in the taxonomic diversity and core microbial community of arsenic cycling across different marine environments. Specifically, γ-proteobacteria played a pivotal role in the arsenic cycle in the whole marine environment. Temperature, dissolved oxygen and phosphate were the crucial factors that related to these differentiations in seawater environments. Overall, our study contributes to a deeper understanding of the marine arsenic cycle., 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.)

Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis, and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in 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 Elsevier B.V. All rights reserved.)

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery., 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.)

O 6 -methylguanine methyltransferase (MGMT) is responsible for dealkylation of naturally occurring O 6 -methylguanines, and it is closely related with DNA replication, transcription, and cancers. Herein, we develop a chemiluminescent biosensor based on enzymatic extension and click chemistry for sensitive measurement of MGMT activity. When MGMT is present, the MGMT-catalyzed demethylation reaction initiates the cleavage of biotinylated dumbbell probes by PvuII restrictive enzyme, releasing two DNA fragments with 3'-OH end. The resultant DNA fragments can trigger terminal transferase (TdT)- and click chemistry-assisted isothermal amplification to obtain abundant G-rich sequences. The G-rich sequences can be captured by magnetic beads to produce a high chemiluminescence signal. This biosensor can greatly amplify the chemiluminescence signal, facilitating label-free and template-free measurement of MGMT. Especially, the introduction of dumbbell probe and PvuII enzyme can efficiently eliminate the false positive and improve the assay specificity. This biosensor possesses high sensitivity with a detection limit of 1.4 × 10 -9  ng/μL, and it may accurately quantify the intracellular MGMT. Importantly, this biosensor can be used to screen the MGMT inhibitors and distinguish the MGMT level in breast tumor tissues and normal tissues, with great potential in drug discovery and cancer diagnosis., 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.)

Flap endonuclease 1 (FEN1) is a structure-specific nuclease that can specially identify and cleave 5' flap of branched duplex DNA, and it plays a critical role in DNA metabolic pathways and human diseases. Herein, we propose a simple "mix-and-detection" strategy for sensitive measurement of human cellular FEN1 on basis of template-free amplification. We design a dumbbell probe with 5' flap as a substrate of FEN1 and a NH 2 -labeled 3' termini to prevent nonspecific amplification. When FEN1 is present, the 5' flap is cleaved to release a free 3'-OH termini, initiating Ribonuclease HII (RNase HII)-assisted terminal deoxynucleotidyl transferase (TdT)-induced amplification for the production of a significant fluorescence signal. Due to the high exactitude of TdT-mediated extension reaction and RNase HII-induced single ribonucleotide excise, this assay shows excellent specificity and high sensitivity with a detection limit of 5.64 × 10 -6 U/μL. Importantly, it can detect intracellular FEN1 activity with single-cell sensitivity under isothermal condition in a "mix-and-detection" manner, screen the FEN1 inhibitors, and even discriminate tumor cells from normal cells, offering a new platform for disease diagnosis and drug discovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The metabolites from the endophytic fungus Talaromyces malicola hosted in the gastrointestinal tract of the arthropods Armadillidium vulgare were investigated, and six undescribed fusicoccane diterpenoids, talarmalnoids A-F (1-6), along with three known analogs were isolated. Talarmalnoid C (3) was an unprecedented fusicoccane diterpenoid with two sugar units, i.e., 6-O-methyl-α-d-glucose and α-d-glucose. Talarmalnoids D and E (4 and 5) were fusicoccane-type diterpenoids with unusual seven-membered rings attached at the C-3' and C-4' positions. Their structures and absolute configurations were identified by NMR, HRESIMS analyses, X-ray single crystal diffraction, GC-MS, ECD analyses, 13 C NMR calculations, and DP4+ probability analyses. Bioassay results showed that talarmalnoid B (2) exhibited significant inhibitory activities against the LPS-inducted production of NO in RAW 264.7 cells, with IC 50 value of 0.83 μM., 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.)

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2 nd and 3 rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2 nd trimester phthalates mixture and sex on FEV 1 and FVC z-scores. Higher 2 nd trimester phthalate concentrations were associated with higher FEV 1 (β = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (β = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV 1 , β = -0.017, 95 %CI: -0.066, 0.026; FVC, β = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner., 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.)

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of bio‑sulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/objective: The Tomita, revised Tokuhashi and Tokuhashi lung scores are commonly used tools to predict the survival of patients with spinal metastases and to guide decisions regarding surgical treatment. These prognostic scores, however, tend to underestimate the prognosis of patients with lung cancer. We examined surgical outcome and hopefully provide a more accurate reference for management., Methods: The consistency between predicted and actual survival was examined using the Tomita and Tokuhashi scores. Various factors that may influence survival were analyzed. Primary outcomes were overall survival (OS) and progression-free survival (PFS), defined as the ambulatory time after the initial surgery. Secondary outcomes included reoperation events, blood loss, and hospitalization days., Results: One hundred seventy-two patients were enrolled. Correct survival predictions were made for 28%, 42%, and 56% with the Tomita, revised Tokuhashi, and Tokuhashi lung scores, respectively. The Tokuhashi lung scores underestimated OS by 35%-40%. Body mass index ≥20, systemic treatment-naïve, good general condition, the use of denosumab, and adenocarcinoma were found to positively affect OS and PFS. There was no significant difference between palliative decompression and excisional surgery regarding OS and PFS., Conclusion: Patients with spinal metastases from lung cancer had better prognosis than that predicted by the Tomita and Tokuhashi scores. Spine surgeons should acknowledge this discrepancy and treat these patients with at least the aggressiveness suggested. Patients with adenocarcinoma, amenable to target therapy, denosumab, good general condition, systemic treatment-naïve are better candidates for surgery. Those with cachexic status and unresectable visceral metastases are worse candidates., Competing Interests: Declaration of competing interest All of the authors have no conflicts of interest to declare., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Objective: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes., Methods: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines., Results: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline., Conclusion: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to evaluate the influence of ultrasonic degradation on the physicochemical and biological characteristics of Polygonatum cyrtonema polysaccharide (PCP, 8.59 kDa). PCP was subjected to ultrasonic treatment for 8, 16, and 24 h and yielded the degraded fractions PCP-8, PCP-16, and PCP-24 (5.06, 4.13, and 3.69 kDa), respectively. Compared with the intact PCP, PCP-8, PCP-16 and PCP-24 had a reduced particle size (decrements of 28.03 %, 46.15 % and 62.54 %, respectively). Although ultrasonic degradation did not alter the primary structure of PCP, its triple helical and superficial structures were disrupted, with degraded fractions demonstrating reduced thermal stability and apparent viscosities compared with those of the intact PCP. Furthermore, the functional properties of the degraded fractions were different. PCP-16 most favourably affected GLP-1 secretion, while PCP-8 and PCP-24 exhibited the strongest antioxidant and enzyme inhibitory activities, respectively. Hence, controlled ultrasound irradiation is an appealing approach for partially degrading PCP and enhancing its bioactivity as a functional agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aberrant long noncoding RNA (lncRNA) expression is linked to varied pathological processes and malignant tumors, and lncRNA can serve as potential disease biomarkers. Herein, we demonstrate the autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of lncRNA in human lung tissues on the basis of multiple primer generation-mediated rolling circle amplification (mPG-RCA). This assay involves two padlock probes that act as both a detection probe for recognizing target lncRNA and a domain for producing complementary DNAzyme. Two padlock probes can hybridize with target lncRNA at different sites, followed by ligation to form a circular template with the aid of RNA ligase. The circular template can initiate mPG-RCA to generate abundant Mg 2+ -dependent DNAzymes that can specifically cleave signal probes to induce the recovery of Cy3 fluorescence. The inherent characteristics of ligase-based ligation reaction and DNAzymes endow this assay with excellent specificity, and the introduction of multiple padlock probes endows this assay with high sensitivity. This strategy can rapidly and sensitively measure lncRNA with a wide linear range of 1 fM - 1 nM and a detection limit of 678 aM within 1.5 h, and it shows distinct advantages of simplicity and immobilization-free without the need of precise temperature control and tedious procedures of nanomaterial preparation. Moreover, it enables accurate measurement of lncRNA level in normal cells and malignant tumor cells as well as differentiation of lncRNA expressions in tissues of non-small cell lung cancer (NSCLC) patients and normal individuals, with promising applications in biomedical studies and disease diagnosis., 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.)

Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN) 6 ] 3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL -1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL -1 , sensitivity of 32.25 μA∙pg -1 ∙mL∙cm -2 , RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL -1 -5.00 pg∙mL -1 ) with a LOD of 16.53 fg∙mL -1 , ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality., 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.)

SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2., Competing Interests: Declaration of competing interest We have no conflicts of interest associated with this publication. I confirmed that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2024. Published by Elsevier Inc.)

Poleward range expansion of marine organisms is commonly attributed to anthropogenic ocean warming. However, the extent to which a single species can migrate poleward remains unclear. In this study, we used molecular data to examine the current distribution of the Pocillopora damicornis species complex in Taiwan waters and applied niche modeling to predict its potential range through the end of the 21st Century. The P. damicornis species complex is widespread across shallow, tropical and subtropical waters of the Indo-Pacific regions. Our results revealed that populations from subtropical nonreefal coral communities are P. damicornis, whose native geographical ranges are approximately between 23°N and 35°N. In contrast, those from tropical reefs are P. acuta. Our analysis of 50 environmental data layers demonstrated that the concentrations of CaCO 3 polymorphs had the greatest contributions to the distributions of the two species. Future projections under intermediate shared socioeconomic pathways (SSP) 2-4.5 and very high (SSP5-8.5) scenarios of greenhouse gas emissions showed that while sea surface temperature (SST) isotherms would shift northwards, saturation isolines of two CaCO 3 polymorphs, calcite (Ωcal) and aragonite (Ωarag), would shift southwards by 2100. Subsequent predictions of future suitable habitats under those conditions indicated that distinct delimitation of geographical ranges for the two species would persist, and neither would extend beyond its native geographical zones, indicating that tropical Taiwan waters are the northern limit for P. acuta. In contrast, subtropical waters are the southern limit for P. damicornis. We concluded that the decline in CaCO 3 saturation would make high latitudes less inhabitable, which could be one of the boundary elements that limit poleward range expansion driven by rising SSTs and preserve the latitudinal diversity gradient (LDG) on Earth. Consequently, poleward migration of tropical reef corals to cope with warming oceans should be reevaluated., 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.)

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mei-Ling Sun reports financial support was provided by Fundamental Research Funds for the Central Universities. Mei-Ling Sun reports financial support was provided by National Key Research and Development Program of China. Peng Wang reports financial support was provided by National Natural Science Foundation of China. Hui-hui Fu reports financial support was provided by National Natural Science Foundation of China. Chun-Yang Li reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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.)

An efficient and sensitivity approach, which combines solid-phase extraction or ultrasonic extraction for pretreatment, followed by ultra-performance liquid chromatography-tandem mass spectrometry, has been established to simultaneously determine eight lipophilic phycotoxins and one hydrophilic phycotoxin in seawater, sediment and biota samples. The recoveries and matrix effects of target analytes were in the range of 61.6-117.3 %, 55.7-121.3 %, 57.5-139.9 % and 82.6 %-95.0 %, 85.8-106.8 %, 80.7 %-103.3 % in seawater, sediment, and biota samples, respectively. This established method revealed that seven, six and six phycotoxins were respectively detected in the Beibu Gulf, with concentrations ranging from 0.14 ng/L (okadaic acid, OA) to 26.83 ng/L (domoic acid, DA) in seawater, 0.04 ng/g (gymnodimine-A, GYM-A) to 2.75 ng/g (DA) in sediment and 0.01 ng/g (GYM-A) to 2.64 ng/g (domoic acid) in biota samples. These results suggest that the presented method is applicable for the simultaneous determination of trace marine lipophilic and hydrophilic phycotoxins in real samples., 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.)

Competing Interests: Declaration of Competing Interest The authors declare that the content of this paper was not affected by any financial, commercial, legal, or professional interest.

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection., Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI)., Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported., Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings., Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136., Competing Interests: This work was supported by National Key Research and Development Project: Adding Chinese herbal medicine to antibiotic treatment for acute exacerbation of chronic obstructive pulmonary disease (Grant No. 2018YFE0102300) and Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No:ZYYCXTD-C-202006)., (© 2024 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Fat mass and obesity-associated protein (FTO) is a crucial eraser of RNA N 6 - methyladenosine (m 6 A) modification, and abnormal FTO expression level is implicated in pathogenesis of numerous cancers. Herein, we demonstrate the construction of a label-free fluorescent biosensor for homogeneous detection of m 6 A eraser FTO in breast cancer tissues. When FTO is present, it specifically erases the methyl group in m 6 A, inducing the cleavage of demethylated DNA by endonuclease DpnII and the generation of a single-stranded DNA (ssDNA) with a 3'-hydroxyl group. Subsequently, terminal deoxynucleotidyl transferase (TdT) promotes the incorporation of dTTPs into the ssDNA to obtain a long polythymidine (T) DNA sequence. The resultant long poly (T) DNA sequence can act as a template to trigger hyperbranched strand displacement amplification (HSDA), yielding numerous DNA fragments that may be stained by SYBR Gold to produce an enhanced fluorescence signal. This biosensor processes ultrahigh sensitivity with a detection limit of 1.65 × 10 -10  mg/mL (2.6 fM), and it can detect the FTO activity in a single MCF-7 cell. Moreover, this biosensor can screen the FTO inhibitors, evaluate enzyme kinetic parameters, and discriminate the FTO expression levels in the tissues of breast cancer patients and healthy persons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The reported organic electrochemiluminescence (ECL) luminophors for the detection of various markers often suffer from intermolecular π-π stacking-induced luminophore quenching. Herein, we demonstrate one-pot synthesis of a new aggregation-induced electrochemiluminescence (AIECL) emitter (i.e., TPE@SiO 2 /rGO composite) for sensitive measurement of microcystin-leucine arginine (MC-LR). The TPE@SiO 2 /rGO composite is constructed by embedding the silica-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) in the reduced graphene oxide. In comparison with the monomer TPE, this composite exhibit high luminescence efficiency and strong ECL emission, because the AIECL phenomenon triggered by the spatial confinement effect in the SiO 2 cage induces the restriction of the internal motion and vibration of molecules. Notably, this composite has distinct advantages of easy preparation, simple functionalization, and stable luminescence. Especially, the TPE@SiO 2 /rGO-based ECL-RET system exhibits a high quenching efficiency (Φ ET ) of 69.7%. When target MC-LR is present, it triggers DNA strand displacement reaction (SDR), inducing the quenching of the ECL signal of TPE@SiO 2 /rGO composite due to ECL resonance energy transfer between TPE@SiO 2 /rGO composite and methylene blue (MB). The proposed biosensor enables highly sensitive, low-cost, and robust measurement of MC-LR with a large dynamic range of 7 orders of magnitude and a detection limit of 3.78 fg/mL, and it displays excellent detection performance in complex biological matrices, holding potential applications in food safety and water monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD)., Methods: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h 2 ) and genetic correlations (r g ) and modeled underlying factor structures with multivariate models., Results: Early-life vocabulary size was modestly heritable (SNP-h 2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (r g  = 0.07), although each measure was moderately related to toddler expressive vocabulary (r g  = 0.69 and r g  = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: r g  = 0.58 and r g  = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: r g  = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (r g  = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; r g  = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (r g  = -0.74), highlighting developmental heterogeneity., Conclusions: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels., 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. Availability of data and materials. All data used to support the findings of this study are available from the corresponding author upon request., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The trajectories of all-cause deaths linked to omicron infections are rarely studied, especially in relation to the efficacy of booster shots. For assessing three epidemiological death trajectories, including dying from COVID-19, dying with COVID-19, and non-COVID-19 death, we offer a new COVID-19-and-death competing risk model that deals with the primary pathway (e.g., dying from COVID-19) competing with two other pathways., Methods: We applied this model to track three trajectories: deaths directly from COVID-19, deaths with COVID-19 as a contributing factor, and indirect non-COVID-19 deaths. The study used data from a Taiwanese cohort, covering periods of Omicron subvariants BA.2, BA.5, and BA.2.75. It focused on the effectiveness of monovalent and bivalent booster vaccines against these death trajectories., Results: The highest mortality was observed during the BA.2 phase, which decreased in the BA.5 period and increased again in the BA.2.75 period. Analyzing each trajectory, we noted similar trends in deaths directly from and with COVID-19, while non-COVID-19 deaths remained stable across subvariants. Booster vaccines reduced all-cause mortality by 58% (52%-62%) for BA.2, 70% (65%-75%) for BA.5%, and 75% (70%-80%) for BA.2.75, compared to incomplete vaccination. The reduction in deaths directly from COVID-19 was 66% (61%-72%) for BA.2, 78% (72%-84%) for BA.5%, and 85% (76%-93%) for BA.2.75. For deaths with COVID-19, the figures were 46% (36%-55%), 76% (68%-84%), and 90% (86%-95%). Additionally, the booster shots decreased non-COVID-19 deaths by 64% (63%-66%) for BA.2, 38% (36%-40%) for BA.5, and 19% (17%-21%) for BA.2.75., Conclusion: Our competing risk analysis is effective for monitoring all-cause death trajectories amidst various Omicron infections. It provides insights into the impact of booster vaccines, especially bivalent ones, and highlights the consequences of inadequate healthcare for vulnerable groups., 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.)

Background: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results., Methods: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated., Results: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM 2.5 (β = -0.084, 95 % CI: -0.521, 0.353; I 2  = 93 %) and PM 10 (β = 0.035, 95 % CI: -0.129, 0.199; I 2  = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM 2.5 (β = 0.023, 95 % CI: -0.087, 0.133; I 2  = 0 %) and PM 10 (β = 0.006, 95 % CI: -0.135; 0.147; I 2  = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate.", Conclusions: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: 5-hydroxymethylcytosine (5hmC) as an epigenetic modification can regulate gene expression, and its abnormal level is related with various tumor invasiveness and poor prognosis. Nevertheless, the current methods for 5hmC assay usually involve expensive instruments/antibodies, radioactive risk, high background, laborious bisulfite treatment procedures, and non-specific/long amplification time., Results: We develop a glycosylation-mediated fluorescent biosensor based on helicase-dependent amplification (HDA) for label-free detection of site-specific 5hmC in cancer cells with zero background signal. The glycosylated 5hmC-DNA (5ghmC) catalyzed by β-glucosyltransferase (β-GT) can be cleaved by AbaSI restriction endonuclease to generate two dsDNA fragments with sticky ends. The resultant dsDNA fragments are complementary to the biotinylated probes and ligated by DNA ligases, followed by being captured by magnetic beads. After magnetic separation, the eluted ligation products act as the templates to initiate HDA reaction, generating abundant double-stranded DNA (dsDNA) products within 20 min. The dsDNA products are measured in a label-free manner with SYBR Green I as an indicator. This biosensor can measure 5hmC with a detection limit of 2.75 fM and a wide linear range from 1 × 10 -14 to 1 × 10 -8  M, and it can discriminate as low as 0.001% 5hmC level in complex mixture. Moreover, this biosensor can measure site-specific 5hmC in cancer cells, and distinguish tumor cells from normal cells., Significance: This biosensor can achieve a zero-background signal without the need of either 5hmC specific antibody or bisulfite treatment, and it holds potential applications in biological research and disease diagnosis., 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.)

DNA-modifying enzymes act as critical regulators in a wide range of genetic functions (e.g., DNA damage & repair, DNA replication), and their aberrant expression may interfere with regular genetic functions and induce various malignant diseases including cancers. DNA-modifying enzymes have emerged as the potential biomarkers in early diagnosis of diseases and new therapeutic targets in genomic research. Consequently, the development of highly specific and sensitive biosensors for the detection of DNA-modifying enzymes is of great importance for basic biomedical research, disease diagnosis, and drug discovery. Single-molecule fluorescence detection has been widely implemented in the field of molecular diagnosis due to its simplicity, high sensitivity, visualization capability, and low sample consumption. In this paper, we summarize the recent advances in single-molecule counting-based biosensors for DNA-modifying enzyme (i.e, alkaline phosphatase, DNA methyltransferase, DNA glycosylase, flap endonuclease 1, and telomerase) assays in the past four years (2019 - 2023). We highlight the principles and applications of these biosensors, and give new insight into the future challenges and perspectives in the development of single-molecule counting-based biosensors., 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.)

Injuries of the posterior root of the medial meniscus can be accompanied by damage to the anterior cruciate ligament or often occur independently in cases of degenerative meniscal injury in older individuals. Anchor suture repair can achieve favorable biomechanical effects and clinical outcomes. However, anchor placement is technically challenging and requires a posterior medial approach, which increases the risk of iatrogenic injury. To address these issues, we have utilized the reverse anchor technique to repair the posterior root of the medial meniscus. This technique offers advantages such as reduced surgical time, simplified operation, and reduced risk of the "bungee effect" and iatrogenic injury., Competing Interests: The authors report no conflicts of interest in the authorship and publication of this article. This work was supported by the Inner Mongolia Autonomous Region science and technology program (2022YFSH0028 and 2022YFSH0029) and Inner Mongolia Autonomous Region health science and technology project (202201344) and Inner Mongolia Medical University Science and technology innovation project (YKD2022TD007) and Inner Mongolia Autonomous Region public hospital high level clinical Specialist development technology program (2023SGGZ140 and 2023SGGZ138). Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2024 The Authors.)

Insecticide resistance is an evolved ability to survive insecticide exposure. Compared with nonsocial insects, eusocial insects have lower numbers of documented cases of resistance. Eusocial insects include beneficial and pest species that can be incidentally or purposely targeted with insecticides. The central goal of this review is to explore factors that either limit resistance or the ability to detect it in eusocial insects. We surveyed the literature and found that resistance has been documented in bees, but in other pest groups such as ants and termites, the evidence is more sparse. We suggest the path forward for better understanding eusocial resistance should include more tractable experimental models, comprehensive geographic sampling, and targeted testing of the impacts of social, symbiont, genetic, and ecological factors., 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.)

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of βPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of βPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and βPS integrins and partially rescued the detachment phenotype in flies with reduced βPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: In early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear., Methods: Patients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5., Results: We analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001)., Conclusion: For early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Children can become anxious when undergoing emergency medical treatment. Therefore, emergency departments should be child friendly. This study explored emergency nurses' perspectives on children's needs during emergency care., Method: This qualitative study employed purposive sampling to recruit 17 emergency nurses from 3 medical centers in northern and central Taiwan. Individual interviews were conducted between January and August 2021. Data were analyzed through qualitative content analysis., Results: The participants had 2-23 years of experience in caring for children in emergency departments. We identified 208 unique meaning units in the interview data, 79 of which were related to child-friendly emergency care. These were classified into 42 codes across 6 categories and 27 subcategories. The six categories were timely comfort, emotional care, frontline safety, emergency response, human resources support, and treatment efficiency., Conclusion: Emergency nurses have professional competencies, play a crucial role as care providers for children in the emergency department, and ensure the comfort and safety of children seeking treatment. The categories related to child-friendly emergency care identified in this study can serve as a basis for developing child-friendly care emergency guidelines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)