Emerging insights into Lipocalin-2: Unraveling its role in Parkinson's Disease.

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, marked by a complex pathogenesis. Lipocalin-2 (LCN2) emerges as a crucial factor during the progression of PD. Belonging to the lipocalin family, LCN2 is integral to several biological functions, including glial cell activation, iron homeostasis regulation, immune response, inflammatory reactions, and oxidative stress mitigation. Substantial research has highlighted marked increases in LCN2 expression within the substantia nigra (SN), cerebrospinal fluid (CSF), and blood of individuals with PD. This review focuses on the pathological roles of LCN2 in neuroinflammation, aging, neuronal damage, and iron dysregulation in PD. It aims to explore the underlying mechanisms of LCN2 in the disease and potential therapeutic targets that could inform future treatment strategies.

Alkenyl oxindole is a novel PROTAC moiety that recruits the CRL4DCAF11 E3 ubiquitin ligase complex for targeted protein degradation.

Alkenyl oxindoles have been characterized as autophagosome-tethering compounds (ATTECs), which can target mutant huntingtin protein (mHTT) for lysosomal degradation. In order to expand the application of alkenyl oxindoles for targeted protein degradation, we designed and synthesized a series of heterobifunctional compounds by conjugating different alkenyl oxindoles with bromodomain-containing protein 4 (BRD4) inhibitor JQ1. Through structure-activity relationship study, we successfully developed JQ1-alkenyl oxindole conjugates that potently degrade BRD4. Unexpectedly, we found that these molecules degrade BRD4 through the ubiquitin-proteasome system, rather than the autophagy-lysosomal pathway. Using pooled CRISPR interference (CRISPRi) screening, we revealed that JQ1-alkenyl oxindole conjugates recruit the E3 ubiquitin ligase complex CRL4DCAF11 for substrate degradation. Furthermore, we validated the most potent heterobifunctional molecule HL435 as a promising drug-like lead compound to exert antitumor activity both in vitro and in a mouse xenograft tumor model. Our research provides new employable proteolysis targeting chimera (PROTAC) moieties for targeted protein degradation, providing new possibilities for drug discovery.

N-C QDs coated with a molecularly imprinted polymer as a fluorescent probe for detection of penicillin.

Many diseases are due to bacterial infections, which are treated by penicillin. Existing methods for penicillin detection have relatively high requirements for sample storage and processing, personnel professionalism, and instruments. Herein, water-soluble N-C quantum dots (QDs) from wheat straw were synthesized in a green way by using an efficient and simple method. The N-C QDs were modified with an imprinted layer by a gel-sol method. Penicillin selectively quenched the fluorescence emission of N-C QDs@MIP, and a linear relationship was obtained in the concentration range of 1.0 × 10-6-15.2 × 10-6 mol L-1. The reliability of the sensor in real sample analysis was satisfactory with results in the range of 93.6%-100%, and the sensor showed good reproducibility and long-term stability. The study provides a simple strategy to fabricate N-C QDs@MIP with a highly selective recognition ability and opens an avenue to develop highly efficient sensing probes for the detection of antibiotics in biological applications.

Enhanced TiO2/SiCx Active Layer Formed In Situ on Coal Gangue/Ti3C2 MXene Electrocatalyst as Catalytic Integrated Units for Efficient Li-O2 Batteries.

The pursuit of efficient cathode catalysts to improve cycle stability at ultra-high rates plays an important role in boosting the practical utilization of Li-O2 batteries. Featured as industrial solid waste, coal gangue with rich electrochemical active components could be a promising candidate for electrocatalysts. Here, a coal gangue/Ti3C2 MXene hybrid with a TiO2/SiCx active layer is synthesized and applied as a cathode catalyst in Li-O2 batteries. The coal gangue/Ti3C2 MXene hybrid has a tailored amorphous/crystalline heterostructure, enhanced active TiO2 termination, and a stable SiCx protective layer; thereby, it achieved an excellent rate stability. The Li-O2 battery, assembled with a coal gangue/Ti3C2 MXene cathode catalyst, was found to obtain a competitive full discharge capacity of 3959 mAh g-1 and a considerable long-term endurance of 180 h (up to 175 cycles), with a stable voltage polarization of 1.72 V at 2500 mA g-1. Comprehensive characterization measurements (SEM, TEM, XPS, etc.) were applied; an in-depth analysis was conducted to reveal the critical role of TiO2/SiCX active units in regulating the micro-chemical constitution and the enhanced synergistic effect between coal gangue and Ti3C2 MXene. This work could provide considerable insights into the rational design of catalysts derived from solid waste gangue for high-rate Li-O2 batteries.

Genome-wide identification and expression analysis of the WNK kinase gene family in soybean.

WNK kinases are a unique class of serine/threonine protein kinases that lack a conserved catalytic lysine residue in the kinase domain, hence the name WNK (with no K, i.e., lysine). WNK kinases are involved in various physiological processes in plants, such as circadian rhythm, flowering time, and stress responses. In this study, we identified 26 WNK genes in soybean and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, cis-regulatory elements, expression patterns, and conserved protein motifs. The soybean WNK genes were unevenly distributed on 15 chromosomes and underwent 21 segmental duplication events during evolution. We detected 14 types of cis-regulatory elements in the promoters of the WNK genes, indicating their potential involvement in different signaling pathways. The transcriptome database revealed tissue-specific and salt stress-responsive expression of WNK genes in soybean, the second of which was confirmed by salt treatments and qRT-PCR analysis. We found that most WNK genes were significantly up-regulated by salt stress within 3 h in both roots and leaves, except for WNK5, which showed a distinct expression pattern. Our findings provide valuable insights into the molecular characteristics and evolutionary history of the soybean WNK gene family and lay a foundation for further analysis of WNK gene functions in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01440-5.

Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats.

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

Multi-omic approaches provide insights into the molecular mechanisms of Sojae semen germinatum water extract against overactive bladder.

Sojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCß2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.

Soybean reduced internode 1 determines internode length and improves grain yield at dense planting.

Major cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2-GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean-maize intercropping systems.

A signal recognition particle receptor gene from the sea cucumber, Apostichopus japonicas.

The signal recognition particle (SRP) system delivers approximately 30% of the proteome to the endoplasmic reticulum (ER) membrane. SRP receptor alpha (SRα) binds to SRP for targeting nascent secreted proteins to the ER membrane in eukaryotic cells. In this study, the SRα homologous gene was identified in the sea cucumber, Apostichopus japonicus (AjSRα). AjSRα codes for 641 amino acids and has 54.94% identity with its mammalian homologs. Like mammalian SRα, it is expected to contain the SRP-alpha N domain, SRP54_N domain, and SRP54 domain. In addition, AjSRα is ubiquitously expressed in adult tissues and exhibits a sexually dimorphic expression pattern, with significantly higher expression in ovaries compared to testes. As a maternal factor, AjSRα can be continuously detected during embryonic development. Importantly, we first attempted to investigate its function by using lentiviral vectors for delivering SRα gene-specific shRNA, and we revealed that lentiviral vectors do not induce an upregulation of immune-related enzymes in sea cucumbers. However, compared to the dsRNA-based RNA interference (RNAi) method, lentivirus-mediated RNAi caused dynamic changes in gene expression at a later time. This study supplied the technical support for studying the functional mechanism of SRα in sea cucumbers.

Cushioning Performance of the Biomimetic Cobweb Cushioning Silicone Pad.

At present, the packing method of "plastic bag-buffer packing-packing paper box" is adopted for bearing packaging. However, the common packing method has a poor packing effect and poor versatility. In this study, a new biomimetic cobweb cushion is proposed to solve the problem of insufficient cushioning capacity of high-precision bearing cushion packaging pads. First, according to the nature of cobweb form, the cobweb cushion structure configuration is determined. Next, based on the structure of the cushion and the relationship between the parameters of radial thread and spiral thread, a mechanical and target optimization model is established. The stress nephogram of bearing and the cobweb cushion are analyzed under three drop heights of 381, 610, and 700 mm, in the finite element simulation software to ensure that the maximum bearings stress is not beyond the material yield strength. Via the 3D printing technology, a cobweb cushion shell cast is made. Drop tests of the bearing were performed, and the results were verified with the finite element simulation analysis. This research can provide technical support for the protection of high-precision bearings from accidental drops during transportation.

Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform.

Background and Purpose: A recently developed biology-guided radiotherapy platform, equipped with positron emission tomography (PET) and computed tomography (CT), provides both anatomical and functional image guidance for radiotherapy. This study aimed to characterize performance of the kilovoltage CT (kVCT) system on this platform using standard quality metrics measured on phantom and patient images, using CT simulator images as reference. Materials and Methods: Image quality metrics, including spatial resolution/modular transfer function (MTF), slice sensitivity profile (SSP), noise performance and image uniformity, contrast-noise ratio (CNR) and low-contrast resolution, geometric accuracy, and CT number (HU) accuracy, were evaluated on phantom images. Patient images were evaluated mainly qualitatively. Results: On phantom images the MTF10% is about 0.68 lp/mm for kVCT in PET/CT Linac. The SSP agreed with nominal slice thickness within 0.7 mm. The diameter of the smallest visible target (1% contrast) is about 5 mm using medium dose mode. The image uniformity is within 2.0 HU. The geometric accuracy tests passed within 0.5 mm. Relative to CT simulator images, the noise is generally higher and the CNR is lower in PET/CT Linac kVCT images. The CT number accuracy is comparable between the two systems with maximum deviation from the phantom manufacturer range within 25 HU. On patient images, higher spatial resolution and image noise are observed on PET/CT Linac kVCT images. Conclusions: Major image quality metrics of the PET/CT Linac kVCT were within vendor-recommended tolerances. Better spatial resolution but higher noise and better/comparable low contrast visibility were observed as compared to a CT simulator when images were acquired with clinical protocols.

Genome-Wide Identification and Characterization of the Soybean Snf2 Gene Family and Expression Response to Rhizobia.

Sucrose nonfermenting 2 (Snf2) family proteins are the core component of chromatin remodeling complexes that can alter chromatin structure and nucleosome position by utilizing the energy of ATP, playing a vital role in transcription regulation, DNA replication, and DNA damage repair. Snf2 family proteins have been characterized in various species including plants, and they have been found to regulate development and stress responses in Arabidopsis. Soybean (Glycine max) is an important food and economic crop worldwide, unlike other non-leguminous crops, soybeans can form a symbiotic relationship with rhizobia for biological nitrogen fixation. However, little is known about Snf2 family proteins in soybean. In this study, we identified 66 Snf2 family genes in soybean that could be classified into six groups like Arabidopsis, unevenly distributed on 20 soybean chromosomes. Phylogenetic analysis with Arabidopsis revealed that these 66 Snf2 family genes could be divided into 18 subfamilies. Collinear analysis showed that segmental duplication was the main mechanism for expansion of Snf2 genes rather than tandem repeats. Further evolutionary analysis indicated that the duplicated gene pairs had undergone purifying selection. All Snf2 proteins contained seven domains, and each Snf2 protein had at least one SNF2_N domain and one Helicase_C domain. Promoter analysis revealed that most Snf2 genes had cis-elements associated with jasmonic acid, abscisic acid, and nodule specificity in their promoter regions. Microarray data and real-time quantitative PCR (qPCR) analysis revealed that the expression profiles of most Snf2 family genes were detected in both root and nodule tissues, and some of them were found to be significantly downregulated after rhizobial infection. In this study, we conducted a comprehensive analysis of the soybean Snf2 family genes and demonstrated their responsiveness to Rhizobia infection. This provides insight into the potential roles of Snf2 family genes in soybean symbiotic nodulation.

Turn "Waste" Into Wealth: MoO2 @coal Gangue Electrocatalyst with Amorphous/Crystalline Heterostructure for Efficient Li-O2 Batteries.

Unreasonable accumulation of coal gangue in mining area has become the major source of global pollution. Probing the high-valued utilization of coal gangue has become a key approach to address the problem. Herein, a promising catalyst of MoO2 @coal gangue with amorphous/crystalline heterostructure derived from mine solid waste, which acts as an efficient cathode for Li-O2 batteries is first reported. Impressively, the as-prepared catalyst exhibits a favorable initial discharge capacity of 9748 mAh g-1 and promising long-term cyclic stability over 2200 h. Experimental results coupled with density functional theory (DFT) analysis reveal that the synergistic interaction between high-activity MoO2 and stable SiO2 , unique amorphous/crystalline heterostructure and the modified interfacial adsorption of LiO2 intermediate are critical factors in promoting the electrochemical performance. This work provides a new insight to design marked electrocatalysts by mine solid waste for Li-O2 batteries.

Identification and functional analysis of Dmrt1 gene and the SoxE gene in the sexual development of sea cucumber, Apostichopus japonicus.

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.

Physicochemical Synergistic Separator Coating Induces Uniform and Rapid Deposition of Li and Zn Ions.

Li and Zn metal batteries are the most promising candidates to replace conventional Li-ion batteries. However, a series of issues, especially dendrites caused by uneven deposition of cations during charge-discharge cycles, hinder their practical application. Here, we proposed a facile separator modification method which combines physical and chemical forces to regulate uniform and rapid deposition of both Li+ and Zn2+. Physically, the electronegativity of modified separators drives rapid transport of metal ions via a surface diffusion mode. Chemically, the polar surface functional groups on coated separators induce uniform deposition of metal ions so that the dendrite growth is effectively inhibited. As a result, the Li and Zn metal anodes employing modified separators can cycle stably for over 1000 h under a large current density of 10 mA cm-2.

Sexually dimorphic expression of foxl2 in the sea urchin (Mesocentrotus nudus).

Sea urchin (Mesocentrotus nudus) is an important economically mariculture species in several Asian countries, and gonads are the sole edible parts for people. In addition to commercial value, it is an excellent model for studying gonadal development, sex determination and sex differentiation. Identify sex-related genes is an effective way to reveal the molecular mechanism of gonadal development. In the present study, the foxl2 homologous gene was identified in M. nudus. Foxl2 is not a maternal factor, and is detected for the first time in two-arm stages. Additionally, the expression of foxl2 in the testis is higher than in the ovaries at the same developmental stages. The foxl2 transcripts were specifically enriched in the cytoplasm of germ cellsboth in the ovary and testis, but their proteins were more concentrated in the area near the oocyte nucleus. Overall, this study contributes to our understanding of the dynamic and sexually dimorphic expression pattern of foxl2 and provide a useful germ cell marker during gametogenesis in sea urchin.

Production, purification, and functional properties of microbial fibrinolytic enzymes produced by microorganism obtained from soy-based fermented foods: developments and challenges.

According to the World Health Organization, cardiovascular disease (CVD) has become a major cause of chronic illness around the globe. It has been reported that soy-based fermented food (SFF) is very effective in preventing thrombus (one of the most important contributing factors to CVD), which are mainly attributed to the bioactive substances, especially the fibrinolytic enzymes (FE) generated by microorganisms during the fermentation process of soybean food. This paper therefore mainly reviewed the microbial fibrinolytic enzymes (MFE) from SFF. We first discuss the use of microbial fermentation to produce FE, with an emphasis on the strains involved. The production, purification, physicochemical properties, structure-functional attributes, functional properties and possible application of MFE from SFF are then discussed. Finally, current limitations and future perspectives for the production, purification, and the practical application of MFE are discussed. MFE from SFF pose multiple health benefits, including thrombolysis, antihypertension, anti-inflammatory, anti-hyperlipidemia, anticancer, neuroprotective, antiviral and other activities. Therefore, they exhibit great potential for functional foods and nutraceutical applications, especially foods with CVDs prevention potential.

Plasma Surface Engineering of NiCo2S4@rGO Electrocatalysts Enables High-Performance Li-O2 Batteries.

The sluggish redox reaction kinetics for aprotic Li-O2 batteries (LOBs) caused by the insulating discharge product of Li2O2 could result in the poor round-trip efficiency, low rate capability, and cyclic stability. To address these challenges, we herein fabricated NiCo2S4 supported on reduced graphene oxide (NiCo2S4@rGO), the surface of which is further modified via a unique low-pressure capacitive-coupled nitrogen plasma (CCPN-NiCo2S4@rGO). The high ionization environment of the plasma could etch the surface of NiCo2S4@rGO, introducing effective nitrogen doping. The as-prepared CCPN-NiCo2S4@rGO has been employed as an efficient catalyst for advanced LOBs. The electrochemical analysis, combined with theoretical calculations, reveals that the N-doping can effectively improve the thermodynamics and kinetics for LiO2 adsorption, giving rise to a well-knit Li2O2 formation on CCPN-NiCo2S4@rGO. The LOBs based on the CCPN-NiCo2S4@rGO oxygen electrode deliver a low overpotential of 0.75 V, a high discharge capacity of 10,490 mA h g-1, and an improved cyclic stability (more than 110 cycles). This contribution may pave a promising avenue for facile surface engineering of the electrocatalyst in LOBs and other energy storage systems.

RAF22, ABI1 and OST1 form a dynamic interactive network that optimizes plant growth and responses to drought stress in Arabidopsis.

Plants adapt to their ever-changing environment via positive and negative signals induced by environmental stimuli. Drought stress, for instance, induces accumulation of the plant hormone abscisic acid (ABA), triggering ABA signal transduction. However, the molecular mechanisms for switching between plant growth promotion and stress response remain poorly understood. Here we report that RAF (rapidly accelerated fibrosarcoma)-LIKE MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 22 (RAF22) in Arabidopsis thaliana physically interacts with ABA INSENSITIVE 1 (ABI1) and phosphorylates ABI1 at Ser416 residue to enhance its phosphatase activity. Interestingly, ABI1 can also enhance the activity of RAF22 through dephosphorylation, reciprocally inhibiting ABA signaling and promoting the maintenance of plant growth under normal conditions. Under drought stress, however, the ABA-activated OPEN STOMATA1 (OST1) phosphorylates the Ser81 residue of RAF22 and inhibits its kinase activity, restraining its enhancement of ABI1 activity. Taken together, our study reveals that RAF22, ABI1, and OST1 form a dynamic regulatory network that plays crucial roles in optimizing plant growth and environmental adaptation under drought stress.