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Polycyclic aromatic hydrocarbons (PAHs) present in oily sludge generated by the petroleum and petrochemical industries have emerged as a prominent concern within the realm of environmental conservation. The precise determination of PAHs holds immense significance in both petroleum geochemistry and environmental protection. In this study, a combination of surface-enhanced Raman spectroscopy (SERS) and solid-liquid extraction was employed for the screening of PAHs in oily sludge. Methanol was utilized as the extraction solvent for PAHs, while nanosilver-silicon coupling substrates were employed for their detection. The SERS spectrum was acquired using a portable Raman spectrometer. The nano silver-silicon coupling substrate exhibits excellent uniformity, with relative standard deviations (RSDs) of Phenanthrene, Fluoranthrene, Fluorene and Naphthalene (Phe, Flt, Flu and Nap) being 2.8%, 1.08%, 1.41%, and 5.44% respectively. Moreover, the limits of detection (LODs) achieved remarkable values of 0.542 μg/g, 0.342 μg/g, 0.541 μg/g, and 5.132 μg/g. The quantitative analysis of PAHs in oily sludge was investigated using SERS technology combined with partial least squares (PLS). The optimal PLS calibration model was optimized by combining spectral preprocessing methods and using the SiPLS (Synergy interval partial least squares)-VIP (Variable Importance in Projection) hybrid variable selection strategy. The prediction performance of the D1st (First derivative)-WT (Wavelet transform)-SiPLS-VIP-PLS model was deemed satisfactory, as evidenced by high R 2 P values of 0.9851, 0.9917, and 0.9925 for Phe, Flt, and Flu respectively; additionally, the corresponding MREP values were found to be 0.0580, 0.0668, and 0.0669 respectively. However, for Nap analysis, the D1st-WT-PLS model proved to be a better calibration model with an R 2 P value of 0.9864 and an MREP (Mean relative error of prediction) value of 0.0713. In summary, SERS technology combined with PLS based on different spectral pretreatment methods and mixed variable selection strategies is a promising method for quantitative analysis of PAHs in oily sludge, which will provide new ideas and methods for the quantitative analysis of PAHs in oily sludge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A series of novel quinazoline-derived EGFR/HER-2 dual-target inhibitors were designed and synthesized by heterocyclic-containing tail approach. The inhibitory activities against four human epidermal growth factor receptor (HER) isozymes (EGFR, HER-2, HER-3 and HER-4) of all new compounds so designed were investigated in vitro. Compound 12k was found to be the most effective and rather selective dual-target inhibitor of EGFR and HER-2 with inhibitory constant (IC 50 ) values of 6.15 and 9.78 nM, respectively, which was more potent than the clinical used agent Lapatinib (IC 50  = 8.41 and 9.41 nM). Meanwhile, almost all compounds showed excellent antiproliferative activities against four cancer cell models (A549, NCI-H1975, SK-BR-3 and MCF-7) and low damage to healthy cells. Among them, compound 12k also exhibited the most prominent antitumor activity. Moreover, the hit compound 12k could bind to EGFR and HER-2 stably in molecular docking and dynamics studies. The following wound healing assay revealed that compound 12k could inhibit the migration of SK-BR-3 cells. Further studies found that compound 12k could arrest cell cycle in the G0/G1 phase and induce SK-BR-3 cells apoptosis. Notably, compound 12k could effectively inhibit breast cancer growth with little toxicity in the SK-BR-3 cell xenograft model. Taken together, in vitro and in vivo results disclosed that compound 12k had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth., 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.)

Bacteria infections pose a serious threat to public health, and it is urgent to develop facile and accurate detection methods. To meet the important need, a potable and high-sensitive surface enhanced Raman scattering (SERS) biosensor based on aptamer recognition and catalytic hairpin assembly (CHA) signal amplification was proposed for point-of-care detection of Staphylococcus aureus (S. aureus). The SERS biosensor contains three parts: recognition probes, SERS sensing chip, and SERS tags. The feasibility of the strategy was verified by gel electrophoresis, and the one-step test route was optimized. The bacteria SERS biosensor has a good linear relationship ranging from 10 to 10 7  CFU mL -1 with high sensitivity low to 5 CFU mL -1 , and shows excellent specificity, uniformity, and repeatability on S. aureus identification and enumeration, which can distinguish S. aureus from other bacteria. The SERS biosensor shows a good recovery rate (95.73 %-109.65 %) for testing S. aureus spiked in milk, and has good practicability for detecting S. aureus infected mouse wound, which provides a facile and reliable approach for detection of trace bacteria in the 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 B.V. All rights reserved.)

The performance and stability of organic metal halide perovskite (OMHP) optoelectronic devices have been associated with ion migration. Understanding of nanoscale resolved organic cation migration mechanism would facilitate structure engineering and commercialization of OMHP. Here, we report a three-dimensional approach for in situ nanoscale infrared imaging of organic ion migration behavior in OMHPs, enabling to distinguish migrations along grain boundary and in crystal lattice. Our results reveal that organic cation migration along OMHP film surface and grain boundaries (GBs) occurs at lower biases than in crystal lattice. We visualize the transition of organic cation migration channels from GBs to volume upon increasing electric field. The temporal resolved results demonstrate the fast MA + migration kinetics at GBs, which is comparable to diffusivity of halide ions. Our findings help understand the role of organic cations in the performance of OMHP devices, and the proposed approach holds broad applicability for revealing migration mechanisms of organic ions in OMHPs based optoelectronic devices., (© 2024 Wiley-VCH GmbH.)

Many major diseases of the retina often show symptoms of lesions in the fundus of the eye. The extraction of blood vessels from retinal fundus images is essential to assist doctors. Some of the existing methods do not fully extract the detailed features of retinal images or lose some information, making it difficult to accurately segment capillaries located at the edges of the images. In this paper, we propose a multi-scale retinal vessel segmentation network (SCIE_Net) based on skip connection information enhancement. Firstly, the network processes retinal images at multiple scales to achieve network capture of features at different scales. Secondly, the feature aggregation module is proposed to aggregate the rich information of the shallow network. Further, the skip connection information enhancement module is proposed to take into account the detailed features of the shallow layer and the advanced features of the deeper network to avoid the problem of incomplete information interaction between the layers of the network. Finally, SCIE_Net achieves better vessel segmentation performance and results on the publicly available retinal image standard datasets DRIVE, CHASE_DB1, and STARE., (© 2024. International Federation for Medical and Biological Engineering.)

Plantarflexors provide propulsion during walking and receive input from both corticospinal and corticoreticulospinal tracts, which exhibit some frequency-specificity that allows potential differentiation of each tract's descending drive. Given that stroke may differentially affect each tract and impair the function of plantarflexors during walking; here, we examined this frequency-specificity and its relation to walking-specific measures during post-stroke walking. Fourteen individuals with chronic stroke walked on an instrumented treadmill at self-selected and fast walking speed (SSWS and FWS, respectively) while surface electromyography (sEMG) from soleus (SOL), lateral gastrocnemius (LG), and medial gastrocnemius (MG) and ground reaction forces (GRF) were collected. We calculated the intermuscular coherences (IMC; alpha, beta, and low-gamma bands between SOL-LG, SOL-MG, LG-MG) and propulsive impulse using sEMG and GRF, respectively. We examined the interlimb and intralimb IMC comparisons and their relationships with propulsive impulse and walking speed. Interlimb IMC comparisons revealed that beta LG-MG (SSWS) and low-gamma SOL-LG (FWS) IMCs were degraded on the paretic side. Intralimb IMC comparisons revealed that only alpha IMCs (both speeds) exhibited a statistically significant difference to random coherence. Further, alpha LG-MG IMC was positively correlated with propulsive impulse in the paretic limb (SSWS). Alpha and beta/low-gamma bands may have a differential functional role, which may be related to the frequency-specificity of the underlying descending drives. The persistence of alpha band in plantarflexors and its strong positive relationship with propulsive impulse suggests relative alteration of corticoreticulospinal tract after stroke. These findings imply the presence of frequency-specific descending drives to walking-specific muscles in chronic stroke., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

TMEM56, a gene coding a transmembrane protein, is abundantly expressed in erythroid cells. Despite this, its role in erythropoiesis has not been well characterized. In this study, we sought to clarify the function of TMEM56 in erythroid development, focusing specifically on its involvement in haem biosynthesis and cell cycle progression. To do this, we used CD34 + haematopoietic stem cells derived from umbilical cord blood and differentiated them into erythroid cells in an ex vivo model. Our results indicate that the loss of TMEM56 disrupts haem biosynthesis and impairs erythroid differentiation. Furthermore, deletion of Tmem56 in the erythroid lineage in murine models using erythropoietin receptor (EpoR)-Cre revealed defects in erythroid progenitors within the bone marrow under both normal conditions and during haemolytic anaemia. These observations underscore the regulatory role of TMEM56 in maintaining erythroid lineage homeostasis. Taken together, our results unveil a previously unrecognized function of TMEM56 in erythroid differentiation and suggest its potential as an unfounded target for therapeutic strategies in the treatment of erythropoietic disorders., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: A dosimetric evaluation is still lacking in terms of clinical target volume (CTV) omission in stage III patients treated with 4D-CT Intensity-Modulated Radiation Therapy (IMRT)., Methods: 49 stage III NSCLC patients received 4D-CT IMRT were reviewed. Target volumes and organs at risk (OARs) were re-delineated. Four IMRT plans were conducted retrospectively to deliver different prescribed dose (74 Gy-60 Gy), and with or without CTV implementation. Dose and volume histogram (DVH) parameters were collected and compared., Results: In the PTV-g 60 Gy plan (PTV-g refers to the PTV generated from the internal gross tumor volume), only 5 of 49 patients had the isodose ≥ 50 Gy line covering at least 95% of the PTV-c (PTV-c refers to the PTV generated from the internal CTV) volume. When the prescribed dose was elevated to 74 Gy to the PTV-g, 33 of 49 patients could have the isodose ≥ 50 Gy line covering at least 95% of the PTV-c volume. In terms of OARs protection, the SIB-IMRT plan showed the lowest value of V5, V20, and mean dose of lung, had the lowest V55 of esophagus, and the lowest estimated radiation doses to immune cells (EDIC). The V20, V30, and mean dose of heart was lower in the simultaneous integrated boost (SIB) IMRT (SIB-IMRT) plan than that of the PTV-c 60 Gy plan., Conclusions: CTV omission was not suitable for stage III patients when the prescribed dose to PTV-g was 60 Gy in the era of 4D-CT IMRT. CTV omission plus high dose to PTV-g (74 Gy for example) warranted further exploration. The SIB-IMRT plan had the best protection to normal tissue including lymphocytes, and might be the optimal choice., (© 2024. The Author(s).)

Controlling cyanobacterial blooms is not only an engineering and technical issue but also an optimization problem in environment management. Under budget constraints, a novel simulation-based optimization model for cyanobacterial control is constructed in this study. The simulation model is used for simulating cyanobacteria growth and diffusion processes. The optimization model is utilized to determine the optimal search and treatment path. Through the interactive coupling of simulation modeling and resource allocation optimization, this research provides decision-makers with new operational guidelines for cyanobacterial control. Our test results demonstrate that the initial invasion frequency has a greater economic impact than invasion abundance. The nearby cells to the initial invasion are affected first, and then the influence radiates outward in a diffusion pattern. Using a slow search speed and a treatment frequency of every 10 days can achieve the lowest possible economic losses in most test scenarios. Moreover, we also find that the optimal search and treatment paths revolve around the initial invasion location. This study is a typical interdisciplinary research, which can assist water resource managers in making more accurate decisions regarding cyanobacteria removal paths, removal frequencies, and treatment speeds., 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.)

As a continuation of our efforts to develop new agrochemicals with typical architecture and efficient bioactivity from plant natural products, natural neolignan honokiol was used as a lead compound to prepare novel analogs bearing the core 2-aminobenzoxazole scaffold. Their insecticidal potency against two representative agricultural pests, Plutella xylostella Linnaeus and Mythimna separata (Walker), were evaluated in vivo. The pesticide bioassay results revealed that compounds 7″a , 9 , 10d , and 10j exhibited prominent larvicidal activity against the larvae of P. xylostella (LC 50 = 7.95, 11.85, 15.51, and 12.06 μg/mL, respectively), superior to the precursor honokiol (LC 50 = 43.35 μg/mL) and two botanical insecticides, toosendanin (LC 50 = 26.20 μg/mL) and rotenone (LC 50 = 23.65 μg/mL). Compounds 7d , 10d , and 10j displayed a more pronounced nonchoice antifeedant effect (AFC 50 = 9.48, 9.14, and 12.41 μg/mL, respectively) than honokiol (AFC 50 = 54.81 μg/mL) on P. xylostella . Moreover, compounds 7b , 7″a , 9 , 10d , 10f , and 10j showed better growth inhibitory activity against M. separata (LC 50 = 0.36, 0.34, 0.28, 0.16, 0.26, and 0.11 mg/mL, respectively) than honokiol, toosendanin, and rotenone (LC 50 = 1.48, 0.53, and 0.46 mg/mL, respectively). A potted plant assay under greenhouse conditions illustrated that compounds 10d and 10j continued to provide good control efficacy against P. xylostella and an apparent protective effect on plants. Further cytotoxicity assay revealed that the aforementioned potent compounds showed relatively moderate toxicity and a good safety profile for non-target mammalian cells. Overall, the current work provides valuable insight into the agrochemical innovation of honokiol-derived analogs for use as natural-inspired pesticides in agricultural pest management.

Performing classification on high-dimensional data poses a significant challenge due to the huge search space. Moreover, complex feature interactions introduce an additional obstacle. The problems can be addressed by using feature selection to select relevant features or feature construction to construct a small set of high-level features. However, performing feature selection or feature construction only might make the feature set suboptimal. To remedy this problem, this study investigates the use of genetic programming for simultaneous feature selection and feature construction in addressing different classification tasks. The proposed approach is tested on 16 datasets and compared with seven methods including both feature selection and feature constructions techniques. The results show that the obtained feature sets with the constructed and/or selected features can significantly increase the classification accuracy and reduce the dimensionality of the datasets. Further analysis reveals the complementarity of the obtained features leading to the promising classification performance of the proposed method., (© 2024 Massachusetts Institute of Technology.)

Glioblastoma organoids (GBOs) serve as a powerful and reliable tool to study glioblastoma stem cells (GSCs) and glioblastoma (GBM). GBOs can be derived from different materials using different methods. To identify the predominant generation methods and the most applications of GBOs, we searched four databases (PubMed, Embase, Web of Science, and Wiley Online Laboratory) from August 2021 to August 2023. After screening, 42 out of 295 articles were included and analyzed. GBOs in these articles were generated using only one material, such as tumor tissues, tumor cells, and gene-edited multifunctional stem cells, or simultaneously using two materials, such as tumor cells and normal organoids. Methodologically, direct cultivation of GBM cells or tissues was the most commonly used method to generate GBOs. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were the frequently used multifunctional stem cells to generate GBOs by simultaneously silencing P53, NF1, and PTEN using CRISPR/Cas9. In terms of applications, GBOs generated by direct cultivation of GBM tissue had the most applications, including molecular mechanisms, therapy, and culture technique. This review provides a theoretical reference for selecting an appropriate method to generate GBOs when studying GSCs and GBM., (© 2024. The Author(s).)

Constructing highly efficient electrocatalysts is vital to enhance oxygen evolution reaction (OER) performance at industrially relevant current densities. Herein, three-phase coupled Ni 3 S 2 /r-NiS/h-NiS composites are grown in situ on Ni foam (NNSN/NF) via a one-step solvothermal approach. The as-prepared composites need overpotentials of only 377 mV, 451 mV and 476 mV at 1000 mA cm -2 for the OER in alkaline freshwater, simulated seawater and seawater, respectively. In addition, the optimized catalyst exhibited long-term durability at 300 mA cm -2 . Our work clarifies designing and preparing cost-effective Ni-based sulfide electrocatalysts for the OER in alkaline freshwater/simulated seawater/seawater under industrially relevant current densities.

For the first time, the dominant magnetoelectric activity of ZIF-67-derived carbonaceous microparticles embedded with Co nanoparticles and distinctive magnetothermal effect of MIL-88B-derived Fe 3 O 4 nanocubes decorated on carbonaceous microrods, respectively, were explored to be controlled by the structure of the MOF-derived electrically conductive carbonaceous matrix and metal nanoparticles.

Introduction: In individuals with patellofemoral pain (PFP), addressing increased knee valgus during weight-bearing activities typically involves strengthening weak hip muscles. However, recent literature highlights the role of altered descending central control in abnormal movements associated with PFP. While transcranial direct current stimulation (tDCS) has demonstrated the capacity to enhance neuroplasticity, its application targeting the corticomotor function of gluteal muscles in PFP remains unexplored. This study aimed to investigate the effects of combining bimodal tDCS with exercise on frontal plane kinematics in individuals with PFP. The hypothesis was that bimodal tDCS, specifically targeting the corticomotor function of the gluteal muscles, would augment the effectiveness of exercise interventions in improving frontal plane kinematics compared to sham stimulation., Methods: Ten participants with PFP participated in two sessions involving either bimodal tDCS or sham stimulation, concurrently with hip strengthening exercises. Weight-bearing tasks, including single leg squat, single leg landing, single leg hopping, forward step-down, and lateral step-down, were performed and recorded before and after each session. Pain visual analog scale (VAS) scores were also documented. A one-way ANOVA with repeated measures was employed to compare kinematics, while a Friedman test was used to compare VAS across the three conditions (pre-test, post-tDCS, and post-Sham)., Results: We observed no significant differences in trunk lean angle, hip and knee frontal plane projection angles, or dynamic valgus index among the three conditions during the five weight-bearing tasks. VAS scores did not differ across the three conditions., Discussion and Conclusion: A single session of tDCS did not demonstrate immediate efficacy in enhancing frontal plane kinematics or relieving pain in individuals with PFP. Considering observed positive outcomes in other neurological and orthopedic populations with multi-session tDCS applications, suggesting potential cumulative effects, further research is essential to explore the effects of multi-session tDCS on weight-bearing movement and underlying neurophysiology in individuals with PFP., 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 Ho, Wallace, Aquino, Broadwell, Whimple and Liang.)

Objective: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms., Methods: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-β 1 (TGF-β 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-β 1, TGF-β 1+10% DMS, TGF-β 1+10% DMS+miR-29b-2-5p inhibitor, TGF-β 1+10% DMS+inhibitor negative control, TGF-β 1+10% DMS+miR-29b-2-5p mimic and TGF-β 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA., Results: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01)., Conclusions: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Xanthates, common mining flotation reagents, strongly bind thiophilic metals such as copper (Cu), lead (Pb), cadmium (Cd), and zinc (Zn) and consequentially change their bioavailability and mobility upon their discharge into the environment. However, accurate quantification of the metal-xanthate complexes has remained elusive. This study develops a novel and robust method that realizes the accurate quantification of the metal-xanthate complexes resulted from single and multiple reactions of three typical xanthates (ethyl, isopropyl, and butyl xanthates) and four thiophilic metals (Cu, Pb, Cd, and Zn) in water samples. This method uses sulfur (S 2- ) dissociation, followed by tandem solid phase extraction of C 18 + PWAX and subsequent LC-MS/MS analysis. It has a wide linearity range (1-1000 μg/L, R 2 ≥ 0.995), low method detection limits (0.002-0.036 μg/L), and good recoveries (70.6-107.0 %) at 0.01-10 mg/L of xanthates. Applications of this method showed ubiquitous occurrence of the metal-xanthate complexes as the primary species in flotation wastewaters, which the concentrations were 4.6-28.9-fold higher than those previously determined. It is the first quantitative method established for the analysis of metal-xanthate complexes in water samples, which is of great importance to comprehensively understand the fate and risks of xanthates in the environment., 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 diffusion of iodine species and lead leakage during device degradation represent the main obstacles restricting the commercial application of perovskite solar cells (PSCs). Cobalt loaded ultrathin carbon nanosheets (Co(III)-CNS) derived from biomass are prepared as ion buffer material to construct robust hole transport layers (HTLs). The carbon nanosheets containing trivalent cobalt ions can facilitate the oxidation of the hole transport material while preserving the structural integrity and electrical properties of HTLs under thermal stress, thereby ensuring efficient carrier transport. The two-dimensional ultrathin graphitized lamellar structure of Co(III)-CNS is conducive to alleviate the corrosive effects of the outward diffusion of iodine species on HTLs and silver electrodes, while avoiding irreversible degradation of PSCs. With the improvement of HTL composition and the related interfaces, Co(III)-CNS doped devices can maintain intact device structure under thermal stress and remain above 80% of the original power conversion efficiency (PCE) after thermal aging at 85 oC for 720 h. Notably, the chemical interactions between heteroatoms of self-doped carbon nanosheets and the mobile lead ions can effectively alleviate lead leakage and avoid the potential impacts of device degradation on ecosystem. Ultimately, the Co(III)-CNS doped PSCs with enhanced thermal stability exhibit a champion PCE of 22.32%., (© 2024 Wiley‐VCH GmbH.)

Background: microRNAs (miRNAs) were recognized as a promising source of diagnostic biomarker. Herein, we aim to evaluate the performance of an ultrasensitive method for detecting serum miRNAs using single molecule arrays (Simoa)., Methods: In this study, candidate miRNAs were trained and tested by RT-qPCR in a cohort of PTB patients. Besides that, ultrasensitive serum miRNA detection were developed using the Single Molecule Array (Simoa) platform. In this ultra-sensitive sandwich assay, two target-specific LNA-modified oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA respectively. We characterized its analytical performance and measured miRNAs in the serum of patients with pulmonary tuberculosis and healthy individuals., Results: We identified a five signature including three upregulated (miR-101, miR-196b, miR-29a) and two downregulated (miR-320b, miR-99b) miRNAs for distinguishing PTB patients from HCs, and validated in our 104 PTB patients. On the basis of Simoa technology, we developed a novel, fully automated digital analyser, which can be used to directly detect miRNAs in serum samples without pre-amplification. We successfully detected miRNAs at femtomolar concentrations (with limits of detection [LODs] ranging from 0.449 to 1.889 fM). Simoa-determined serum miR-29a and miR-99b concentrations in patients with PTB ((median 6.06 fM [range 0.00-75.22]), (median 2.53 fM [range 0.00-24.95]), respectively) were significantly higher than those in HCs ((median 2.42 fM [range 0.00-28.64]) ( P < 0.05 ), (median 0.54 fM [range 0.00-9.12] ( P < 0.0001 ), respectively). Serum levels of miR-320b were significantly reduced in patients with PTB (median 2.11 fM [range 0.00-39.30]) compared with those in the HCs (median 4.76 fM [range 0.00-25.10]) ( P < 0.001). A combination of three miRNAs (miR-29a, miR-99b, and miR-320b) exhibited a good capacity to distinguish PTB from HCs, with an area under the curve (AUC) of 0.818 (sensitivity: 83.9%; specificity: 79.7%)., Conclusions: This study benchmarks the role of Simoa as a promising tool for monitoring miRNAs in serum and offers considerable potential as a non-invasive platform for the early diagnosis of PTB., 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 Wu, Tan, Jia, Wu, Liang, Wen, Wang, Zhang, Zhao, Chen, Luo, Liu and Chen.)

Precise DNA replication is fundamental for genetic inheritance. In eukaryotes, replication initiates at multiple origins that are first "licensed" and subsequently "fired" to activate DNA synthesis. Despite the success in identifying origins with specific DNA motifs in Saccharomyces cerevisiae, no consensus sequence or sequences with a predictive value of replication origins have been recognized in metazoan genomes. Rather, epigenetic rules and chromatin structures are believed to play important roles in governing the selection and activation of replication origins. We propose that replication initiation is facilitated by a group of sequence-specific "replication pioneer factors," which function to increase chromatin accessibility and foster a chromatin environment that is conducive to the loading of the prereplication complex. Dysregulation of the function of these factors may lead to gene duplication, genomic instability, and ultimately the occurrence of pathological conditions such as cancer., (© 2024 Wiley Periodicals LLC.)

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 μg/ml) and 7a (38.15 μg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani . The inhibitory activity of compound 7d (10.53 μg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 μg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k , 7a , and 7d showed good selectivity and less toxicity to normal mammalian cells.

Background: Chinese medaka (Oryzias sinensis) is widely distributed in freshwater rivers in China. Similar to the medaka (Oryzias latipes), Chinese medaka has the characteristics of small size, rapid reproductive cycle, and strong adaptability, which makes it suitable as a model organism for studies in basic biology and environmental toxicology. Chinese medaka exhibits distinct sexual dimorphism. However, due to the lack of complete genomic information, the regulation of sex determination and differentiation-related genes in Chinese medaka remains unclear., Methods: Chinese medaka dmrt1 (Osdmrt1) was cloned by PCR, and transgenic individuals of medaka [Tg(CMV:Osdmrt1)] overexpressing Osdmrt1 were generated to investigate the role of Osdmrt1 in sex determination. Western blot was used to validate the integration of the Osdmrt1 into the medaka genome. Tissue sectioning and HE staining were used to identify Tg(CMV:Osdmrt1) physiological gender and phenotype. qRT-PCR was used to analyze the expression of gonad-specific genes., Results: Osdmrt1 was cloned and identified, and it shared similar evolutionary relationships with medaka dmrt1. Tg(CMV:Osdmrt1) exhibited partial sex reversal from female to male in the F2 generation, with genetically female individuals developing testes and producing functional sperm. Additionally, the secondary sexual characteristics of the transgenic females also changed to males., Conclusion: The Chinese medaka dmrt1 gene could convert females to males in medaka., General Significance: These results not only elucidate the function of Chinese medaka dmrt1, but also accumulate knowledge for studying the function of economically important fish genes in model fish by transgenic technology., Competing Interests: Declaration of competing interest, (Copyright © 2023. Published by Elsevier B.V.)

This study presented a dual-layer freshness indicator film produced through electrospinning, combining cellulose acetate and polyvinylidene fluoride with zeolitic imidazolate framework-8 (ZIF-8) loaded with curcumin as the indicator. Our findings demonstrated that ZIF-8 effectively preserved its metal-organic framework structure during curcumin loading, ensuring the inherent color-changing ability of curcumin. The resulting colorimetric film exhibited altered tensile properties and increased water vapor permeability. Improved light stability and storage performance were observed. Compared to single-layer films, the dual-layer structure improved the hydrophilicity and stability of the indicator film. Importantly, the introduced indicator label efficiently captured the dynamic changes of TVB-N during freshness monitoring, providing comprehensive visual information for assessing fish freshness. The synergistic properties of ZIF-8, curcumin, and the dual-layer film structure contributed to an advanced freshness indicator system, providing a multifunctional and effective approach for real-time freshness assessment of fish freshness., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Ltd.)

Probiotics can improve animal growth performance and intestinal health. However, understanding the effects of paraprobiotics on the growth performance and gut microbiota of piglets and how the paraprobiotics exert their impact are still limited. The present study was conducted to investigate the effects of heat-killed Lactobacillus acidophilus IFFI 6005 supplementation on the growth performance, intestinal microbiota, and fecal metabolites of piglets. First, a feed-additive sample of heat-killed Lactobacillus acidophilus IFFI 6005 was prepared by culture. Second, 96 (initial BW = 14.38 ± 0.67 kg, weaning age of 40 days) healthy piglets were selected and randomized into four treatment groups. Each treatment group consisted of three replicates ( n = 8). Pigs were fed a basal diet (NC), basal diet plus antibiotics (PC), basal diet plus Lactobacillus acidophilus IFFI 6005 at 600 g/t (LA, 1.0 × 10 10 cfu/g), and basal diet plus heat-killed Lactobacillus acidophilus IFFI 6005 at 600 g/t (HKLA), respectively; the trial lasted for 30 days. The results showed that the ratios of feed to gain (F:G) and diarrhea rate of both the HKLA and PC groups were significantly lower compared with the NC and LA groups ( p < 0.05); however, there was no significant difference between the HKLA and PC group ( p > 0.05). In addition, the average daily weight gain (ADG) of the HKLA group was significantly higher ( p < 0.05) than that of the other three groups in terms of growth performance. Finally, 16S rRNA sequencing and metabolome analysis based on fecal samples further elaborated that the addition of heat-killed Lactobacillus acidophilus IFFI 6005 to the feed improved the intestinal microbial diversity and abundance ( p < 0.05) and reduced the abundance of pathogenic bacteria ( p < 0.05), but it did not affect the abundance of Lactobacillus ( p > 0.05). Through the comparison of microbial abundance and metabolite content between the two groups (NC&#95;vs&#95;HKLA), the largest differences were found in six microorganisms and 10 metabolites in the intestine ( p < 0.05). These differential metabolites were involved in the digestion, absorption and utilization of protein and starch, as well as in oxidative stress. In summary, addition of heat-killed Lactobacillus acidophilus IFFI 6005 as a new feed additive in piglets has beneficial effects on the growth performance, intestinal bacteria and metabolites, and can be used as an alternative to antibiotics.

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance., 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 Guo, Yang, Mai, Liang, Luo, Zhou, Yu, Wang and Li.)

The bacterial community dynamics and metabolomic profiles in raw yak (Y) milk and cattle-yak (CY) milk during refrigeration at 4 °C were investigated, followed by the elucidation of interspecific differences in milk storage. Bacterial communities and succession patterns were significantly different between the two milk types during refrigeration, with Lactococcus and Pseudomonas being the key distinguishing genera. Moreover, higher network complexity and tighter interactions were observed for the microbial community in CY milk than in Y milk. Furthermore, 7 proteases and 1 lipase potentially contributed to milk spoilage. The metabolomic profiles significantly differed between the milk types during refrigeration. Extended storage time decreased the relative abundances of organic nitrogen compounds and lipids and lipid-like molecules, with a concomitant increase in organic acids and derivatives, particularly in Y milk. Moreover, 9 metabolites, whose levels gradually increased with storage time, were strongly correlated with psychrophiles and thus considered potential markers of deterioration in plateau-characteristic milk. These findings offer a theoretical foundation for augmenting the quality and safety of plateau-characteristic milk and its derivatives, while also helping us understand the microbial and metabolic dynamics in raw milk under extreme environments., 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.)

Mixed culture of microorganisms is an effective method to remove high concentration of phenol in wastewater. At present, it is still a challenge for microorganisms to remove high-concentration phenol from wastewater. In this study, a phenol-degrading consortium was isolated, which could rapidly degrade 1800 mg/L phenol within 30 h, and the highest phenol degradation concentration was 2000 mg/L. Further exploration of how microbial consortium cooperates to promote phenol biodegradation was studied: the core bacteria of the microbial consortium was relatively stable during phenol degradation; the bacteria could improve the adaptability to environment and metabolic ability of phenol, by producing more surfactants and betaine, thereby improving the degradation rate. The determination coefficient (R 2 ) in the machine learning model showed that the back propagation artificial neural network (BP-ANN) can predict the biodegradation of phenol under different conditions, saving time and economic costs. This study explains how microbial consortium cooperates to degrade phenol from the aspects of microbial consortium composition and metabolic analysis, which provides a theoretical basis for mixed culture microorganisms to degrade pollutants., 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: Aerobic glycolysis and the cell cycle are well-established tumor hallmarks. Understanding their relationship could help to unravel the pathogenic mechanisms of breast cancer (BC) and suggest potential new strategies for treatment., Methods: Glycolysis-related genes (GRGs) were downloaded from the Reactome database and screened using univariate Cox analysis. The consensus clustering method was employed to identify a glycolytic activity signature (GAS) using the Gene Expression Omnibus (GEO) dataset. A nomogram risk prediction model was constructed using coefficients from univariate Cox analysis. Immune cell infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Gene co-expression modules were created using weighted correlation network analysis (WGCNA) to identify hub genes. Gene expression in three BC cell lines was quantified using Quantitative Reverse Transcriptase Polymera (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) data was used to examine the relationship between GAS and hub genes. The sensitivity of different groups to cell cycle-related clinical drugs was also examined., Results: BC with high GAS (HGAS) showed high tumor grade and recurrence rate. HGAS was a prognostic indicator of worse overall survival (OS) in BC patients. HGAS BC showed more abundant immune cells and significantly higher expression of immunomodulators compared to BC with low GAS (LGAS). HGAS BC also showed enhanced cell cycle pathway, with high mRNA and protein expression levels of Cyclin B2 (CCNB2), a key component of the cell cycle pathway. Importantly, scRNA-seq analysis revealed that elevated CCNB2 expression was positively correlated with HGAS in triple-negative BC (TNBC). This was validated in clinical samples from TNBC patients. High expression of CCNB2 was found in three BC cell lines, and was also an indicator of poor prognosis. HGAS BC showed high sensitivity to several cell cycle-related clinical drugs, with 9 of these also showing activity in BC with high CCNB2 expression., Conclusions: HGAS was associated with enhanced cell cycle pathway and immune activity in BC. These results suggest that CCNB2 is a potential key therapeutic target in BC patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

The meat production traits of pigs are influenced by the expression regulation of multiple gene types, including mRNAs, miRNAs, and lncRNAs. To study the differences in meat production traits at the transcriptional level among individuals with different growth rates, the longissimus dorsi samples from eight Duroc × Bama Xiang F2 crossbred pigs with a fast growth rate (high gTroup) or a slow growth rate (low group) were selected to perform whole transcriptome sequencing and ceRNA regulatory network construction. This study first analyzed the differences in physiological and biochemical indicators, muscle histological characteristics, and muscle fiber types. A total of 248 mRNAs, 25 miRNAs, and 432 lncRNAs were identified as differentially expressed by whole transcriptome sequencing. Key genes that may influence meat production traits include MTMR14 , PPP1R3A , PYGM , PGAM2 , MYH1 , and MYH7 . The ceRNA regulatory network map showed that ENSSSCG00000042061-ssc-mir-208b- MYH7 , ENSSSCG00000042223-ssc-mir-146a- MTMR14 , ENSSSCG00000045539-ssc-mir-9-3- MYH1 , and ENSSSCG00000047852-ssc-mir-103-1- PPP1R3A may be the key factors affecting meat production traits through their regulatory relationships. This study provides valuable insights into the molecular mechanisms underlying porcine muscle development and can aid in improving meat production traits.

The further development of aqueous zinc (Zn)-ion batteries (AZIBs) is constrained by the high freezing points and the instability on Zn anodes. Current improvement strategies mainly focus on regulating hydrogen bond (HB) donors (H) of solvent water to disrupt HBs, while neglecting the environment of HB-acceptors (O). Herein, we propose a mechanism of chaotropic cation-regulated HB-acceptor via a "super hydrous solvated" structure. Chaotropic Ca 2+ can form a solvated structure via competitively binding O atoms in H 2 O, effectively breaking the HBs among H 2 O molecules, thereby reducing the glass transition temperature of hybrid 1 mol L -1 (M) ZnCl 2 +4 M CaCl 2 electrolyte (-113.2 °C). Meanwhile, the high hydratability of Ca 2+ contributes to the water-poor solvated structure of Zn 2+ , suppressing side reactions and uneven Zn deposition. Benefiting from the anti-freezing electrolyte and high reversible Zn anode, the Zn||Pyrene-4,5,9,10-tetraone (PTO) batteries deliver an ultrahigh capacity of 183.9 mAh g -1 at 1.0 A g -1 over 1600-time stable cycling at -60 °C. This work presents a cheap and efficient aqueous electrolyte to simultaneously improve low-temperature performances and Zn stability, broadening the design concepts for antifreeze electrolytes., (© 2024 Wiley-VCH GmbH.)

After peripheral nerve injury (PNI), the long-term healing process at the injury site involves a progressive accumulation of collagen fibers and the development of localized scar tissue. Excessive formation of scar tissue within nerves hinders the process of nerve repair. In this study, we demonstrate that scar formation following nerve injury induces alterations in the local physical microenvironment, specifically an increase in nerve stiffness. Recent research has indicated heightened expression of Piezo1 in Schwann cells (SCs). Our findings also indicate Piezo1 expression in SCs and its association with suppressed proliferation and migration. Transcriptomic data suggests that activation of Piezo1 results in elevated expression of senescence-associated genes. GO enrichment analysis reveals upregulation of the TGF-β pathway. Overall, our study highlights the potential for Piezo1-induced signaling to regulate SC senescence and its potential significance in the pathophysiology of fibrotic scar formation surrounding peripheral nerves., 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 B.V. All rights reserved.)

This study aimed to evaluate the effects of Clostridium butyricum ( C. butyricum ) on the prevention of the diarrhea rates and growth performances of weaned piglets induced by Escherichia coli K88 ( E. coli K88). Twenty-four weaned piglets (6.92 ± 0.11 kg) were randomly assigned to one of three treatment groups for a period of 21 days. Each group consisted of eight pigs, with each pig being housed in an individual pen. Group I received the control diet along with normal saline, Group II received the control diet along with E. coli K88, and Group III received the control diet supplemented with 5 × 10 8 CFU/kg of C. butyricum and E. coli K88. We examined alterations in rectal microbiota and metabolites, analyzed the incidence of diarrhea, and investigated the interactions between microbiota and metabolites through the application of Illumina MiSeq sequencing and liquid chromatography-mass spectrometry. The results showed that, from days 14 to 21, the diarrhea incidence in Group III decreased significantly by 83.29% compared to Group II ( p < 0.05). Over the entire experimental duration, the average daily feed intake of Group III decreased significantly by 11.13% compared to Group I ( p < 0.05), while the diarrhea incidence in Group III decreased by 71.46% compared to Group II ( p < 0.05). The predominant microbial flora in the rectum consisted of Firmicutes (57.32%), Bacteroidetes (41.03%), and Proteobacteria (0.66%). Administering E. coli K88 orally can elevate the relative abundance of Megasphaera ( p < 0.05). Conversely, the supplementation of C. butyricum in the diet reduced the relative abundance of Megasphaera ( p < 0.05), while increasing the relative abundance of unclassified&#95;f&#95; Lachnospiraceae ( p < 0.05). Rectal metabolomics analysis revealed that supplementing C. butyricum in the feed significantly altered the amino acids and fatty acids of the piglets infected with E. coli K88 ( p < 0.05). The correlation analysis showed that the occurrence of diarrhea was inversely related to adipic acid ( p < 0.05) and positively associated with (5-hydroxyindol-3-YL) acetic acid and L-aspartic acid ( p < 0.05). Prevotella &#95;1 exhibited a negative correlation with octadecanoic acid ( p < 0.05). Prevotellaceae &#95;UCG-005 showed a negative correlation with (5-hydroxyindol-3-YL) acetic acid ( p < 0.05). The findings from this research study aid in probiotic development and the enhancement of healthy growth in weaned piglets.

Selenium is among the important trace elements that influence the quality of meat. Although it has been established that the gut microbiota is closely associated with selenium metabolism, it has yet to be determined whether these microbes influence the accumulation of selenium in muscles. To identify gut microbiota that potentially influence the deposition of selenium in muscles, we compared the colonic microbial composition of pigs characterized by high and low contents of selenium in the longissimus dorsi muscle and accordingly detected a higher abundance of the bacterium Prevotella copri (P. copri) in pigs with a higher muscle selenium content. To verify the effect of P. copri, 16 pigs weighing approximately 61 kg were fed either a basal diet or a basal diet supplemented with P. copri (1.0 × 10 10  CFU/kg feed) for 45 days. The results revealed significant increases in the contents of selenium and selenoprotein in the serum and longissimus dorsi muscle of fattening pigs fed the P. copri-supplemented diet. Moreover, supplementing the feed of pigs with P. copri was observed to promote significant improvement in the antioxidant capacity and quality of meat, including drip loss, pH, and meat color. In conclusion, our findings in this study indicate that P. copri has potential utility as a dietary supplement for improving the selenium status and meat quality in fattening pigs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To observe the effect of Wenyang Baidu Yin on early microcirculation indicators in patients with sepsis (syndrome of Yang deficiency and turbid toxin), analyze the specific therapeutic effect, and provide a new perspective for clinical treatment of microcirculation disorders in sepsis., Methods: Sixty-four patients with sepsis admitted to the intensive care unit (ICU) of Shanxi Province Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to July 2023 were enrolled. Patients were divided into control group and observation group by randomly number table method, with 32 cases in each group. The control group received conventional Western medicine treatment. On the basis of conventional Western medicine treatment, the observation group was given Wenyang Baidu Yin 200 mL/d (100 mL each time, with an interval of 12 hours) orally or by nasal feeding for 3 consecutive days. The central venous oxygen saturation (ScvO 2 ), difference of central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO 2 ), arterial lactic acid (Lac), pulse perfusion index (PI), capillary refill time (CRT), and skin mottling score (SMS) of two groups were detected before treatment and at 6, 12, 24, and 48 hours of treatment; simultaneously record the traditional Chinese medicine (TCM) syndrome score before treatment and at 72 hours of treatment, as well as the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) before treatment and at 24 hours and 72 hours of treatment., Results: There were no statistically significant differences in gender, age, and various microcirculation indicators before treatment between the two groups, indicating consistent baseline characteristics. Compared with before treatment, the microcirculation indicators ScvO 2 , Pcv-aCO 2 , Lac, PI, CRT, and SMS in both groups showed significant improvement after treatment. Moreover, the observation group showed more significant improvements in Lac and PI compared to the control group at 24 hours and 48 hours of treatment [Lac (mmol/L): 2.45±0.92 vs. 3.07±1.07 at 24 hours, 2.06±0.87 vs. 2.59±1.01 at 48 hours; PI: 3.45±0.89 vs. 2.92±0.98 at 24 hours, 3.56±0.99 vs. 3.01±0.87 at 48 hours, all P < 0.05]. CRT and SMS showed more significant improvements compared to the control group at 48 hours of treatment [CRT (s): 2.04±1.08 vs. 2.62±0.99, SMS: 0.5 (0.0, 1.0) vs. 1.0 (1.0, 1.0), both P < 0.05], while there were no statistically significant differences in ScvO 2 and Pcv-aCO 2 at each time point between the two groups. After treatment, the APACHE score, SOFA score, and TCM syndrome score improved in both groups compared to before treatment, and the improvement degree of each score in the observation group was significantly higher than that in the control group [72 hours APACHE II score: 15.0 (12.2, 16.0) vs. 17.0 (13.5, 20.0), 72 hours SOFA score: 6.0 (6.0, 8.0) vs. 10.0 (8.0, 13.0), 72 hours TCM syndrome score: 10.13±3.73 vs. 14.63±5.55, all P < 0.05]., Conclusions: On the basis of conventional Western medicine treatment, the combination of Wenyang Baidu Yin can significantly improve microcirculation disorders in patients with sepsis (syndrome of Yang deficiency and turbid toxin) to a certain extent, thereby improving patient prognosis.

Abstract: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Background: The expression of CYP19A1 has implications for the prognosis of female bladder cancer. However, this study aimed to explore the association between single nucleotide polymorphisms (SNPs) in CYP19A1 and bladder cancer risk, as no prior research has addressed this association., Research Design and Methods: We selected and genotyped five CYP19A1 SNPs (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) in 217 patients and 550 controls using the Agena MassARRAY system. Logistic regression analysis was employed to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Bioinformatics predicted SNP functions and CYP19A1 involving pathways., Results: Our study revealed a significant association between bladder cancer risk and four SNPs (rs4646 (AC vs. CC: OR = 1.71, FDR- p  = 0.005), rs6493487 (G vs. A: OR = 0.68, FDR- p  = 0.011), rs1062033 (G vs. C: OR = 0.36, FDR- p  < 0.001), and rs17601876 (GA vs. GG: OR = 1.66, FDR- p  = 0.008)) in CYP19A1 . The three SNPs (rs4646, rs1062033, and rs17601876) were significantly correlated with CYP19A1 expression levels in normal whole blood ( p  < 0.05). Moreover, CYP19A1 was found to primarily participate in the steroid hormone biosynthesis and metabolic pathways., Conclusions: Consequently, CYP19A1 gene polymorphisms may play a crucial role in the genetic susceptibility to bladder cancer.

Coronatine, an analog of Jasmonic acid (JA), has been shown to enhance crop tolerance to abiotic stresses, including chilling stress. However, the underlying molecular mechanism remains largely unknown. In this study, we investigated the effect of Coronatine on cotton seedlings under low temperature using transcriptomic and metabolomics analysis. Twelve cDNA libraries from cotton seedlings were constructed, and pairwise comparisons revealed a total of 48,322 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the involvement of these unigenes in various metabolic pathways, including Starch and sucrose metabolism, Sesquiterpenoid and triterpenoid biosynthesis, Phenylpropanoid biosynthesis, alpha-Linolenic acid metabolism, ABC transporters, and Plant hormone signal transduction. Additionally, substantial accumulations of jasmonates (JAs), abscisic acid and major cell wall metabolites were observed. Transcriptome analysis revealed differential expression of regulatory genes, and qRT-PCR analysis confirmed the expression patterns of 9 selected genes. Co-expression analysis showed that the JA-responsive genes might form a network module with ABA biosynthesis genes or cell wall biosynthesis genes, suggesting the existence of a COR-JA-cellulose and COR-JA-ABA-cellulose regulatory pathway in cotton seedlings. Collectively, our findings uncover new insights into the molecular basis of coronatine--associated cold tolerance in cotton seedlings., 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., (Published by Elsevier Masson SAS.)

Background: The coronary artery calcium score (CACS) has been shown to be an independent predictor of cardiovascular events. The traditional coronary artery calcium scoring algorithm has been optimized for electrocardiogram (ECG)-gated images, which are acquired with specific settings and timing. Therefore, if the artificial intelligence-based coronary artery calcium score (AI-CACS) could be calculated from a chest low-dose computed tomography (LDCT) examination, it could be valuable in assessing the risk of coronary artery disease (CAD) in advance, and it could potentially reduce the occurrence of cardiovascular events in patients. This study aimed to assess the performance of an AI-CACS algorithm in non-gated chest scans with three different slice thicknesses (1, 3, and 5 mm)., Methods: A total of 135 patients who underwent both LDCT of the chest and ECG-gated non-contrast enhanced cardiac CT were prospectively included in this study. The Agatston scores were automatically derived from chest CT images reconstructed at slice thicknesses of 1, 3, and 5 mm using the AI-CACS software. These scores were then compared to those obtained from the ECG-gated cardiac CT data using a conventional semi-automatic method that served as the reference. The correlations between the AI-CACS and electrocardiogram-gated coronary artery calcium score (ECG-CACS) were analyzed, and Bland-Altman plots were used to assess agreement. Risk stratification was based on the calculated CACS, and the concordance rate was determined., Results: A total of 112 patients were included in the final analysis. The correlations between the AI-CACS at three different thicknesses (1, 3, and 5 mm) and the ECG-CACS were 0.973, 0.941, and 0.834 (all P<0.01), respectively. The Bland-Altman plots showed mean differences in the AI-CACS for the three thicknesses of -6.5, 15.4, and 53.1, respectively. The risk category agreement for the three AI-CACS groups was 0.868, 0.772, and 0.412 (all P<0.01), respectively. While the concordance rates were 91%, 84.8%, and 62.5%, respectively., Conclusions: The AI-based algorithm successfully calculated the CACS from LDCT scans of the chest, demonstrating its utility in risk categorization. Furthermore, the CACS derived from images with a slice thickness of 1 mm was more accurate than those obtained from images with slice thicknesses of 3 and 5 mm., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-247/coif). X.C. is an employee of Philips Healthcare. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

NLRP6 plays a crucial role in maintaining intestinal homeostasis by regulating the interaction between the intestinal mucosa and the microbiota. However, the impact of NLRP6 deficiency on intestinal damage following hematopoietic stem cell transplantation (HSCT) remains poorly understood. In this study, we established a syngeneic HSCT mouse model using C57BL/6 mice as donors and NLRP6-/- or C57BL/6 mice as recipients. Our findings revealed that NLRP6 deficiency had minimal influence on peripheral blood cell counts and splenic immune cell proportions in transplanted mice. However, it exacerbated pathological changes in the small intestine on day 14 post-transplantation, accompanied by increased proportions of macrophages, dendritic cells, and neutrophils. Furthermore, the NLRP6 deficiency resulted in elevated expression of MPO and CD11b, while reducing the levels mature caspase-1 and mature IL-1β in the intestine. Moreover, the NLRP6 deficiency disturbed the expression of apoptosis-related molecules and decreased the tight junction protein occludin. Notably, recipient mice with NLRP6 deficiency exhibited lower mRNA expression levels of antimicrobial genes, such as Reg3γ and Pla2g2a. The short-term increase in inflammatory cell infiltration caused by NLRP6 deficiency was associated with intestinal damage, increased apoptosis, reduced expression of antimicrobial peptides, and impaired intestinal repair. Taken together, our findings demonstrate that the loss of NLRP6 exacerbates post-transplantation intestinal damage in recipient mice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We investigated the optimal number of valid measurements (VMs) for the attenuation coefficient (AC) to assess liver steatosis using attenuation imaging (ATI) and explored factors that may affect AC measurement in patients with metabolic dysfunction-associated fatty liver disease (MAFLD)., Materials and Methods: A total of 139 patients with MAFLD who underwent ATI and liver biopsy were enrolled. Hepatic steatosis was graded as S0-3 according to the SAF scoring system. The AC values from 1, 2, 3, 5, and 7 VMs were compared with the degree of liver steatosis. The correlation between AC values from different VMs was analyzed. The diagnostic performance of AC from different VMs at each steatosis grade was compared. The factors related to AC were identified using linear regression analysis., Results: The mean AC values from 1, 2, 3, 5, and 7 VMs were not significantly different between grades S0-3 (p=n.s. for all). Bland-Altman analysis showed the mean difference in AC values of 3 VMs and 7 VMs was 0.003 dB/cm/MHz, which was smaller compared with 2 VMs, and close to 5 VMs. The intraclass correlation coefficients of AC were all > 0.90 among different VM groups. AC values from different VMs all significantly predicted steatosis grade ≥S1, ≥S2, and S3 without significant statistical differences (p=n.s. for all). The multivariate analysis showed that the hepatic steatosis grade and triglyceride level were factors independently associated with AC., Conclusion: Three valid measurements of AC may be adequate to ensure the accuracy and reproducibility of hepatic steatosis assessment. The degree of liver steatosis and the triglyceride level significantly affected AC values., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

In this study, a novel Z-scheme heterojunction on bismuth vanadium/cadmium sulfide (BiVO 4 /0.6CdS) was developed and evaluated for simultaneous photocatalytic removal of combined tetracycline (TC) and hexavalent chromium Cr(Ⅵ) pollution under visible light. Based on the analysis of intermediate products and theoretical calculation, the property of the intermediate products of TC degradation and the effect of built-in electric field (IEF) of composite materials on photo-generated carrier separation were illustrated. According to the experiments and evaluation results, the performance of BiVO 4 /0.6CdS is higher than CdS 2.83 times and 4.82 times under the visible light conditions, with the aspect of simultaneous oxidizing TC and reducing Cr(Ⅵ), respectively. The catalyst has a faster removal rate in the binary composite pollution system than the single one. Therefore, the photocatalytic degradation of TC using BiVO 4 /0.6CdS can reduce the toxic effect of TC on the environment. The aforementioned evaluation provides a new design strategy for Z-scheme heterojunction to simultaneous photocatalytic degradation of composite organic and inorganic pollutants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kai Huang reports financial support was provided by National Natural Science Foundation of China. Kai Huang reports a relationship with Guangdong & Guangxi Cooperation Special Key Fund Project that includes: funding grants. 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 Inc. All rights reserved.)

With the rapid development of intensive animal husbandry in the livestock industry, large quantities of manure waste containing phytate phosphorus are being generated. Phytase can effectively solve the problem of high phosphorus pollution in the feces of monogastric animals. Enviropig, which produces phytase in the salivary glands and secretes the enzyme in the saliva, were first generated in 1999. However, phytase is easily inactivated during digestion. To address this problem, cleavage-resistant phytase transgenic pigs were generated using handmade cloning in this study. Transgene construction was improved and three cell lines carrying Cafp were obtained. In total, 810 blastocysts were generated and 712 good-quality were transferred into six recipients. Fourteen piglets were born, of which six survived after weaning. Polymerase chain reaction and sequencing results showed that seven (three live and four dead) of the fourteen piglets carried Cafp. Phytase activity in the saliva of the six live cloned pigs was tested at four months of age, and only one pig had 0.155 FTU/mL enzyme activity. The other five pigs may not have been activated in the transgenic parotid gland. Among all the transgenic pigs, the highest phosphorus digestion rate was 59.2% of intake, representing a 25.4% decrease in fecal emission compared to the average of controls. Immunohistochemical results on the three Cafp-positive pigs that died after six months of age showed that the transgene was only expressed in parotid glands, confirming tissue-specific gene expression. In conclusion, cleavage-resistant phytase transgenic pigs were successfully produced through handmade cloning. The cloned pigs offer a unique biological approach to managing phosphorus nutrition and environmental pollution in animal husbandry., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4 mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1β, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500 ng/mL) / adenosine triphosphate (5 mM) and treated it with GB (10, 20, and 40 μM). GB upregulated the expression of mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of reactive oxygen species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1β, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5 mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy., 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 Masson SAS.. All rights reserved.)

Sepsis-related brain injury (SRBI) refers to brain dysfunction and structural damage caused by sepsis, which is characterized by inflammation, oxidative stress, and destruction of the blood-brain barrier. Pioglitazone is a PPAR-γ agonist in which PPAR-γ acts as an inflammatory modulator, determining the relationship between PPAR-γ and SRBI and inflammatory state is critical for the disease. This study aimed to construct a drug-target-disease network for SRBI and Pioglitazone based on network pharmacology, and to investigate the therapeutic effect and potential mechanism of Pioglitazone in SRBI induced by lipopolysaccharide (LPS) in rats through transcriptomics. To establish a rat Model of SRBI by intraperitoneal injection of LPS (10 mg/kg): SD rats were divided into Control, Model (LPS), Pioglitazone, (LPS + Pioglitazone) and GW9662 group (LPS+GW9662). The effects and potential mechanisms of Pioglitazone in the treatment of SRBI were studied using biochemical indexes, pathological changes and transcriptome-sequencing (RNA-seq). RNA-seq results showed 620 DEGs between the Model and the Pioglitazone groups. Enrichment analysis involved multiple inflammatory response processes and chemokine receptor binding functions. TLR4 and CXCL10 in the Toll signaling pathway may play an important role in SRBI as important targets. Pioglitazone may ameliorate SRBI through the PPAR-γ/TLR4/CXCL10 pathway., 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 B.V. All rights reserved.)

Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients., Competing Interests: Declaration of competing interest This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee. It was approved by the Institutional Review Board of Beijing Huilongguan Hospital. Informed, written consent was obtained from all subjects involved in the study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Up to 80 % of chemotherapeutic drugs induce myelosuppression in patients. Chemotherapy not only impairs of hematopoietic stem cells (HSCs) but also damages bone marrow niches (vascular and endosteal). Current treatments for myelosuppression overlook these chemotherapy-induced damages to bone marrow niches and the critical role of niche restoration on hematopoietic regeneration. Ginsenoside protopanaxatriol (PPT) protects vascular endothelium from injury, while icariin (ICA) promotes osteogenic differentiation. The combination of PPT and ICA aims to restore damaged vascular and endosteal niches, thus rejuvenating HSCs for treating myelosuppression., Purpose: This study aims to develop effective, bone marrow niche-directed PPT/ICA therapies for treating chemotherapy-induced myelosuppression., Methods: 3D cell spheroids were used to investigate the effects of PPT/ICA on cell-cell interactions in vascular niches, osteogenesis, and extracellular matrix (ECM) secretion in endosteal niches. In vitro mimic niche models were designed to access the drug combination's efficacy in rejuvenating and mobilizing in HSCs within bone marrow niches. The delivery capability of PPT/ICA to key niche cell types (mesenchymal stromal cells (MSCs), endothelial cells (ECs), and osteoblasts (OBs)) via nanocarriers has been determined. DSS6 peptide-modified nanoparticles (DSS6-NPs) were prepared for specific co-delivery of PPT/ICA into key niche cell populations in vivo., Results: PPT can prevent vascular niche injury by restoring vascular EC cell-cell adhesion and the intercellular interactions between ECs and MSCs in 5-fluorouracil (5-FU)-damaged cell spheroids. ICA repaired 5-FU-damaged endosteal niches by promoting osteogenesis and ECM secretion. The combination of PPT and ICA restores key HSC niche factor gene expressions, normalizing HSC differentiation and mobilization. The in vitro cellular uptake efficiency of nanocarriers in a mimic niche is positively correlated with their in vivo delivery into bone marrow niche cells. DSS6-NPs greatly enhance the delivery of PPT/ICA into MSCs and OBs within bone marrow niches. Co-loading of PPT/ICA into DSS6-NPs effectively repairs damaged bone marrow niches and promotes HSC rejuvenation in vivo., Conclusion: The combination of PPT and ICA effectively prevents injury to the vascular and endosteal niches, thereby promoting hematopoietic regeneration in the bone marrow. This study provides novel niche-directed PPT/ICA therapies for managing chemotherapy-induced myelosuppression., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The treatment efficiency of acidic phenol-containing wastewater is hindered by the absence of efficient acid-resistant phenol-degrading bacteria, and the acid-resistant mechanism of such bacteria remains poorly studied. In this study, the acid-resistant strain Hly3 was used as a research model to investigate its ability to degrade phenol and its underlying mechanism of acid resistance. Strain Hly3 exhibited robust acid resistance, capable of surviving in extremely acidic environments (pH 3) and degrading 1700 mg L -1 phenol in 72 h. Through the physiological response analysis of strain Hly3 to pH, the results indicated: firstly, the strain could reduce the relative permeability of the cell membrane and increase EPS secretion to prevent H + from entering the cell (shielding effect); secondly, the strain could accumulate more buffering substances to neutralize the intracellular H + (neutralization effect); thirdly, the strain could expel H + from the cell by enhancing H + -ATPase activity (pumping effect); finally, the strain produced more active scavengers to reduce the toxicity of acid stress on cells (antioxidant effect). Subsequently, combining liquid chromatography-mass spectrometry (LC-MS) technology with exogenous addition experiments, it was verified that the acid resistance mechanism of microorganisms is achieved through the activation of acid-resistant response systems by glutamine, thereby enhancing functions such as shielding, neutralization, efflux, and antioxidation. This study elucidated the acid resistance mechanism of Acinetobacter pittii, providing a theoretical basis and guidance for the treatment of acidic phenol-containing wastewater., 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.)

Artificial regulation of plant rhizosphere microbial communities through the synthesis of microbial communities is one of the effective ways to improve plant stress resistance. However, the process of synthesizing stress resistant microbial communities with excellent performance is complex, time-consuming, and costly. To address this issue, we proposed a novel strategy for preparing functional microbial communities. We isolated a cultivable cold tolerant bacterial community (PRCBC) from the rhizosphere of peas, and studied its effectiveness in assisting rice to resist stress. The results indicate that PRCBC can not only improve the ability of rice to resist cold stress, but also promote the increase of rice yield after cold stress relieved. This is partly because PRCBC increases the nitrogen content in the rhizosphere soil, and promotes rice's absorption of nitrogen elements, thereby promoting rice growth and enhancing its ability to resist osmotic stress. More importantly, the application of PRCBC drives the succession of rice rhizosphere microbial communities, and promotes the succession of rice rhizosphere microbial communities towards stress resistance. Surprisingly, PRCBC drives the succession of rice rhizosphere microbial communities towards a composition similar to PRCBC. This provides a feasible novel method for artificially and directionally driving microbial succession. In summary, we not only proposed a novel and efficient strategy for preparing stress resistant microbial communities to promote plant stress resistance, but also unexpectedly discovered a possible directionally driving method for soil microbial community succession., 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.)

Natural sweeteners generally refer to a sweet chemical component directly extracted from nature or obtained through appropriate modifications, mainly secondary metabolites of plants. Compared to the first-generation sweeteners represented by sucrose and the second-generation sweeteners represented by sodium cyclamate, natural sweeteners usually have high sweetness, low-calorie content, good solubility, high stability, and rarely toxic side effects. Historically, researchers mainly focus on the function of natural sweeteners as substitutes for sugars in the food industry. This paper reviews the bioactivities of several typical natural sweeteners, including anti-cancer, anti-inflammatory, antioxidant, anti-bacterial, and anti-hyperglycemic activities. In addition, we have summarized the extraction, physicochemical properties, and application of natural sweeteners. The article aimed to comprehensively collate vital information about natural sweeteners and review the potentiality of tapping bioactive compounds from natural products. Hopefully, this review provides insights into the further development of natural sweeteners as therapeutic agents and functional foods., Competing Interests: Declaration of competing interest The authors declared that the review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We declare that we have no financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Identifying the biomarkers from the personalized gene interaction network of individual patients is important for disease diagnosis. However, existing methods not only ignore the prior biomarkers for practical use but also ignore the observability of the entire system. Therefore, this paper proposes a new constrained multi-objective optimization-based temporal network observability model (CMTNO) to identify biomarkers, which not only requires minimizing the number of selected nodes including ordinary nodes and prior nodes (the first optimization objective) but also maximizing the number of selected prior nodes (the second optimization objective) on the premise of ensuring network observability (the constraint condition). Considering the temporal feature of cancer (patients belong to different stages and each patient contains one task), an experience learning-based constrained multi-objective evolutionary algorithm is designed to solve the CMTNO problems. The selected probabilities of ordinary nodes and prior nodes are treated as experience, stored in two separate archives and updated by the optimal solutions on each task. Experience utilization refers to using two archives to generate new initial populations for new patients, in order to improve the optimization efficiency of the algorithm. Besides, a two-step neighbor-based connectivity method is proposed to distinguish different nodes with similar connectivity to further improve the effectiveness of archives. The proposed model and algorithm are evaluated on three kinds of cancer patients' data under two kinds of network models, and results show their effectiveness in identifying effective biomarkers.