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A plethora of CRISPR effectors, such as Cas3, Cas9, and Cas12a, are commonly employed as gene editing tools. Among these, Cas12 effectors developed based on Class II type V proteins exhibit distinct characteristics compared to Class II type VI and type II effectors, such as their ability to generate non-allelic DNA double-strand breaks, their compact structures, and the presence of a single RuvC-like nuclease domain. Capitalizing on these advantages, Cas12 family proteins have been increasingly explored and utilized in recent years. However, the characteristics and applications of different subfamilies within the type V protein family have not been systematically summarized. In this review, we focus on the characteristics of type V effector (CRISPR/Cas12) proteins and the current methods used to discover new effector proteins. We also summarize recent modifications based on engineering of type V effectors. In addition, we introduce the applications of type V effectors for gene editing in animals and plants, including the development of base editors, tools for regulating gene expression, methods for gene targeting, and biosensors. We emphasize the prospects for development and application of CRISPR/Cas12 effectors with the goal of better utilizing toolkits based on this protein family for crop improvement and enhanced agricultural production. [ABSTRACT FROM AUTHOR]

• XKC and luteolin could effectively alleviate the progression of Graves' disease(GD) by restoring the balance of Tfh/Tfr cells and reliving oxidative stress (OS). • Nrf2/HO-1 and PI3K/Akt signaling pathways are involved in the anti-GD process. • Luteolin is the main pharmacodynamic material basis for its therapeutic effect in anti-GD. The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS. [Display omitted] [ABSTRACT FROM AUTHOR]

The impact of early oral feeding after esophagectomy on brain-gut peptide secretion and gut function recovery has not been well investigated. This study aimed to fill this research gap. This study was based on a randomized clinical trial (ClinicalTrials.gov: NCT01998230). The patients in the early oral feeding group started oral food intake on postoperative day 1. In the late oral feeding group, nasogastric/nasoenteral feeding was applied from postoperative day 1 to 7, after which the patients began oral food intake. Serum brain-gut peptides were selected as the primary end points and tested before surgery and on postoperative days 1, 3, and 5. The time to first flatus and first defecation after surgery were evaluated. A total of 110 participants undergoing minimally invasive McKeown esophagectomy were prospectively included, with 63 patients in the early oral feeding group and 47 patients in the late oral feeding group. The distribution of clinicopathological characteristics was balanced between the 2 groups. Perioperative dynamic surveillance demonstrated higher serum concentrations of excitatory brain-gut peptides (gastrin P =.021, motilin P =.027, and substance-P P =.023) and lower serum concentrations of inhibitory brain-gut peptides (cholecystokinin P =.004 and somatostatin P =.019) in the early oral feeding group. Perioperative serum levels of brain-gut peptides correlated with postoperative early flatus and defecation. The multivariate analysis showed early oral feeding (versus late oral feeding) to be an independent predictive factor for early flatus and defecation (hazard ratio 2.40, P <.001; hazard ratio 2.73, P <.001, respectively). The early oral feeding program may accelerate the recovery of gut function by regulating brain-gut peptide secretion. Brain-gut peptides are possible treatment targets to improve early oral feeding benefits and promote personalized early oral feeding programs. [ABSTRACT FROM AUTHOR]

Transparent glass-ceramics based on ZnO–Al 2 O 3 –SiO 2 (ZAS) glass system exhibit excellent optical and mechanical properties that are dependent on crystal grains. Gahnite (ZnAl 2 O 4) was the main phase that crystallized in ZAS glass-ceramics via thermoelectric coupling treatment. The morphology and size of ZnAl 2 O 4 crystal were controlled by the electric field strength. Introduction of thermoelectric coupling field led to the refinement and dispersion of large and agglomerated ZnAl 2 O 4 crystal grains, which improved the transmission and Vickers' hardness of the ZAS-based glass-ceramics. Theoretical calculations revealed that crystal phase is the area of low electric field strength, which resulted in the migration of Zn ions (Zn2+) from glass phase to the ZnAl 2 O 4 crystal regions under the effect of thermoelectric coupling field. The decrease in the amount of Zn2+ in glass phase further limited its grain growth, and refinement of ZnAl 2 O 4 grains was achieved. This research shows an efficient and rapid approach to refine grains in ZAS glass-ceramics by application of thermoelectric coupling treatment. • In this work, it is the first time use of thermoelectric coupling field to precipitate ZnAl 2 O 4 nanocrystals in ZnO–Al 2 O 3 –SiO 2 glass-ceramics. • The application of a thermoelectric coupling field was used to refine and uniformly distribute ZnAl 2 O 4 crystals in ZnO–Al 2 O 3 –SiO 2 glass-ceramics. • The mechanism of a thermoelectric coupling field on crystal refinement is explained in detail, which provides ideas for the refinement and uniformly distribution of crystal grains. [ABSTRACT FROM AUTHOR]

The Li 2 O–Al 2 O 3 –SiO 2 (LAS) glass ceramics are prepared by one-step thermoelectric treatment. The influence of thermoelectric treatments on LAS glass-ceramics were studied. The crystal phase composition and microstructure of the LAS glass-ceramics were investigated by DSC, SEM, XRD and FTIR. Moreover, the thermal expansion performance and light transmittance of LAS nanocrystalline glass were characterized. The results show that low-expansion transparent LAS nanocrystalline glass can be produced in a short time by thermoelectric treatment. The free energy of nucleation and the degree of polymerization of the glass network are reduced by the electric field. The key is that the electric field polarizes Ti and Zr ions at the crystallization temperature, so that the crystal nuclei repel the same poles. This allows uniform crystal distribution, promotes crystallization and reduces one-step crystallization of crystal agglomeration. This proves that the rapid preparation of nanocrystalline glass by the one-step method is feasible, and provides a reference for the future one-step processing of glass-ceramics. • Thermoelectric treatment promotes crystallization in LAS nanocrystalline glass. • It eliminates crystal agglomeration in LAS nanocrystalline glass. • It can rapidly produce low-expansion transparent LAS nanocrystalline glass. [ABSTRACT FROM AUTHOR]

RNA N 6-methyladenosine (m6A) modification is implicated in cancer progression, yet its role in regulating long noncoding RNAs during cancer progression remains unclear. Here, we report that the m6A demethylase fat mass and obesity-associated protein (FTO) stabilizes long intergenic noncoding RNA for kinase activation (LINK-A) to promote cell proliferation and chemoresistance in esophageal squamous cell carcinoma (ESCC). Mechanistically, LINK-A promotes the interaction between minichromosome maintenance complex component 3 (MCM3) and cyclin-dependent kinase 1 (CDK1), increasing MCM3 phosphorylation. This phosphorylation facilitates the loading of the MCM complex onto chromatin, which promotes cell-cycle progression and subsequent cell proliferation. Moreover, LINK-A disrupts the interaction between MCM3 and hypoxia-inducible factor 1α (HIF-1α), abrogating MCM3-mediated HIF-1α transcriptional repression and promoting glycolysis and chemoresistance. These results elucidate the mechanism by which FTO-stabilized LINK-A plays oncogenic roles and identify the FTO/LINK-A/MCM3/HIF-1α axis as a promising therapeutic target for ESCC. [Display omitted] • FTO demethylates and stabilizes LINK-A in an m6A-dependent manner • LINK-A mediates MCM3 phosphorylation to facilitate cell-cycle progression • LINK-A sequesters HIF-1α from MCM3 to elicit its transcriptional activation • Targeting LINK-A sensitizes ESCC to cytotoxic chemotherapy Nan et al. reveal that the m6A demethylase FTO stabilizes LINK-A to confer ESCC progression and chemoresistance. LINK-A directly interacts with MCM3, promoting CDK1-mediated MCM3 phosphorylation and subsequent cell-cycle progression, as well as disrupting MCM3-mediated HIF-1α transcriptional suppression to trigger tumor glycolysis. [ABSTRACT FROM AUTHOR]

• An improved multi-timescale coordinated control strategy is proposed to be used in an integrated energy system. • A hybrid energy storage system is introduced into the system. • Operating costs and carbon emissions are considered as the optimization objectives. • General rules for sizing hybrid energy storage system are proposed in this paper. In view of the complex energy coupling and fluctuation of renewable energy sources in the integrated energy system, this paper proposes an improved multi-timescale coordinated control strategy for an integrated energy system (IES) with a hybrid energy storage system (HESS). The power response characteristics of various devices in IES at different time scales are analyzed which shows that the multi-timescale coordinated control method can be well coupled with the IES including HESS. The advantages of HESS over single energy storage system in stabilizing power fluctuation and extending energy storage life are compared and analyzed while the control method of supercapacitor under multi-time scale coordinated control strategy is proposed. The primary energy consumption, operating costs, carbon dioxide emissions and load shedding costs are considered the optimization objectives in the day-ahead rolling optimization stage according to the day-ahead forecast renewable energy (RE) data. In the intraday rolling adjusting stage, the proposed method can reduce the effect of the RE day-ahead forecasting errors to achieve the intraday energy scheduling balance and ensure the safe operation of the devices of IES. Considering the background of IES with a high proportion of renewable energy, this paper makes innovative use of the advantages of HESS to improve the power response characteristic of the system. The high-frequency part of RE is balanced by HESS in the real-time coordinated control stage. A typical structure of IES is applied and the simulation results are analyzed to show the performance of the proposed method in this paper. Moreover, general rules for sizing of HESS are also proposed. The influence of the hybrid energy storage capacity allocation ratio on battery capacity loss and carbon emission reduction is discussed. The Pareto front including the configuration and cost of supercapacitor has been obtained. As shown in the case, the application of HESS in the IES can improve the power response characteristic, extend the lithium-ion battery (LiB) life and has more benefits in reducing carbon emissions. [ABSTRACT FROM AUTHOR]

• PIV used to study flow fields & turbulence in 5x5 rod bundle across 22 cases (Reynolds: 310-12296). • Higher turbulence intensity at lower Reynolds due to significant relative velocity gradient in rod bundle. • Transition Reynolds ≈ 900 in rod bundle, less distinct than in pipes. • Fluctuation velocity decreases with Reynolds, abrupt rise at transition Reynolds. • Non-uniform transition Reynolds leads to varying turbulence intensity in rod bundle. Utilizing the particle image velocimetry (PIV) technique, this study investigates the fully developed flow field and turbulence statistics in a 5×5 rod bundle across 22 cases, with Reynolds numbers ranging from 310 to 12296.Time-averaged, statistical, and spectral analyses were performed on the full field and instantaneous velocity vectors obtained through PIV measurements to examine the velocity distribution, turbulence characteristics, and spectral features in different subchannels under various Reynolds numbers. In conjunction with a differential pressure transmitter, the flow properties and fluid transitions were also explored.The experimental results reveal that the relative velocity gradient in the rod bundle channel is more significant at lower Reynolds numbers. As the Reynolds number increases, the relative velocity distribution becomes more uniform. A comparison of experimental results from different planes indicates that the fluctuation velocity in the gap subchannel is greater than that in the inner subchannel, suggesting that tightly arranged rods can generate higher turbulence intensity. Furthermore, the transition observed through the friction factor in the rod bundle channel is less distinct than those in pipes, with the transition Reynolds number being approximately 900. A low Reynolds number effect is present in the rod bundle channel, where the dimensionless fluctuation velocity decreases as the Reynolds number increases. Upon reaching the transition Reynolds number, the area-averaged dimensionless fluctuation velocity abruptly rises. By examining the turbulence intensity variations at different positions within the rod bundle, it becomes evident that the transition Reynolds numbers vary across different subchannel positions. Ultimately, the experimental data can be employed to validate the applicability of turbulence models for different Reynolds numbers. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest digestive tract cancer with poor prognosis. In our previous comprehensive genomics study, we identified that hotspot mutations in the solute carrier family 35 member E2 (SLC35E2) promoter region was significantly associated with worse prognosis in patients with ESCC. However, the biological function and molecular mechanism of SLC35E2 remains unclear. This study was to investigate the malignant function and mechanism of SLC35E2 in ESCC. Western blotting and qRT-PCR were used to assess the expression of SLC35E2 in ESCC cell lines. Luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to assess the transcriptional inhibition of KLF4. Incucyte cell proliferation assay, colony formation assay and subcutaneous tumor formation in nude mice were used to assess the malignant function of SLC35E2. SLC35E2 can promote ESCC cell proliferation in vitro and in vivo. Krüppel-like factor 4 (KLF4), a transcriptional repressor in ESCC, binds to the SLC35E2 promoter and represses the expression of SLC35E2. The transcriptional suppression of KLF4 can be blocked by the mutation at −118 site of the SLC35E2 promoter. Besides, the accumulation of SLC35E2 expression contributes to the malignant phenotype of ESCC. These results indicate that SLC35E2 may be used as a biomarker for prognosis as well as a therapeutic target for patients with ESCC. [ABSTRACT FROM AUTHOR]