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This study examines the effects of magnetic-field-dependent (MFD) viscosity on the boundary layer flow of a non-Newtonian sodium alginate-based Fe3O4 nanofluid over an impermeable stretching surface. The non-Newtonian Casson and homogeneous nanofluid models are utilized to derive the governing flow and heat transfer equations. Applying Lie group transformations to dimensional partial differential equations yields nondimensional ordinary differential equations, which are then numerically solved using the spectral quasi-linearization technique. The analysis primarily focuses on the impacts of the MFD viscosity parameter, nanoparticle volume fraction of Fe3O4, and magnetic parameters on the flow and heat transfer characteristics. The local skin friction and heat transfer rate behaviors influenced by viscosity changes due to the magnetic field are discussed. It is found that MFD viscosity significantly impacts flow and thermal energies, enhancing skin friction coefficients and reducing Nusselt numbers in the boundary layer region.

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During transcription-coupled DNA repair (TCR) the detection of DNA damage and initiation of nucleotide excision repair (NER) is performed by translocating RNA polymerases (RNAP), which are arrested upon encountering bulky DNA lesions. Two opposing models of the subsequent steps of TCR in bacteria exist. In the first model, stalled RNAPs are removed from the damage site by recruitment of Mfd which dislodges RNAP by pushing it forwards before recruitment of UvrA and UvrB. In the second model, UvrD helicase backtracks RNAP from the lesion site. Recent studies have proposed that both UvrD and UvrA continuously associate with RNAP before damage occurs, which forms the primary damage sensor for NER. To test these two models of TCR in living E. coli, we applied super-resolution microscopy (PALM) combined with single particle tracking to directly measure the mobility and recruitment of Mfd, UvrD, UvrA, and UvrB to DNA during ultraviolet-induced DNA damage. The intracellular mobilities of NER proteins in the absence of DNA damage showed that most UvrA molecules could in principle be complexed with RNAP, however, this was not the case for UvrD. Upon DNA damage, Mfd recruitment to DNA was independent of the presence of UvrA, in agreement with its role upstream of this protein in the TCR pathway. In contrast, UvrD recruitment to DNA was strongly dependent on the presence of UvrA. Inhibiting transcription with rifampicin abolished Mfd DNA-recruitment following DNA damage, whereas significant UvrD, UvrA, and UvrB recruitment remained, consistent with a UvrD and UvrA performing their NER functions independently of transcribing RNAP. Together, although we find that up to ∼8 UvrD-RNAP-UvrA complexes per cell could potentially form in the absence of DNA damage, our live-cell data is not consistent with this complex being the primary DNA damage sensor for NER.

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The accurate identification of drug-protein interactions (DPIs) is crucial in drug development, especially concerning G protein-coupled receptors (GPCRs), which are vital targets in drug discovery. However, experimental validation of GPCR-drug pairings is costly, prompting the need for accurate predictive methods. To address this, we propose MFD-GDrug, a multimodal deep learning model. Leveraging the ESM pretrained model, we extract protein features and employ a CNN for protein feature representation. For drugs, we integrated multimodal features of drug molecular structures, including three-dimensional features derived from Mol2vec and the topological information of drug graph structures extracted through Graph Convolutional Neural Networks (GCN). By combining structural characterizations and pretrained embeddings, our model effectively captures GPCR-drug interactions. Our tests on leading GPCR-drug interaction datasets show that MFD-GDrug outperforms other methods, demonstrating superior predictive accuracy.

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The acquisition of high quality lyophilized IgY products, characterized by an aesthetically pleasing visage, heightened stability, and a marked preservation of activity, constitutes an indispensable pursuit in augmenting the safety and pragmatic utility of IgY. Within this context, an exploration was undertaken to investigate an innovative modality encompassing microwave freeze-drying (MFD) as a preparatory methodology of IgY. Morphological assessments revealed that both cryogenic freezing and subsequent MFD procedures resulted in aggregation of IgY, with the deleterious influence posed by the MFD phase transcending that of the freezing phase. The composite protective agent comprised of trehalose and mannitol engendered a safeguarding effect on the structural integrity of IgY, thereby attenuating reducing aggregation between IgY during the freeze-drying process. Enzyme-linked immunosorbent assay (ELISA) outcomes demonstrated a discernible correlation between IgY aggregation and a notable reduction in its binding affinity towards the pertinent antigen. Comparative analysis vis-à-vis the control sample delineated that when the trehalose-to-mannitol ratio was upheld at 1:3, a two-fold outcome was achieved: a mitigation of the collapse susceptibility within the final product as well as a deterrence of IgY agglomeration, concomitant with an elevated preservation rate of active antibodies (78.57 %).

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Chongqing, as the last ecological barrier of the Upper Yangtze River, is constrained to achieve "dual carbon" goals due to imbalanced energy structure. Based on selecting the energy structure influencing factors through Copula function and Granger causality, a multi-dimensional dynamic support vector machine model (SSA-MFD-SVR-ARIMA) by adopting sparrow algorithm was constructed to predict the proportion of Chongqing's energy structure from 2021 to 2030 under the drive of green finance development, and an optimization path was obtained. The novel findings confirm that (1) the correlated contribution rate of Green Finance to optimizing Chongqing's Energy Structure is 10.8 %; (2) under the sustained growth rate of Green Finance at 4.5 %, the proportion of coal consumption will reach 40.03 % by 2030, and non-fossil energy consumption will account for 27 %. It confirms that Chongqing can achieve the Energy Development Plan assigned by the Central Government in 2025. The research proposes a four-dimensional optimized pathway from a financial perspective that includes green equity investments, digital finance for energy, financing environmental rights and interests, and developing an industry fund. Furthermore, our put forward the safeguard strategies for financing, innovation, linkage, and protection mechanisms of this pathway optimization.

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Transcription-coupled repair (TCR), discovered as preferential nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers located in transcribed mammalian genes compared to those in nontranscribed regions of the genome, is defined as faster repair of the transcribed strand versus the nontranscribed strand in transcribed genes. The phenomenon, universal in model organisms including Escherichia coli, yeast, Arabidopsis, mice, and humans, involves a translocase that interacts with both RNA polymerase stalled at damage in the transcribed strand and nucleotide excision repair proteins to accelerate repair. Drosophila, a notable exception, exhibits TCR but lacks an obvious TCR translocase. Mutations inactivating TCR genes cause increased damage-induced mutagenesis in E. coli and severe neurological and UV sensitivity syndromes in humans. To date, only E. coli TCR has been reconstituted in vitro with purified proteins. Detailed investigations of TCR using genome-wide next-generation sequencing methods, cryo-electron microscopy, single-molecule analysis, and other approaches have revealed fascinating mechanisms.

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In this research paper, the generalized projective Riccati equations method (GPREM) is applied successfully to procure the soliton solutions of the local M-fractional longitudinal wave equation (LWE) arising in mathematical physics with dispersion caused by the transverse Poisson's effect in a magneto-electro-elastic circular rod (MEECR). Applying a wave transformation to the local M-fractional LWE, the equation can be turned into a set of algebraic equations. Solving the algebraic equation system, we procure the soliton solutions of the local M-fractional LWE. Both the obtained solution functions in the study and the graphical simulations depicted for these functions. It will assist researchers working in this field in the physical interpretation of this equation. Moreover, the reported solutions propose a rich platform to examine the local M-fractional LWE.

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The preparation of egg yolk powder (EYP) with excellent solubility and high retention of active IgY is of great significance for increasing the added value and promoting the application of EYP. A new method of preparing EYP by microwave-assisted freeze-drying (MFD) was researched. Confocal laser scanning microscopy results demonstrated that the supplementation of excipients (sucrose, trehalose, and maltodextrin) could inhibit lipoproteins aggregation in egg yolk induced by freezing. Scanning electron microscopy indicated that drying further damaged the structure of lipoproteins in EYP, leading to lipid separation from it. FTIR and fluorescence spectra confirmed this finding, indicating that excipients enhance protein stability. Compared with conventional freeze-drying (FD), EYP prepared by MFD, particularly that containing excipients, had higher solubility (63 g/100 g), active antibody retention rate and shorter drying time. Therefore, excipients can significantly improve the solubility and stability of EYP and the retention rate of active IgY.

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BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

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Keratin-associated proteins (KAPs) are a structural component of cashmere fibers and in part determine fiber attributes. The gene encoding the high-glycine/tyrosine KAP6-2 (called KRTAP6-2) has been described in sheep, but it has not been identified goats. In this study, a 252-bp open reading frame with similarity to ovine KRTAP6-2 was found on goat chromosome 1, with its upstream and downstream flanking sequences are closely related with ovine KRTAP6-2 but are clearly distinct from other ovine KRTAP6-n sequences. Polymerase chain reaction amplification followed by single strand conformation polymorphism analysis of this region revealed five distinct banding patterns representing five different sequences (A to E) in 230 Longdong cashmere goats. Eleven diallelic single nucleotide polymorphisms (SNPs), a three-nucleotide sequence variation, and a 12-bp insertion/deletion were found among these five sequences, with most SNPs being either outside the coding region or synonymous. The presence of variant D was found to be associated with decreased mean fiber diameter (MFD; present: 13.26 ± 0.07 µm; absent: 13.55 ± 0.04 µm; p < 0.001), suggesting that variation in KRTAP6-2 may affect fiber diameter and have value as a molecular marker for improving the cashmere fiber diameter trait.

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Moral psychology is a domain that deals with moral identity, appraisals and emotions. Previous work has primarily focused on moral development and the associated role of culture. Knowing that language is an inherent element of a culture, we used the social media platform Twitter to compare moral behaviors of Japanese tweets with English tweets. The five basic moral foundations, i.e., Care, Fairness, Ingroup, Authority, and Purity, along with the associated emotional valence were compared between English and Japanese tweets. The tweets from Japanese users depicted relatively higher Fairness, Ingroup, and Purity, whereas English tweets expressed more positive emotions for all moral dimensions. Considering moral similarities in connecting users on social media, we quantified homophily concerning different moral dimensions using our proposed method. The moral dimensions Care, Authority, and Purity for English and Ingroup, Authority and Purity for Japanese depicted homophily on Twitter. Overall, our study uncovers the underlying cultural differences with respect to moral behavior in English- and Japanese-speaking users.

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Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-ß, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia.

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HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC (21c) comprising a VHL ligand conjugated to lovastatin acid that potently degrades HMGCR in Insig-silenced HepG2 cells (DC50 = 120 nmol/L) and forms a stable ternary complex, as predicated by a holistic modeling protocol. Most importantly, oral administration of the corresponding lactone 21b reveled favorable plasma exposures referring to both the parent 21b and the conversed acid 21c. Further in vivo studies of 21b demonstrated robust HMGCR degradation and potent cholesterol reduction in mice with diet-induced hypercholesterolemia, highlighting a promising strategy for treating hyperlipidemia and associated diseases.

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The mfd (mutation frequency decline) gene was identified by screening an auxotrophic Escherichia coli strain exposed to UV and held in a minimal medium before plating onto rich or minimal agar plates. It was found that, under these conditions, holding cells in minimal (nongrowth) conditions resulted in mutations that enabled cells to grow on minimal media. Using this observation as a starting point, a mutant was isolated that failed to mutate to auxotrophy under the prescribed conditions, and the gene responsible for this phenomenon (mutation frequency decline) was named mfd. Later work revealed that mfd encoded a translocase that recognizes a stalled RNA polymerase (RNAP) at damage sites and binds to the stalled RNAP, recruits the nucleotide excision repair damage recognition complex UvrA2UvrB to the site, and facilitates damage recognition and repair while dissociating the stalled RNAP from the DNA along with the truncated RNA. Recent single-molecule and genome-wide repair studies have revealed time-resolved features and structural aspects of this transcription-coupled repair (TCR) phenomenon. Interestingly, recent work has shown that in certain bacterial species, mfd also plays roles in recombination, bacterial virulence, and the development of drug resistance.

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis with millions of deaths annually, remains one of the most formidable pathogen to global public health. As the most successful intracellular pathogens, Mtb can spatiotemporally coordinate the transcription and translation timely to reconcile the inevitable transcription-replication conflicts. Mutation frequency decline (Mfd) is a bacterial ATP-dependent DNA translocase that couples DNA repair to transcription via hydrolyzing ATP as energy, which preferentially acts on the damaged DNA transcribed strand to rescue stalled RNAP or dissociate RNAP to terminate the transcription depending on impediment severity, mitigating the damage to bacteria. In addition to the traditional damage repair effect, Mfd may also promote bacteria mutagenesis under stresses and boost the drug resistance. Mfd is widespread among bacteria and intensively studied, but there are very few studies in Mycobacteria, especially Mtb. In this review, the structure, function and mechanism characteristics of Mfd in Mtb (MtbMfd, Rv1020) are explored, with emphasis on the regulatory network of MtbMfd and its potential as a prime target for antibiotic drugs against tuberculosis.

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Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). Below, we discuss the architecture of key proteins in bacterial NER and recent biochemical, structural and single-molecule studies that shed light on the lesion recognition steps of both the GGR and the TCR sub-pathways. Although a great deal has been learned about both of these sub-pathways, several important questions, including damage discrimination, roles of ATP and the orchestration of protein binding and conformation switching, remain to be addressed.

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Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair (NER) that preferentially removes lesions from the template-strand (t-strand) that stall RNA polymerase (RNAP) elongation complexes (ECs). Mfd mediates TCR in bacteria by removing the stalled RNAP concealing the lesion and recruiting Uvr(A)BC. We used cryo-electron microscopy to visualize Mfd engaging with a stalled EC and attempting to dislodge the RNAP. We visualized seven distinct Mfd-EC complexes in both ATP and ADP-bound states. The structures explain how Mfd is remodeled from its repressed conformation, how the UvrA-interacting surface of Mfd is hidden during most of the remodeling process to prevent premature engagement with the NER pathway, how Mfd alters the RNAP conformation to facilitate disassembly, and how Mfd forms a processive translocation complex after dislodging the RNAP. Our results reveal an elaborate mechanism for how Mfd kinetically discriminates paused from stalled ECs and disassembles stalled ECs to initiate TCR.

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RNA polymerase (RNAP) encounters various roadblocks during transcription. These obstacles can impede RNAP movement and influence transcription, ultimately necessitating the activity of RNAP-associated factors. One such factor is the bacterial protein Mfd, a highly conserved DNA translocase and evolvability factor that interacts with RNAP. Although Mfd is thought to function primarily in the repair of DNA lesions that stall RNAP, increasing evidence suggests that it may also be important for transcription regulation. However, this is yet to be fully characterized. To shed light on Mfd's in vivo functions, we identified the chromosomal regions where it associates. We analyzed Mfd's impact on RNAP association and transcription regulation genome-wide. We found that Mfd represses RNAP association at many chromosomal regions. We found that these regions show increased RNAP pausing, suggesting that they are hard to transcribe. Interestingly, we noticed that the majority of the regions where Mfd regulates transcription contain highly structured regulatory RNAs. The RNAs identified regulate a myriad of biological processes, ranging from metabolism to transfer RNA regulation to toxin-antitoxin (TA) functions. We found that cells lacking Mfd are highly sensitive to toxin overexpression. Finally, we found that Mfd promotes mutagenesis in at least one toxin gene, suggesting that its function in regulating transcription may promote evolution of certain TA systems and other regions containing strong RNA secondary structures. We conclude that Mfd is an RNAP cofactor that is important, and at times critical, for transcription regulation at hard-to-transcribe regions, especially those that express structured regulatory RNAs.

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Objective To study the constitutive model of adipose tissue at medium strain rate and its parameter inversion. Methods Based on experiments of adipose tissue mechanical properties, the compression experiment of adipose tissues was reconstructed by finite element method, and the parameters for characterizing constitutive models of adipose tissues were screened. Combined with the method of feasible direction (MFD) in optimization method, the reverse calculation for parameters of fat tissue constitutive model at medium strain rate was conducted. ResultsCompared with Ogden constitutive model, the viscoelastic constitutive model was more suitable for characterizing the mechanical response at medium strain rate (260 s-1). The parameters of the constitutive model suitable for simulation were obtained using the reverse method. Conclusions The viscoelastic constitutive model was more suitable for characterizing the mechanical response at medium strain rate. The results provide references for studying the influence of human adipose tissues on body injury in finite element simulation of vehicle collisions.

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In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11-13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24-32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

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