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Wen-Jie Tang,1,* Yun-Shi Liang,2,* Jing Yan,3 Yue Hu,4 Mei-Li Sun,5 Guo-Shun Liu,1 Xiao-Huan Pan,6 Xin-Hua Wei,1 Xin-Qing Jiang,1 Yuan Guo1 1Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of China; 2Department of Pathology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of China; 3Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 4Department of Ultrasound, Sun Yat-Sen Memorial Hospital Sun Yat-Sen University, Guangzhou 510120, People’s Republic of China; 5Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 6Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Guo; Xin-Qing JiangDepartment of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, No. 1 Panfu Road, Guangzhou, Guangdong 510180, People’s Republic of ChinaTel +86 136-3249-8569; +86 181-0281-2838Fax +86-20-81048873Email eyguoyuan@scut.edu.cn; eyjiangxq@scut.edu.cnBackground: Encapsulated papillary carcinoma (EPC) of the breast is a rare entity. EPC can be underappreciated on percutaneous biopsy, which may require additional procedures if invasion is not recognized preoperatively. We aimed to investigate the magnetic resonance imaging (MRI) phenotypes correlated with preoperative pathological risk stratification for clinical guidance.Materials and Methods: The preoperative MRI scans of 30 patients diagnosed with 36 EPCs in multiple centers between August 2015 and February 2020 were reviewed by two breast radiologists. According to the WHO classification published in 2019, EPCs were classified into two pathological subtypes: encapsulated papillary carcinoma and encapsulated papillary carcinoma with invasion. Clinicopathological analysis of the two subtypes and MR feature analysis were performed.Results: Evaluation of the MRI phenotypes and pathological subtype information revealed that not circumscribed (P=0.04) was more common in EPCs with invasion than in EPCs. There was a significant difference in the age of patients (P=0.05), and the risk increased with age. The maximum diameter of the tumor increased with tumor risk, but there was no significant difference (P=0.36). Nearly half of the EPC with invasion patients showed hyperintensity on T1WI (P=0.19). A total of 63.6% of the EPC with invasion group showed non-mass enhancement surrounding (P=0.85). In addition, 29 patients (96.7%) had no axillary lymph node metastasis, and only one patient with EPC with invasion had axillary lymph node metastasis. Further pathological information analysis of EPCs showed that higher Ki-67 levels were more common in patients with EPCs with invasion (P=0.04). A total of 29 patients (96.7%) had the luminal phenotype, and one patient with EPC with invasion had the Her-2-positive phenotype.Conclusion: The margin, age and Ki-67 level were the key features for EPC risk stratification. In addition, these MRI signs, including a larger tumor, non-mass enhancement surrounding and axillary lymph node metastasis, may be suggestive of a high-risk stratification. Therefore, MRI phenotypes may provide additional information for the risk stratification of EPCs.Keywords: carcinoma, papillary, breast neoplasms, magnetic resonance imaging, pathology

Spiro[fluorene-9,9′-xanthene] (SFX) bipolar hosts bearing one, two and three quinolyl substituents, namely SFX-bPy, SFX-DbPy and SFX-TbPy, were designed and synthesized for phosphorescent organic light emitting diodes (PhOLEDs). The successive substitution of quinoline at 2′, 2 and 7′ positions of SFX results in reduced LUMO energy levels while leaving the HOMO energy levels nearly intact. The impact of quinoline substitution in these SFX-based hosts on PhOLED performance was investigated in detail through green and red model devices. For the green emitting devices, the device based on SFX-bPy host showed better performance (23.6 cd A-1, 23.4 lm W-1, 6.3%) due to high triplet energy level (T1) and balanced carriers-transporting ability. In contrast, for the red PhOLED devices, the device hosted by SFX-DbPy displayed higher performance (15.8 cd A-1, 16.0 lm W-1, 9.1%), attributable to the well matched T1 and separated frontier molecular orbitals. This work thus sheds light on the rational design of SFX-based bipolar hosts for more efficient PhOLEDs.

Objective: To evaluate the diagnostic accuracy of dual-source CT (DSCT) prospective ECG-triggering coronary angiography in patients with different heart rate (HR).Methods: 103 patients with suspected coronary artery disease underwent DSCT prospective ECG-triggered coronary angiography and invasive coronary angiography (ICA). The patients were grouped by HR during CT scans: low HR (≤60 bpm, n = 34); medium HR (60 < HR ≤ 70 bpm, n = 36) and high HR (>70 bpm, n = 33). The sensitivity and specificity of DSCT in detecting ≥50% stenosis were compared among subgroups where ICA was the gold standard. Image quality was scored using a 4-point scale.Results: A total of 1,580 (95.9%) coronary artery segments were evaluable. Sensitivity and specificity were 82.8% and 98.4%, 88.3% and 98.7%, and 80.3% and 98.6% for different subgroups (all p > 0.05). The overall area under the curve of the receiver-operating characteristic analysis was 0.94. The image quality scores were 3.1 ± 0.3, 3.1 ± 0.3 and 3.0 ± 0.4 for subgroups (p > 0.05). The overall average effective radiation dose was 3.60 ± 1.60 mSv.Conclusion: DSCT coronary angiography with prospective ECG-triggering could be just as accurate in patients with medium to high HR compared to those with low HR. [ABSTRACT FROM AUTHOR]

Corynebacterium glutamicum, a well-studied industrial model microorganism, has garnered widespread attention due to its ability for producing amino acids with a long history. In recent years, research efforts have been increasingly focused on exploring its potential for producing various organic acids beyond amino acids. Organic acids, which are characterized by their acidic functional groups, have diverse applications across industries such as food, agriculture, pharmaceuticals, and biobased materials. Leveraging advancements in metabolic engineering and synthetic biology, the metabolic pathways of C. glutamicum have been broadened to facilitate the production of numerous high-value organic acids. This review summarizes the recent progress in metabolic engineering for the production of both amino acids and other organic acids by C. glutamicum. Notably, these acids include, amino acids (lysine, isoleucine, and phenylalanine), TCA cycle-derived organic acids (succinic acid, α-ketoglutaric acid), aromatic organic acids (protocatechuate, 4-amino-3-hydroxybenzoic acid, anthranilate, and para-coumaric acid), and other organic acids (itaconic acid and cis, cis-muconic acid)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The excessive accumulation of nitrogen pollutants (mainly nitrate, nitrite, ammonia nitrogen, hydrazine, and urea) in water bodies seriously disrupts the natural nitrogen cycle and poses a significant threat to human life and health. Electrolysis is considered a promising method to degrade these nitrogenous pollutants in sewage, with the advantages of high efficiency, wide generality, easy operability, retrievability, and environmental friendliness. For particular energy devices, including metal-nitrate batteries, direct fuel cells, and hybrid water electrolyzers, the realization of energy valorization from sewage purification processes ( e.g. , valuable chemical generation, electricity output, and hydrogen production) becomes feasible. Despite the progress in the research on pollutant electrodegradation, the development of electrocatalysts with high activity, stability, and selectivity for pollutant removal, coupled with corresponding energy devices, remains a challenge. This review comprehensively provides advanced insights into the electrodegradation processes of nitrogenous pollutants and relevant energy valorization strategies, focusing on the reaction mechanisms, activity descriptors, electrocatalyst design, and actuated electrodes and operation parameters of tailored energy conversion devices. A feasibility analysis of electrodegradation on real wastewater samples from the perspective of pollutant concentration, pollutant accumulation, and electrolyte effects is provided. Challenges and prospects for the future development of electrodegradation systems are also discussed in detail to bridge the gap between experimental trials and commercial applications.

Background: A phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed., Objectives: The aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials., Methods: MET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups., Results: H9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting., Conclusions: We confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials., 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.)

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of Botrytis cinerea , which suffers from limited availability of genetic engineering tools. Here, Yarrowia lipolytica was engineered to enable de novo biosynthesis of ABA. To overcome the rate-limiting P450 enzymes, systematic engineering strategies were implemented. Firstly, the dissolved oxygen was increased to boost the activity of P450 enzymes. Secondly, the expansion of endoplasmic reticulum was implemented to improve the functional expression of P450 enzymes. Lastly, rate-limiting enzymes were assembled to facilitate substrate trafficking. Moreover, ABA production was further improved by strengthening the mevalonate pathway. Finally, the engineered strain produced 1221.45 mg/L of ABA in a 5-L bioreactor. The study provides effective approaches for alleviating rate-limiting P450 enzymes to enhance ABA production and achieve competitive industrial-level ABA production in Y. lipolytica ., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Systematic metabolic engineering of Yarrowia lipolytica for efficient production of phytohormone abscisic acid”., (© 2024 The Authors.)

Geranylgeraniol (GGOH) is a crucial component in fragrances and essential oils, and a valuable precursor of vitamin E. It is primarily extracted from the oleoresin of Bixa orellana , but is challenged by long plant growth cycles, severe environmental pollution, and low extraction efficiency. Chemically synthesized GGOH typically comprises a mix of isomers, making the separation process both challenging and costly. Advancements in synthetic biology have enabled the construction of microbial cell factories for GGOH production. In this study, Yarrowia lipolytica was engineered to efficiently synthesize GGOH by expressing heterologous phosphatase genes, enhancing precursor supplies of farnesyl diphosphate, geranylgeranyl pyrophosphate, and acetyl-CoA, and downregulating the squalene synthesis pathway by promoter engineering. Additionally, optimizing fermentation conditions and reducing reactive oxygen species significantly increased the GGOH titer to 3346.47 mg/L in a shake flask. To the best of our knowledge, this is the highest reported GGOH titer in shaking flasks to date, setting a new benchmark for terpenoid production.

Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis, and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal, relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bacteria of the genus Shewanella in the class Gammaproteobacteria are widely distributed in marine environments. Shewanella sp. H8, was isolated from a red algae sample collected from Nelson Island, Antarctica. Here, we present the complete genome sequence of strain H8, which consists of a single circular chromosome comprising 4,490,743 nucleotides with 40.59 % G + C content without any plasmid. In total, 3983 protein coding genes, 95 tRNA genes, and 25 rRNA genes were obtained. Genomic analysis of strain H8 showed that it contains four cold shock proteins and three fatty acid desaturases and possesses the potential to synthesize hglE-KS, arylpolyene, betalactone and RiPP-like compounds. Through genomic annotation, 91 protease-encoding genes were identified within the genome of strain H8. These proteases are classified into six categories based on their catalytic types. Among these proteases, metalloproteinases and serine proteases are dominant. These proteases may provide carbon and nitrogen sources to H8 by degrading proteins in the environment. This study will provide potential genetic information for the future research and development of cold-adapted proteases., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cell wall integrity (CWI) is crucial for fungal growth, pathogenesis, and adaptation to extracellular environments. Calcofluor white (CFW) is a cell wall perturbant that inhibits fungal growth, yet little is known about how phytopathogenic fungi respond to the CFW-induced stress., Results: In this study, we unveiled a significant discovery that CFW triggered the translocation of the transcription factor CgCrzA from the cytoplasm to the nucleus in Colletotrichum gloeosporioides. This translocation was regulated by an interacting protein, CgMkk1, a mitogen-activated protein kinase involved in the CWI pathway. Further analysis revealed that CgMkk1 facilitated nuclear translocation by phosphorylating CgCrzA at the Ser280 residue. Using chromatin immunoprecipitation sequencing, we identified two downstream targets of CgCrzA, namely CgCHS5 and CgCHS6, which are critical for growth, cell wall integrity, and pathogenicity as chitin synthase genes., Conclusions: These findings provide a novel insight into the regulatory mechanism of CgMkk1-CgCrzA-CgChs5/6, which enables response of the cell wall inhibitor CFW and facilitates infectious growth for C. gloeosporioides., (© 2024. The Author(s).)

Background: The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility., Objectives: This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility., Methods: A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package., Results: Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence., Conclusion: Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility., 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 Sun, Chen and Wang.)

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources., Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing., Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/μl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%., Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus., 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 Liu, Guo, Sun, Li, Liu, Chen, Wang, Wang, Li, Yao, Li and Pan.)

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K + channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mei-Ling Sun reports financial support was provided by Fundamental Research Funds for the Central Universities. Mei-Ling Sun reports financial support was provided by National Key Research and Development Program of China. Peng Wang reports financial support was provided by National Natural Science Foundation of China. Hui-hui Fu reports financial support was provided by National Natural Science Foundation of China. Chun-Yang Li reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 μg/mL) alleviated Aβ and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD., 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.)

Lithium-ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single-functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile-butyl hexafluoro methacrylate- poly (ethylene glycol) methacrylate- methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4-hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF- and Li 3 N-rich is formed at the cathode-electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm -2 , the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g -1 , with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium-metal batteries., (© 2024 Wiley-VCH GmbH.)

Efficient bifunctional hydrogen electrocatalysis, encompassing both hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR), is of paramount significance in advancing hydrogen-based societies. While non-precious-metal-based catalysts, particularly those based on nickel (Ni), are essential for alkaline HER/HOR, their intrinsic catalytic activity often falls short of expectations. Herein, an internal electric field (IEF) strategy is introduced for the engineering of heterogeneous nickel-vanadium oxide nanosheet arrays grown on porous nickel foam (Ni-V 2 O 3 /PNF) as bifunctional electrocatalysts for hydrogen electrocatalysis. Strikingly, the Ni-V 2 O 3 /PNF delivers 10 mA cm -2 at an overpotential of 54 mV for HER and a mass-specific kinetic current of 19.3 A g -1 at an overpotential of 50 mV for HOR, placing it on par with the benchmark 20% Pt/C, while exhibiting enhanced stability in alkaline electrolytes. Density functional theory calculations, in conjunction with experimental characterizations, unveil that the interface IEF effect fosters asymmetrical charge distributions, which results in more thermoneutral hydrogen adsorption Gibbs free energy on the electron-deficient Ni side, thus elevating the overall efficiency of both HER and HOR. The discoveries reported herein guidance are provided for further understanding and designing efficient non-precious-metal-based electrocatalysts through the IEF strategy., (© 2023 Wiley‐VCH GmbH.)

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75 T , was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75 T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75 T is affiliated with the genus Marinobacter . Strain ASW11-75 T showed highest 16S rRNA gene sequence similarity to ' Marinobacter arenosus ' CAU 1620 T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75 T and its closely related strains ( Marinobacter salarius R9SW1 T , Marinobacter similis A3d10 T , ' Marinobacter arenosus ' CAU 1620 T , Marinobacter sediminum R65 T , Marinobacter salinus Hb8 T , Marinobacter alexandrii LZ-8 T and Marinobacter nauticus ATCC 49840 T ) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C 16 : 0 , C 18 : 1  ω 9 c and C 16 : 0  N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75 T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75 T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75 T is proposed. The type strain is ASW11-75 T (=KCTC 82497 T =MCCC 1K05587 T ).

In contrast to the thermodynamically unfavorable anodic oxygen evolution reaction, the electrocatalytic urea oxidation reaction (UOR) presents a more favorable thermodynamic potential. However, the practical application of UOR has been hindered by sluggish kinetics. In this study, hierarchical porous nanosheet arrays featuring abundant Ni-WO 3 heterointerfaces on nickel foam (Ni-WO 3 /NF) is introduced as a monolith electrode, demonstrating exceptional activity and stability toward UOR. The Ni-WO 3 /NF catalyst exhibits unprecedentedly rapid UOR kinetics (200 mA cm -2 at 1.384 V vs. RHE) and a high turnover frequency (0.456 s -1 ), surpassing most previously reported Ni-based catalysts, with negligible activity decay observed during a durability test lasting 150 h. Ex situ X-ray photoelectron spectroscopy and density functional theory calculations elucidate that the WO 3 interface significantly modulates the local charge distribution of Ni species, facilitating the generation of Ni 3+ with optimal affinity for interacting with urea molecules and CO 2 intermediates at heterointerfaces during UOR. This mechanism accelerates the interfacial electrocatalytic kinetics. Additionally, in situ Fourier transform infrared spectroscopy provides deep insights into the substantial contribution of interfacial Ni-WO 3 sites to UOR electrocatalysis, unraveling the underlying molecular-level mechanisms. Finally, the study explores the application of a direct urea fuel cell to inspire future practical implementations., (© 2024 Wiley‐VCH GmbH.)

Objective: To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying molecular mechanisms., Methods: Cerebral IRI was induced in male Sprague-Dawley (SD) rats using middle cerebral artery occlusion (MCAO). The effects of PTX on cerebral ischaemia-reperfusion brain samples were detected through neurological deficit score, staining and electron microscopy; levels of ferroptosis biomarkers from brain samples were detected using kits. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), transferrin receptor protein 1, divalent metal transporter 1, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting., Results: Pre-treatment with PTX was found to improve neurological function, evidenced by reduced neurological deficit scores, decreased infarct volume and alleviated pathological features post-MCAO. This improvement was accompanied by reduced lipid peroxidation levels and mitigated mitochondrial damage. Notably, PTX's inhibitory effect on ferroptosis was characterised by enhanced Nrf2 nuclear translocation and regulation of ferroptosis-related proteins. Moreover, inhibition of Nrf2 using ML385 (an Nrf2-specific inhibitor) reversed PTX's neuroprotective effect on MCAO-induced ferroptosis via the SLC7A11/GPX4 signalling pathway., Conclusions: Ferroptosis is evident following cerebral ischaemia-reperfusion in rats. Pentoxifylline confers protection against IRI in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signalling 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 Second Hospital of Hebei Medical University. Published by Elsevier B.V. All rights reserved.)

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality., Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004)., Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p  < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p  = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p  = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p  = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p  = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p  = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p  = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p  = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p  = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p  = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p  = 0.008)., Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER., Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (C max ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for C max , 98.7% for AUC 0→t , 98.8% for AUC 0→∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356)., (© 2024, The American College of Clinical Pharmacology.)

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36 T , was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C 16:0 and summed feature 3 (C 16:1 ω7c and/or C 16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36 T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211 T (98.4%) and Alteromonas facilis P0213 T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36 T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36 T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36 T (= KCTC 82496 T  = MCCC 1K05585 T ). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl 2 addition. The draft genome of ASW11-36 T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Microbial cell factories have shown great potential for industrial production with the benefit of being environmentally friendly and sustainable. Yarrowia lipolytica is a promising and superior non-model host for biomanufacturing due to its cumulated advantages compared to model microorganisms, such as high fluxes of metabolic precursors (acetyl-CoA and malonyl-CoA) and its naturally hydrophobic microenvironment. However, although diverse compounds have been synthesized in Y. lipolytica cell factories, most of the relevant studies have not reached the level of industrialization and commercialization due to a number of remaining challenges, including unbalanced metabolic flux, conflict between cell growth and product synthesis, and cytotoxic effects. Here, various metabolic engineering strategies for solving the challenges are summarized, which is developing fast and extremely conducive to rational design and reconstruction of robust Y. lipolytica cell factories for advanced biomanufacturing. Finally, future engineering efforts for enhancing the production efficiency of this platform strain are highlighted.

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance., (© 2024. The Author(s).)

Piriformospora indica is an important endophytic fungus with broad potential for alleviating biotic and abiotic stress on host plants. This study monitored the growth dynamics of P. indica on five commonly used artificial media for microorganisms and analyzed its metabolic characteristics using Biolog Phenotype Microarray (PM) technology. The results showed that P. indica grew fastest on Potato Dextrose Agar (PDA), followed by Kidney Bean Agar (KBA), Alkyl Ester Agar (AEA), Oatmeal Agar (OA), and Luria-Bertani Agar (LB), and the most suitable medium for spore production was OA. Using Biolog PM1-10, 950 metabolic phenotypes of P. indica were obtained. P. indica could metabolize 87.89% of the tested carbon sources, 87.63% of the tested nitrogen sources, 96.61% of the tested phosphorus sources, and 100% of the tested sulfur sources. P. indica displayed 92 kinds of tested biosynthetic pathways, and it could grow under 92 kinds of tested osmotic pressures and 88 kinds of tested pH conditions. PM plates 1-2 revealed 43 efficient carbon sources, including M -Hydroxyphenyl acid, N -Acetyl- D -Glucosamine, Tyramine, Maltotrios, α -D -Glucosine, I -Erythritol, L -Valine, D -Melezitose, D -Tagatose, and Turanose. PM plates 3,6-8 indicated 170 efficient nitrogen sources, including Adenosine, Inosine Allantoin, D, L -Lactamide, Arg-Met, lle-Trp, Ala-Arg, Thr-Arg, Trp-Tyr, Val-Asn, Gly-Gly- D -Leu, Gly-Gly-Phe, and Leu-Leu-Leu. This study demonstrates that P. indica can metabolize a variety of substrates, such as carbon and nitrogen sources, and has a wide range of environmental adaptability. The growth dynamics on artificial culture media and metabolic phenotypes of P. indica can be used to investigate its biological characteristics, screen for more suitable growth and sporulation conditions, and elucidate the physiological mechanisms that enhance the stress resistance of host plants. This study provides a theoretical basis for its better application in agriculture., Competing Interests: C-yH was employed by Guizhou Provincial Tobacco Company. The remaining 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 Hu, Li, Wang, Sun, Huang and Wang.)

Hepatitis A virus (HAV) is mainly transmitted via contaminated food and water. HAV infection is a major global public health problem. Thus, developing a simple, rapid detection method is crucial for containing HAV epidemics, particularly in developing regions with limited laboratory resources. This study established a feasible HAV detection solution by combining reverse transcription multienzyme isothermal rapid amplification (RT-MIRA) and lateral flow dipstick (LFD) strips. Primers targeting the conserved 5'UTR sequence of HAV were used in the RT-MIRA-LFD assay. RNA extraction was enhanced by obtaining RNA directly from the centrifuged supernatant. Our study found that MIRA amplification could be finished in 12 min at 37 °C and naked-eye observation of the LFD strips in 10 min. The detection sensitivity of this method reached 1 copy/μl. RT-MIRA-LFD was compared to conventional RT-PCR using 35 human blood samples. The accuracy of the RT-MIRA-LFD method was 100%. The convenience, sensitivity, and rapidness of this detection method could provide a considerable advantage for diagnosing and controlling HAV infection, especially in regions with limited medical resources.

Treatment of irritable bowel syndrome (IBS) remains challenging for clinicians. Probiotic fungi may act as candidate options for IBS treatment, but systematic evaluation of their clinical value remains scarce. This study is aimed to assess the efficacy and the safety of probiotic fungi for IBS treatment by means of systematic review and meta-analysis. PubMed, Embase, Web of Science, and the Cochrane Library, were searched up to June 2022. Randomised controlled trials recruited subjects with prescriptions of probiotic fungi were eligible. Efficacy and safety of probiotic fungi were re-evaluated. Continuous data were pooled to obtain standardised difference in means (SMD) with a 95% confidence interval. The search strategy identified 120 articles of which 7 trial assessing 883 subjects were included in the analysis. Systematic data support that Saccharomyces helps to relieve abdominal pain/discomfort (SMD = -0.205, P = 0.005), and presented potential improvements on psychological outcomes, stool form for IBS patients. It is hard to demonstrate favourable effects on other symptoms (including distension, mucus passage, sense of incomplete evacuation, urgency, straining). The incidence of mild complications ranged from 0 to 51.4%, but no serious complications were observed in the included trials. Therefore, the partial response and the relative safe of probiotic fungi for IBS treatment have been demonstrated from the existing trials. However, it is premature to eventually declare the practical effects of probiotic fungi. Conducting more high-quality and large-scale trials and real-world studies, or even developing new fungal strains, is still necessary.

Background: Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae., Results: In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%., Conclusion: An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear., Objectives: To examine the efficacy and safety of PTPA in TA-PH., Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications., Results: Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I 2  = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I 2  = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100)., Conclusions: Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials., Registration: PROSPERO CRD42022354087., (© 2023 Wiley Periodicals LLC.)

Background: Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis., Methods: Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical., Results: Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study., Conclusion: The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population., (© 2023 The Author(s).)

Local ischemia in the cerebra leads to vascular injury and necrosis. Ferroptosis is involved in the pathophysiological process of many diseases and widely exists when ischemia-reperfusion injury occurs in many organs. The aim of this study was to evaluate the effect of Butylphthalide (NBP) on middle cerebral artery occlusion (MCAO) rats model-caused neuron injury. Sprague Dawley Rats were randomly allocated to receive sham and MCAO operation. NBP low-dose (40 mg/kg b.w), and high-dose (80 mg/kg b.w) were administrated in MACO rats. Results showed NBP improves infarct volume, attenuates neuronal apoptosis in the brain tissue of MCAO rats. The tumor necrosis factor (TNF-α), IL-6, and malondialdehyde (MDA) levels decreased after NBP administration, while the activity of superoxide dismutase (SOD) and the ratio of GSH/GSSG in MACO rats increased. MACO caused non-heme iron accumulation in the brain tissue and Perl's staining confirmed NBP attenuates ferroptosis in MACO rats. The protein expressions of SCL7A11 and glutathione peroxidase 4 (GPX4) decreased following MCAO, and NBP treatment subsequently increased the expression of SCL7A11 and GPX4. In vitro analysis in cortical neuron cells indicated that the GPX4 inhibitor reverses the inhibition of ferroptosis by NBP, which suggested that the SCL7A11/GPX4 pathway majorly contributed to the NBP ferroptosis protection effect.

Nitrogen (N) is an essential element for microbial growth and metabolism. The growth and reproduction of microorganisms in more than 75% of areas of the ocean are limited by N. Prochlorococcus is numerically the most abundant photosynthetic organism on the planet. Urea is an important and efficient N source for Prochlorococcus. However, how Prochlorococcus recognizes and absorbs urea still remains unclear. Prochlorococcus marinus MIT 9313, a typical Cyanobacteria, contains an ABC-type transporter, UrtABCDE, which may account for the transport of urea. Here, we heterologously expressed and purified UrtA, the substrate-binding protein of UrtABCDE, detected its binding affinity toward urea, and further determined the crystal structure of the UrtA/urea complex. Molecular dynamics simulations indicated that UrtA can alternate between "open" and "closed" states for urea binding. Based on structural and biochemical analyses, the molecular mechanism for urea recognition and binding was proposed. When a urea molecule is bound, UrtA undergoes a state change from open to closed surrounding the urea molecule, and the urea molecule is further stabilized by the hydrogen bonds supported by the conserved residues around it. Moreover, bioinformatics analysis showed that ABC-type urea transporters are widespread in bacteria and probably share similar urea recognition and binding mechanisms as UrtA from P. marinus MIT 9313. Our study provides a better understanding of urea absorption and utilization in marine bacteria., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in global sulfur and nutrient cycling, which is mainly produced by marine phytoplankton and macroalgae. Marinomonas algicola SM1966 T , a Gram-negative, aerobic and rod-shaped bacterium, was isolated from the surface of Ulva pertusa (Chlorophyta) algal sample collected off the coastal areas of Rongcheng, China. Here, we report the complete genome sequence of strain SM1966 T and its genomic characteristics to utilize DMSP, which may be produced by Ulva pertusa. The genome of strain SM1966 T contains one circular chromosome (4.3 Mbp) and one circular plasmid (149,271 bp). Genomic analysis showed that strain SM1966 T possesses a set of genes involved in DMSP transport, DMSP cleavage and the catabolism of acrylate, one product of DMSP cleavage. The results indicated that strain SM1966 T has the capacity to utilize DMSP and produce dimethyl sulfide (DMS), a volatile infochemical with important roles in global sulfur cycling. This study provides genetic insights into DMSP catabolism by algae-associated bacteria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA)., Methods: This prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi'an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery., Results: In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group., Conclusion: Continuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation., Trial Registration: This clinical trial was registered in the China Clinical Trials Center ( http://www.chictr.org.cn ) on 20/07/2020, with the registration number ChiCTR2000034821., (© 2023. The Author(s).)

Background: The effects of food on the pharmacokinetics and safety of metformin hydrochloride (MH) are unclear., Objective: To discover the effects of food on the pharmacokinetics and safety of MH, and its influence factors., Methods: English and Chinese databases, and grey (unpublished) literature were searched for eligible studies (registration No. CRD 42022321067 in PROSPERO network). The summary weighted mean difference for continuous variables, and the risk ratio for dichotomous variables was calculated for the main pharmacokinetic parameters. Heterogeneity among the included studies was analyzed using the I 2 test. Subgroup analyses, meta-regression, sensitivity analysis, and publication bias test were conducted., Results: Fourteen clinical trials were included, comprising 408 participants. The pooled AUC 0→t , AUC 0→∞ , and C max were decreased by about 30.21% ( I 2  = 16.7%, p = 0.276), 28.00% ( I 2  = 73.6%, p < 0.001), and 40.38% ( I 2  = 92.8%, p < 0.001). T max was delayed by about 29.42% ( I 2  = 45.1%, p = 0.034). Subgroup analysis and meta-regression analysis revealed dosage of MH and gender composition as two significant sources of heterogeneity in AUC 0→∞ and C max . Sensitivity analysis indicated that most of results were stable. The Egger's regression test and the Begg test (p > 0.05) confirmed that there is no publication bias., Conclusions: Pharmacokinetics parameters of MH were affected by food. High-fat, high-calorie diet lowered the extent and rate of absorption while slowing the absorption of metformin. These findings suggest that it is necessary to increase the dosage of MH in order to maintain the same treatment effect when administration of MH after a high fat, high calorie diet., Competing Interests: 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., (© 2023 The Authors.)

Hydrazine-assisted water electrolysis is a promising energy conversion technology for highly efficient hydrogen production. Rational design of bifunctional electrocatalysts, which can simultaneously accelerate hydrogen evolution reaction (HER)/hydrazine oxidation reaction (HzOR) kinetics, is the key step. Herein, we demonstrate the development of ultrathin P/Fe co-doped NiSe 2 nanosheets supported on modified Ni foam (P/Fe-NiSe 2 ) synthesized through a facile electrodeposition process and subsequent heat treatment. Based on electrochemical measurements, characterizations, and density functional theory calculations, a favorable "2 + 2" reaction mechanism with a two-step HER process and a two-step HzOR step was fully proved and the specific effect of P doping on HzOR kinetics was investigated. P/Fe-NiSe 2 thus yields an impressive electrocatalytic performance, delivering a high current density of 100 mA cm -2 with potentials of - 168 and 200 mV for HER and HzOR, respectively. Additionally, P/Fe-NiSe 2 can work efficiently for hydrazine-assisted water electrolysis and Zn-Hydrazine (Zn-Hz) battery, making it promising for practical application., (© 2023. The Author(s).)

Background: Emerging evidence supports shifting the focus from the quantity of macronutrients to quality to obtain greater benefits for the prognosis of ovarian cancer (OC). Additionally, despite the high relevance between macronutrient quality and quantity, the interaction of these parameters on OC survival remains unknown., Objective: A multidimensional macronutrient quality index (MQI) was applied to investigate the association between overall macronutrient quality and the survival of patients with OC., Methods: A prospective cohort study was conducted with 701 females diagnosed with OC who were enrolled from 2015 to 2020. Dietary intake information was obtained from a validated food frequency questionnaire. The MQI was calculated based on 3 quality indices: carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Cox proportional hazards regression was conducted to calculate HRs and 95% CIs. Furthermore, we evaluated whether energy intake status (total energy intake and energy balance) modified the association between MQI and OC survival., Results: During a median follow-up period of 38 (interquartile: 35-40) mo, 130 deaths occurred. The prediagnosis high MQI scores were associated with substantially improved survival among females with OC (HR tertile 3 vs. tertile 1 = 0.50, 95% CI: 0.33, 0.77). For sub-indices of the MQI, higher CQI (HR = 0.60, 95% CI: 0.36, 0.99), higher FQI (HR = 0.55, 95% CI: 0.34, 0.87), and higher PQI (HR = 0.58, 95% CI: 0.35, 0.94) scores were all associated with better survival. Notably, significant interactions were observed for the MQI score with total energy intake and energy balance as well as the quantity and quality of carbohydrates on survival., Conclusions: Intake of high-quality macronutrients before diagnosis was associated with improved survival among females with OC, especially for those with energy imbalance., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Bacillus cereus 2-6A, was isolated from the sediments in the hydrothermal area of the Pacific Ocean with a water depth of 2628 m. In this study, we report the whole genome sequence of strain 2-6A and analyze that to understand its metabolic capacities and biosynthesis potential of natural products. The genome of strain 2-6A consists of a circular chromosome of 5,191,018 bp with a GC content of 35.3 mol% and two plasmids of 234,719 bp and 411,441 bp, respectively. Genomic data mining reveals that strain 2-6A has several gene clusters involved in exopolysaccharides (EPSs) and polyhydroxyalkanoates (PHAs) production and complex polysaccharides degradation. It also possesses a variety of genes for allowing strain 2-6A to cope with osmotic stress, oxidative stress, heat shock, cold shock and heavy metal stress, which could play a vital role in the adaptability of the strain to hydrothermal environments. Gene clusters for secondary metabolite production, such as lasso peptide and siderophore, are also predicted. Therefore, genome sequencing and data mining provide insights into the molecular mechanisms of Bacillus in adapting to hydrothermal deep ocean environments and can facilitate further experimental exploration., Competing Interests: Declaration of Competing Interest The authors have no financial conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74 -/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PL PNs -dSTR FSIs ) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PL PNs -BLA PNs ) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity., (© 2023. The Author(s).)

Colletotrichum gloeosporioides , a significant fungal pathogen of crops and trees, causes large economic losses worldwide. However, its pathogenic mechanism remains totally unclear. In this study, four Ena ATPases ( Exitus natru -type adenosine triphosphatases), homology of yeast Ena proteins, were identified in C. gloeosporioides . Gene deletion mutants of Δ Cgena1 , Δ Cgena2 , Δ Cgena3 , and Δ Cgena4 were obtained through the method of gene replacement. First, a subcellular localization pattern indicated that CgEna1 and CgEna4 were localized in the plasma membrane, while the CgEna2 and CgEna3 were distributed in the endoparasitic reticulum. Next, it was found that CgEna1 and CgEna4 were required for sodium accumulation in C. gloeosporioides . CgEna3 was required for extracellular ion stress of sodium and potassium. CgEna1 and CgEna3 were involved in conidial germination, appressorium formation, invasive hyphal development, and full virulence. The mutant of Δ Cgena4 was more sensitive to the conditions of high concentrations of ion and the alkaline. Together, these results indicated that CgEna ATPase proteins have distinct roles in sodium accumulation, stress resistance, and full virulence in C. gloeosporioides .