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Olusola Olawoye,1,2 Tarela Sarimiye,1,2 Adeyinka Ashaye,1,2 Young Hoon Hwang,3 Jong Chul Han,4 Byung Heon Ahn3 1Department of Ophthalmology, College of Medicine, University of Ibadan, 2Department of Ophthalmology, University College Hospital, Ibadan, Nigeria; 3Department of Ophthalmology, Konyang University, Kim’s Eye Hospital, Myung-Gok Eye Research Institute, 4Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea Purpose: The aim of this study was to report the safety and efficacy of the membrane-tube (MT)-type glaucoma shunt device (Finetube MT) in the management of refractory glaucoma in indigenous West Africans.Methods: The Finetube MT was implanted into 25 eyes of 25 West African patients with refractory glaucoma. These patients had inadequate intraocular pressure (IOP) control despite maximum tolerable IOP-lowering medications with or without previous ocular surgeries. IOP, postoperative complications, interventions, visual acuities, and the number of IOP-lowering medications were analyzed preoperatively and postoperatively.Results: The mean (standard deviation [SD]) age of the patients was 49.7 (20.9) years. The mean (SD) follow-up duration was 21.0 (10.6) months. Postoperatively, the mean (SD) IOP reduced from a preoperative value of 38.1 (10.3) mmHg to 14.5 (4.6), 16.1 (7.8), and 14.7 (3.0) mmHg at 1, 2, and 3 years postoperatively, respectively, representing 61.9%, 57.7%, and 61.4% reduction from baseline (P

Depletion in dissolved oxygen (DO) occurred in 2 semi-enclosed shallow bays in Korea in which Crassostrea gigas were suspended for aquaculture. DO depletion started at the bottom and expanded rapidly upwards for days until it was blocked by a temperature-driven density differential. This resulted in the formation of pelagic oxyclines at a depth of 2ñ4 m in one bay (Hypoxic Site 1, HS-1) and 2ñ5 m in the other (Hypoxic Site 2, HS-2). Water above the oxycline was normoxic (>4 mg l-1), while water below the oxycline was hypoxic (

Background/aims: To identify whether an intact retinal nerve fibre layer (RNFL) thickness profile could determine the location of the earliest RNFL defect in glaucoma., Methods: Retrospective longitudinal cohort study of patients with initial unilateral glaucoma who eventually developed new glaucoma in the fellow eye. Guided progression analysis (GPA) of serial optical coherence tomography (OCT) examinations was used to identify the angular locations of the earliest RNFL defect, peak and temporal edge of the baseline RNFL profile and major vessels based on the peripapillary OCT scan circle., Results: We identified 112 new RNFL defects in 109 fellow eyes of 109 consecutive patients. The locations of new defects were superotemporal (22 eyes), inferotemporal (87 eyes) and papillomacular bundle (3 eyes), respectively. Overall, the midpoint location of the earliest RNFL defect strongly coincided with the RNFL peak (p<0.001). Specifically, the location was mildly (4.3±12.0°) temporal to, rather than at the peak thickness, particularly in eyes with a focal thinning pattern of arcuate bundles (7.8±10.8°). The close topographical relationship was consistent regardless of the interindividual variability in the RNFL profile and vessels, as well as hemispheric locations, and after adjusting for potential factors including age, refractive error, baseline intraocular pressure, tilt ratio, tilt axis and glaucoma diagnosis., Conclusion: The location of the earliest RNFL defect in glaucoma showed a close relationship with the intact RNFL profile within the same eye, regardless of variations in RNFL, hemispheric location and vessel distribution. In addition, the earliest defect was located mildly temporal to, rather than at, the peak RNFL thickness. The baseline RNFL profile may have a significant role in the regional vulnerability of glaucoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The objective of this study was to gain insight into the nature of cognitive fatigue and to identify future trends of objective assessment techniques in this field., Methods: One thousand and eighty-five articles were retrieved from the Web of Science Core Collection database. R version 4.3.1, VOSviewer 1.6.20, CiteSpace 6.2.R4, and Microsoft Excel 2019 were used to perform the analysis., Results: A total of 704 institutes from 56 countries participated in the relevant research, while the People's Republic of China contributed 126 articles and was the leading country. The most productive institute was the University of Gothenburg. Johansson Birgitta from the University of Gothenburg has posted the most articles ( n  = 13). The PLOS ONE published most papers ( n  = 38). The Neurosciences covered the most citations ( n  = 1,094). A total of 3,116 keywords were extracted and those with high frequency were mental fatigue, performance, quality-of-life, etc. Keywords mapping analysis indicated that cognitive fatigue caused by continuous work and traumatic brain injury, as well as its rehabilitation, have become the current research trend. The most co-cited literature was published in Sports Medicine. The strongest citation burst was related to electroencephalogram (EEG) event-related potential and spectral power analysis., Conclusion: Publication information of related literature on the objective assessment of cognitive fatigue from 2007 to 2024 was summarized, including country and institute of origin, authors, and published journal, offering the current hotspots and novel directions in this field., 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 Han, Bai, Zhang, Liu, Yang, Shang, Song, Su, Hao, Feng, Li and Wang.)

Understanding the genetic causes of obesity permits anticipatory guidance and targeted treatments. Children with hyperphagia and severe early-onset obesity should receive genetic testing for rare monogenic and syndromic disorders caused by pathogenic variants involving a single gene or single chromosomal region. Gene panels covering the leptin pathway, the key regulator of energy balance, are becoming more widely available and at lower cost. Polygenic obesity is much more common and involves multiple genes throughout the genome, although the overlap in genes for rare and common disorders suggests a spectrum of severity and the potential of shared precision medicine approaches for treatment., Competing Interests: Disclosures J.C. Han is a clinical trial investigator for multisite research studies sponsored by Rhythm Pharmaceuticals. The remaining authors have no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The first type II intramolecular [3 + 2] annulation of allenylsilane-ene has been achieved, enabling diastereoselective and efficient construction of synthetically challenging bridged five-membered ring systems such as bicyclo[3.2.1]. This mild and direct process shows a broad substrate scope and is highly stereospecific. Particularly, this work represents the first stereoselective method for the direct synthesis of bicyclo[3.2.1] ring systems from acyclic precursors. Additionally, the first asymmetric total syntheses of (+)- and (-)-strepsesquitriol, and the efficient formation of the synthetically challenging tetracyclic core of pierisjaponol D are achieved by this type II [3 + 2] annulation reaction.

Three bacterial strains, 1AS14I T , 1AS12I and 6AS6, isolated from root nodules of Acacia saligna , were characterized using a polyphasic approach. Phylogenetic analysis based on rrs sequences placed all three strains within the Rhizobium leguminosarum complex. Further phylogeny, based on 1 756 bp sequences of four concatenated housekeeping genes ( recA , atpD , glnII and gyrB ), revealed their distinction from known rhizobia species of the R. leguminosarum complex (Rlc), forming a distinct clade. The closest related species, identified as Rhizobium laguerreae , with a sequence identity of 96.4% based on concatenated recA - atpD - glnII - gyrB sequences. The type strain, 1AS14I T , showed average nucleotide identity (ANI) values of 94.9, 94.3 and 94.1% and DNA-DNA hybridization values of 56.1, 57.4 and 60.0% with the type strains of closest known species: R. laguerreae , Rhizobium acaciae and 'Rhizobium indicum', respectively. Phylogenomic analyses using 81 up-to-date bacteria core genes and the Type (Strain) Genome Server pipeline further supported the uniqueness of strains 1AS14I T , 1AS12I and 6AS6. The relatedness of the novel strains to NCBI unclassified Rhizobium sp. (396 genomes) and metagenome-derived genomes showed ANI values from 76.7 to 94.8% with a species-level cut-off of 96%, suggesting that strains 1AS14I, 1AS12I and 6AS6 are a distinct lineage. Additionally, differentiation of strains 1AS14I T , 1AS12I and 6AS6 from their closest phylogenetic neighbours was achieved using phenotypic, physiological and fatty acid content analyses. Based on the genomic, phenotypic and biochemical data, we propose the establishment of a novel rhizobial species, Rhizobium aouanii sp. nov., with strain 1AS14I T designated as the type strain (=DSM 113914 T =LMG 33206 T ). This study contributes to the understanding of microbial diversity in nitrogen-fixing symbioses, specifically within Acacia saligna ecosystems in Tunisia.

Background and Objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations., Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations., Results: Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R 2  = 0.466, and mean bias of 23 kcal/day., Conclusion: This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth., (© 2024 World Obesity Federation.)

Objectives: Delirium is a serious complication of cardiac surgery and a common clinical problem. The study aimed to identify the incidence, risk factors, and outcomes of delirium in older patients (≥ 65 years) with first-ever acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI)., Methods: A retrospective cohort study was performed in a hospital in northern China. A total of 1033 older patients with first-ever AMI who underwent PCI between January 2018 and April 2021 were screened for delirium using the CAM-ICU method. Clinical and laboratory data were collected., Results: A total of 134 (12.97%) patients were diagnosed with delirium. Patients with delirium were older. The most common concomitant diseases were cardiac arrest, chronic renal failure, and a history of coronary artery bypass graft (CABG). Delirious patients experienced more times of mechanical ventilation, more intra-aortic balloon pump (IABP) support, high postoperative immediate pain score (VAS), more non-bedside cardiac rehabilitation, and longer total length of stay and cardiac care unit (CCU) time. Multivariable logistic regression showed that age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently associated with delirium. Delirium was an independent predictor of prolonged CCU stay, total length of stay, and 1‑year mortality., Conclusion: Age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently closely related to delirium in older patients with first-ever AMI who underwent PCI. Delirium was associated with a higher 1‑year all-cause mortality., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi-omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, n = 5), exfoliation glaucoma (XFG, n = 4), primary open-angle glaucoma (POAG, n = 11), and cataracts (control group, n = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data-independent acquisition and data-dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L-phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L-phenylalanine or C3, APOD, and L-valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma., (© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P < 0.001); the minimum residual neuroretinal rim width showed a more pronounced difference (29.7 ± 8.2% vs 7.1 ± 3.9%, P < 0.001). The changes distributed predominantly towards the nasal direction in chON, contrasting the changes to the arcuate fibers in glaucoma. In conclusion, our results provide the first longitudinal evidence of true pathological cupping in chONcompared to photographically disease-free baseline. The marked difference in the residual minimum rim width reaffirms the importance of rim obliteration in the differential diagnosis between the two diseases., (© 2024. The Author(s).)

2D Bi 2 O 2 Se has recently garnered significant attention in the electronics and optoelectronics fields due to its remarkable photosensitivity, broad spectral absorption, and excellent long-term environmental stability. However, the development of integrated Bi 2 O 2 Se photodetector with high performance and low-power consumption is limited by material synthesis method and the inherent high carrier concentration of Bi 2 O 2 Se. Here, a type-I heterojunction is presented, comprising 2D Bi 2 O 2 Se and lead-free bismuth perovskite CsBi 3 I 10 , for fast response and broadband detection. Through effective charge transfer and strong coupling effect at the interfaces of Bi 2 O 2 Se and CsBi 3 I 10 , the response time is accelerated to 4.1 µs, and the detection range is expanded from ultraviolet to near-infrared spectral regions (365-1500 nm). The as-fabricated photodetector exhibits a responsivity of 48.63 AW -1 and a detectivity of 1.22×10 12 Jones at 808 nm. Moreover, efficient modulation of the dominant photocurrent generation mechanism from photoconductive to photogating effect leads to sensitive response exceeding 10 3 AW -1 for heterojunction-based photo field effect transistor (photo-FETs). Utilizing the large-scale growth of both Bi 2 O 2 Se and CsBi 3 I 10 , the as-fabricated integrated photodetector array demonstrates outstanding homogeneity and stability of photo-response performance. The proposed 2D Bi 2 O 2 Se/CsBi 3 I 10 perovskite heterojunction holds promising prospects for the future-generation photodetector arrays and integrated optoelectronic systems., (© 2023 Wiley‐VCH GmbH.)

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases., (© The Author(s) 2024. Published by Oxford University Press.)

As one of the most rapidly developing cities in China, Shenzhen grapples with an increasing challenge in managing water resources due to escalating conflicts with its soaring water demand. This study established a system dynamics (SD) model based on a causal loop diagram to explore the intricate interconnections within the urban water resources system. Through simulating water supply and demand in Shenzhen from 2021 to 2035, the model identified key sensitive factors and examined various utilization scenarios for multiple water resources. Results indicated that water scarcity posed a significant obstacle to Shenzhen's development. To tackle this challenge, several effective measures should be implemented, including enhancing water conservation capabilities, developing seawater resources, promoting water reuse, optimizing the economic structure, and managing population growth. Prioritizing water conservation efforts and maximizing the utilization of seawater resources were regarded as the most impactful strategies in alleviating the water crisis. Furthermore, the relationship between water conservation capabilities and seawater utilization scale was analyzed using the SD model, contributing to the development of a comprehensive water resources management strategy. The findings from this study would provide insights into robust methods for allocating water resources, thereby enhancing sustainable water management strategies applicable to regions facing similar challenges., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coastal shallow waters are highly vulnerable to pollution, often leading to the development of intricate eutrophication zones. However, accurately determining these areas poses a significant challenge due to the complex interplay of estuarine hydrodynamics and nutrient transformation. To address such issue, a novel method was proposed to identify high-nutrient zones through calculating the continuous zonation of released tracers when their instantaneous concentrations declined to 1/e of their initial values. The method was well tested using idealized estuary models with varying shape parameters, water depths and river discharges. The results consistently revealed that the boundaries of high-nutrient zones fell within the mixed zone, characterized by salinity levels of 10- 20 psu. In Shenzhen Bay, a typical shallow bay, distinct differences were observed in the concentrations of dissolved inorganic nitrogen (DIN) and PO 4 3- . Both the 20 psu isohaline and the proposed method effectively identified the partition boundary of high DIN and PO 4 3- in 2001-2010, but only the newly proposed method demonstrated accuracy in delineating the actual high-nutrient zone during the continuous nutrient reduction period from 2010 to 2020. This study provides a practical and feasible approach that can serve as an auxiliary decision-making tool for managing estuarine water environments, and it has potential to facilitate the implementation of timely and effective measures for pollution control., 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 B.V. All rights reserved.)

We aimed to investigate the age-related glaucoma progression rates in myopic normal tension glaucoma (NTG). In this long-term retrospective cohort (7.2 ± 3.5 years), we grouped patients based on their age at initial presentation: group A (age < 30 years, 60 eyes), group B (30 ≤ age < 40, 66 eyes), and group C (40 ≤ age < 50 years, 63 eyes). We used a linear mixed-effects model to estimate retinal nerve fiber layer (RNFL) defect width enlargement rates. Group A showed a significantly faster rate of RNFL defect progression (3.01 ± 1.74°/year) than those of groups B and C (2.05 ± 1.55°/year and 2.06 ± 1.29°/year, P = 0.004 and 0.002). The difference was more marked when calculated for the first 10 years of follow-up in group A, B, and C (3.95 ± 2.70°/year, 2.39 ± 1.64°/year, and 1.98 ± 1.31°/year), and between the periods of age < 30 years, 30 ≤ age < 40 years, and 40 ≤ age < 50 years within group A. This is the first evidence of rapid glaucoma progression in the young adulthood and stabilization in older age in myopic NTG. Clinicians should consider the potentially aggressive course of glaucoma, especially in younger patients with myopic NTG, in contrast to the general slow progression in adulthood., (© 2024. The Author(s).)

Multi-scale models of cardiac energetics are becoming crucial in better understanding the prevalent chronic diseases operating at the intersection of metabolic and cardiovascular dysfunction. Computationally efficient models of cardiac cross-bridge kinetics that are sensitive to changes in metabolite concentrations are necessary to simulate the effects of disease-induced changes in cellular metabolic state on cardiac mechanics across disparate spatial scales. While these models do currently exist, deeper analysis of how the modelling of metabolite effects and the assignment of strain dependence within the cross-bridge cycle affect the properties of the model is required. In this study, model linearisation techniques were used to simulate and interrogate the complex modulus of an ODE-based model of cross-bridge kinetics. Active complex moduli were measured from permeabilised rat cardiac trabeculae under five different metabolite conditions with varying ATP and P i concentrations. Sensitivity to metabolites was incorporated into an existing three-state cross-bridge model using either a direct dependence or a rapid equilibrium approach. Combining the two metabolite binding methods with all possible locations of strain dependence within the cross-bridge cycle produced 64 permutations of the cross-bridge model. Using linear model analysis, these models were systematically explored to determine the effects of metabolite binding and their interaction with strain dependence on the frequency response of cardiac muscle. The results showed that the experimentally observed effects of ATP and P i concentrations on the cardiac complex modulus could be attributed to their regulation of cross-bridge detachment rates. Analysis of the cross-bridge models revealed a mechanistic basis for the biochemical schemes which place P i release following cross-bridge formation and ATP binding prior to cross-bridge detachment. In addition, placing strain dependence on the reverse rate of the cross-bridge power stroke produced the model which most closely matched the experimental data. From these analyses, a well-justified metabolite-sensitive model of rat cardiac cross-bridge kinetics is presented which is suitable for parameterisation with other data sets and integration with multi-scale cardiac models., 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 Musgrave, Han, Ward, Taberner and Tran.)

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al 3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery., Methods: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables., Results: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001)., Conclusions: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The environmental issue of lead (Pb), cadmium (Cd), and tetracycline (TC) contamination in cereal crops has become a growing concern worldwide. An in-depth understanding of this issue would be of importance to promote effective management strategies for heavy metals and antibiotics worldwide. The present study was conducted to assess the toxic effects of heavy metals (Cd, Pb) and antibiotics (TC) on Triticum aestivum (T. aestivum, common wheat) based on studies conducted in the past 22 years. Data pertaining to the growth and development of T. aestivum were extracted and analyzed from 89 publications spanning from 2000 to 2022. Our results showed that Pb, Cd and TC significantly reduced growth and development by 11 %, 9 %, and 5 %, respectively. Additionally, significant accumulation of Cd (42 %) and Pb (17 %) was observed in T. aestivum samples, although there was little change in TC accumulation, which showed limited absorption, accumulation, and translocation of TC in wheat plants. Pb had the greatest impact on the yield of T. aestivum, followed by Cd, while TC had no apparent effect. Furthermore, exposure to Cd, Pb and TC reduced the photosynthetic rate due to chlorophyll reduction, with Cd having the most pronounced effect (58 %), followed by Pb (37 %) and TC (8 %). Cd exposure also significantly enhanced gaseous exchange (37 %) compared to TC and Pb, which reduced gaseous exchange by 4 % and 10 %, respectively. However, the treatments with TC (>50-100 mgL -1 ), Pb (>1000-2000 mg L -1 ) and Cd (>500-1000 mg L -1 ) increased the defense system of T. aestivum samples by 38 %, 15 %, and 11 %, respectively. The obtained findings have significant implications for risk assessment, pollution prevention, and remediation strategies to address soil contamination from Pb, Cd and TC in farmland., 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 B.V. All rights reserved.)

Myofilament calcium (Ca 2+ ) sensitivity is one of several mechanisms by which force production of cardiac muscle is modulated to meet the ever-changing demands placed on the heart. Compromised Ca 2+ sensitivity is associated with pathologies, which makes it a parameter of interest for researchers. Ca 2+ Sensitivity is the ratio of the association and dissociation rates between troponin C (TnC) and Ca 2+ . As it is not currently possible to measure these rates in tissue preparations directly, methods have been developed to infer myofilament sensitivity, typically using some combination of force and Ca 2+ measurements. The current gold-standard approach constructs a steady-state force-Ca 2+ relation by exposing permeabilised muscle samples to a range of Ca 2+ concentrations and uses the half-maximal concentration as a proxy for sensitivity. While a valuable method for steady-state investigations, the permeabilisation process makes the method unsuitable when examining dynamic, i.e., twitch-to-twitch, changes in myofilament sensitivity. The ability of the heart to transiently adapt to changes in load is an important consideration when evaluating the impact of disease states. Alternative methods have been proffered, including force-Ca 2+ phase loops, potassium contracture, hybrid experimental-modelling and conformation-based fluorophore approaches. This review provides an overview of the mechanisms underlying myofilament Ca 2+ sensitivity, summarises existing methods, and explores, with modelling, whether any of them are suited to investigating dynamic changes in sensitivity. We conclude that a method that equips researchers to investigate the transient change of myofilament Ca 2+ sensitivity is still needed. We propose that such a method will involve simultaneous measurements of cytosolic Ca 2+ and TnC activation in actively twitching muscle and a biophysical model to interpret these data., 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 © 2023 Dowrick, Taberner, Han and Tran.)

Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region., Competing Interests: Disclosure J.C. Han is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals. A.M. Haqq is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals, Levo Therapeutics, and Eli Lilly. She has received grants from the Weston Family Microbiome Initiative and Canadian Institutes of Health Research, Canada, payment as a speaker for Pfizer Canada, and is a member of advisory boards for Pfizer, Rhythm Pharmaceuticals, and Novo Nordisk Canada. The remaining authors have no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of intramedullary nail fixation (IMN) and minimally invasive percutaneous plate internal fixation (MIPPO) techniques on tibiofibular fractures and their effect on platelet activation and serum transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2)., Methods: Total of 105 patients with tibiofibular fractures from February 2019 to February 2020 were selected and divided into 53 cases in the MIPPO group and 52 cases in the IMN group. There were 29 males and 24 females with an average age of (41.74±6.05) years old in MIPPO group;in IMN group, 31 males and 21 females with an average age of (40.59±5.26) years old. The perioperative surgical indexes, postoperative complications, ankle function recovery at 12 months postoperatively, platelet activation indexes at 3 and 7 days preoperatively and postoperatively, and serum TGF-β1 and BMP-2 levels at 4 and 8 weeks preoperatively and postoperatively were compared between the two groups., Results: The operating time and fracture healing time in the MIPPO group were shorter than those in the IMN group( P <0.05); Compared with the preoperative period, the levels of GMP-140, PAC-1, CD63, and CD61 increased in both groups at 3 and 7 days after surgery, but were lower in the MIPPO group than in the IMN group( P <0.05);the levels of serum TGF-β1 and BMP-2 increased in both groups at 4 and 8 weeks after surgery compared with the preoperative period, and the postoperative complication rate in the MIPPO group was lower than that in the IMN group( P <0.05);the difference was not statistically significant in the excellent rate of ankle function recovery at 12 months follow-up after surgery between two groups( P >0.05)., Conclusion: Both intramedullary nail fixation and MIPO technique for treatment of tibia and fibula fractures can improve ankle joint function, but the latter has the advantages of short operation time, fast fracture healing, fewer complications, and light platelet activation. Serum TGF-β1, BMP-2 level improves quickly.

Isolated cardiac tissues allow a direct assessment of cardiac muscle function and enable precise control of experimental loading conditions. However, current experimental methods do not expose isolated tissues to the same contraction pattern and cardiovascular loads naturally experienced by the heart. In this study, we implement a computational model of systemic-pulmonary impedance that is solved in real time and imposed on contracting isolated rat muscle tissues. This systemic-pulmonary model represents the cardiovascular system as a lumped-parameter, closed-loop circuit. The tissues performed force-length work-loop contractions where the model output informed both the shortening and restretch phases of each work-loop. We compared the muscle mechanics and energetics associated with work-loops driven by the systemic-pulmonary model with that of a model-based loading method that only accounts for shortening. We obtained results that show simultaneous changes of afterload and preload or end-diastolic length of the muscle, as compared with the static, user-defined preload as in the conventional loading method. This feature allows assessment of muscle work output, heat output, and efficiency of contraction as functions of end-diastolic length. The results reveal the behavior of cardiac muscle as a pump source to achieve load-dependent work and efficiency outputs over a wider range of loads. This study offers potential applications of the model to investigate cardiac muscle response to hemodynamic coupling between systemic and pulmonary circulations in an in vitro setting. NEW & NOTEWORTHY We present the use of a "closed-loop" model of systemic and pulmonary circulations to apply, for the first time, real-time model-calculated preload and afterload to isolated cardiac muscle preparations. This method extends current experimental protocols where only afterload has been considered. The extension to include preload provides the opportunity to investigate ventricular muscle response to hemodynamic coupling and as a pump source across a wider range of cardiovascular loads.

Objective: Alström syndrome (AS) is a rare multisystem disorder of which early onset childhood obesity is a cardinal feature. Like humans with AS, animal models with Alms1 loss-of-function mutations develop obesity, supporting the notion that ALMS1 is required for the regulatory control of energy balance across species. This study aimed to determine which component(s) of energy balance are reliant on ALMS1., Methods: Comprehensive energy balance phenotyping was performed on Alms1 tvrm102 mice at both 8 and 18 weeks of age., Results: It was found that adiposity gains occurred early and rapidly in Alms1 tvrm102 male mice but much later in females. Rapid increases in body fat in males were due to a marked reduction in energy expenditure (EE) during early life and not due to any genotype-specific increases in energy intake under chow conditions. Energy intake did increase in a genotype-specific manner when mice were provided a high-fat diet, exacerbating the effects of reduced EE on obesity progression. The EE deficit observed in male Alms1 tvrm102 mice did not persist as mice aged., Conclusions: Either loss of ALMS1 causes a developmental delay in the mechanisms controlling early life EE or activation of compensatory mechanisms occurs after obesity is established in AS. Future studies will determine how ALMS1 modulates EE and how sex moderates this process., (© 2023 The Obesity Society.)

Background/aims: To identify the spatial relationship between disc haemorrhage (DH) on the fovea-disc axis and retinal nerve fibre layer (RNFL) defect in the papillomacular bundle (PMB) using ancillary PanoMap optical coherence tomography (OCT)., Methods: We investigated the presence and progression of spatially corresponding PMB defects in glaucomatous eyes with temporally located DH on the fovea-disc axis (FoDi-DH). We identified PMB defects using ancillary PanoMap OCT with guided progression analysis, in addition to red-free photographs., Results: We studied 36 eyes of 35 glaucoma patients with FoDi-DH, pre-existing PMB defects were observed in 18 eyes (50.0%) at the time and location of the initial FoDi-DH occurrence, 14 (38.9%) of which progressed during the follow-up period. New development of PMB defects occurred in 15 (41.7%) of 18 eyes without pre-existing PMB defects. Overall, FoDi-DH was associated with PMB defects in 33 (91.7%) eyes at locations spatially overlapping the PMB defect. Red-free photography and OCT were complementary in detecting PMB defects and progression. Among 47 cases, 20 were concordant, while 10 and 17 were detected only in photography and OCT, respectively. The central visual field defect increased significantly throughout the follow-up period (p=0.006)., Conclusion: Most FoDi-DH cases were related to the presence and progression of glaucomatous PMB defects at locations spatially overlapping the defect. OCT helped clarify changes in PMB defects detected by red-free photograph and the detection of photo-negative PMB defects as well. Similar to inferotemporal and superotemporal-direction DH, temporal DH on the PMB may be an indicator of ongoing RNFL damage that deserves close attention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To study deep optic nerve head (ONH) morphology in tilted disc syndrome (TDS) and identify factors associated with retinal nerve fiber layer (RNFL) defect., Methods: In patients with TDS, we evaluated the optic disc shape using the Bruch's membrane opening (BMO)-anterior scleral canal opening (ASCO) offset and measured the border tissue (BT) length, depth, and angle in the direction of the tilt, using radial ONH optical coherence tomography (OCT). We compared the parameters between the TDS groups with and without RNFL defects., Results: Twenty-one eyes had no glaucomatous RNFL defect, and 38 eyes had a glaucomatous RNFL defect. The group with RNFL defects had a higher baseline IOP, larger tilt axis of BMO-ASCO optic disc margin (76.4° ± 14.5° vs. 87.9° ± 15.4°, P = 0.012), larger BMO-lamina cribrosa insertion (LCI) angle (25.6° ± 9.3° vs. 43.6° ± 15.2°, P < 0.001), and more lamina cribrosa (LC) defects (4.3% vs. 30.6%, P = 0.028) than without RNFL defects. The tilt axis and BMO-LCI angle were significant factors after adjusting for baseline IOP and LC defect. The BMO-LCI angle had excellent diagnostic power for glaucomatous RNFL defect in TDS, similar to the visual field mean deviation., Conclusions: OCT-based large deep ONH BT angle and tilt axis were factors associated with the presence of RNFL defects in TDS. The results suggest a mechanism of RNFL defect associated with structural ONH deformation. Further investigations are warranted to understand the role of ONH structures in a general population with and without optic disc tilt.

In the excitation of muscle contraction, calcium ions interact with transmembrane transporters. This process is accompanied by energy consumption and heat liberation. To quantify this activation energy or heat in the heart or cardiac muscle, two non-pharmacological approaches can be used. In one approach using the "pressure-volume area" concept, the same estimate of activation energy is obtained regardless of the mode of contraction (either isovolumic/isometric or ejecting/shortening). In the other approach, an accurate estimate of activation energy is obtained only when the muscle contracts isometrically. If the contraction involves muscle shortening, then an additional component of heat associated with shortening is liberated, over and above that of activation. The present study thus examines the reconcilability of the two approaches by performing experiments on isolated muscles measuring contractile force and heat output. A framework was devised from the experimental data to allow us to replicate several mechanoenergetics results gleaned from the literature. From these replications, we conclude that the choice of initial muscle length (or ventricular volume) underlies the divergence of the two approaches in the estimation of activation energy when the mode of contraction involves shortening (ejection). At low initial muscle lengths, the heat of shortening is relatively small, which can lead to the misconception that activation energy is contraction mode independent. In fact, because cardiac muscle liberates heat of shortening when allowed to shorten, estimation of activation heat must be performed only under isometric (isovolumic) contractions. We thus recommend caution when estimating activation energy using the "pressure-volume area" concept., 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 © 2023 Han, Pham, Taberner, Loiselle and Tran.)

The core endophytes of plants are regarded as promising resources in future agroecosystems. How they affect the assembly of rice-related bacterial communities after early inoculation remains unclear. Here, we examined bacterial communities across 148 samples, including bulk and rhizosphere soils, sterilized roots, stems, and seeds at the seedling, tillering, booting, and maturity stages. Tissue cultured rice seedlings were inoculated with Xathomonas sacchari JR3-14, a core endophytic bacterium of rice seeds, before transplanting. The results revealed that α-diversity indices were significantly enhanced in the root and stem endosphere at the seedling stage. β-diversity was altered at most plant developmental stages, except for the root and stem at the booting stage. Network complexity consequently increased in the root and stem across rice growth stages, other than the stem endosphere at the booting stage. Four abundant beneficial bacterial taxa, Bacillus , Azospira , Azospirillum , and Arthrobacter , were co-enriched during the early growth stage. Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model analysis revealed a higher relative contribution of drift and other eco-evolutionary processes mainly in root compartments across all growth stages, but the opposite pattern was observed in stem compartments. IMPORTANCE Endophytic bacteria are regarded as promising environmentally friendly resources to promote plant growth and plant health. Some of microbes from the seed are able to be carried over to next generation, and contribute to the plant's ability to adapt to new environments. However, the effects of early inoculation with core microbes on the assembly of the plant microbiome are still unclear. In our study, we demonstrate that early inoculation of the rice seed core endophytic bacterium Xanthomonas sacchari could alter community diversity, enhance complexity degree of network structure at most the growth stages, and enrich beneficial bacteria at the seedling stage of rice. We further analyzed the evolutionary processes caused by the early inoculation. Our results highlight the new possibilities for research and application of sustainable agriculture by considering the contribution of seed endophytes in crop production and breeding.

Purpose: To investigate the differences in peripapillary vessel density (VD) between compressive optic neuropathy (CON) and normal-tension glaucoma (NTG)., Methods: We compared patients with chronic CON and NTG, particularly after strictly controlling the mean extent of macular damage by the area of the ganglion cell-inner plexiform layer (GCIPL) loss in optical coherence tomography (OCT). We compared retinal nerve fiber layer (RNFL) and GCIPL thickness from OCT and peripapillary and macular VD from OCT angiography (OCTA) between the CON and NTG groups., Results: From the initial 184 patients with CON and 443 patients with OAG, we included 41 patients with CON (57 eyes) and 64 patients with NTG (75 eyes) with a comparable extent of macular GCIPL thinning. Under similar mean macular involvement, the peripapillary VD was significantly lower in the CON group than in the NTG group after considering the effects of age, spherical equivalent, visual field sensitivity, peripapillary RNFL (pRNFL) thickness, GCIPL thickness, and image quality scores (P < 0.001). Marked loss of VD in the temporal and nasal sectors in CON was notable, attributing to the significantly lower peripapillary VD compared to NTG., Conclusions: Patients with CON had a significantly lower peripapillary VD than those with NTG under similar mean degrees of pRNFL thickness and GCIPL damage. Our results reveal the potential utility of OCTA VD besides OCT pRNFL thickness, in relation to different topographic patterns of pRNFL loss, and possible differences in the pathogenesis of microvascular compromise between CON and NTG.

The removal of diverse refractory organics from complex industrial wastewater continues to be a challenge. Although biological treatments are commonly employed, only partial degradation and increasing emergence of nitrogenous compounds, i.e., nitrate (NO 3 ) and nitrite (NO 2 ) would pose severe toxicity to the intact microbes. Herein, an efficient biocatalytic microbial ecosystem (BCME) was designed over a porous bio-carrier made of a functional polyurethane sponge (FPUS). The BCME comprised a unique set of organisms (RODMs) with novel metabolism, efficiently degrading highly-concentrated aromatics. Strategic enzyme immobilization was utilized to introduce in-situ production and aggregation of the oxidation and reduction enzymes (In-PAOREs) onto the FPUS, thereby ensuing sustained functions of the RODMs community. The developed FPUS@RODMs@In-PAOREs system was found to enhance the refractory organics removal rate to 4 kg/m 3 /day, and it would be attributed to the enzymatic catalysis of refractory organics (2000 mg/L) accompanied by the removal of COD (1200 mg/L) and nitrogenous compounds (200 mg/L). Besides, the fluctuating concentration of extra polymeric substances (EPS) played a dual role through enhancing adhesion, promoting the development of a functional microbial ecosystem, and creating an EPS gradient within the FPUS bio-carrier. This differential distribution of enzymes was established to significantly boost biocatalysis activity reaching 400 U/g VSS., 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 B.V. All rights reserved.)