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In order to find new potential fungicides and anticancer agents, a series of new coumarin amide derivatives bearing fluorine were synthesized and characterized spectroscopically. Compounds A6, B11, C2 and C7 were confirmed by X-ray diffraction further. The antifungal bioassays against five typical pathogenic fungi showed that compound C5 exhibited more remarkable fungicidal activities against Alternaria alternata (EC50 = 11.5 μg/mL), Colletotrichum gloeosporioides (EC50 = 18.0 μg/mL), Pyricularia grisea (EC50 = 33.8 μg/mL), surpassing kresoxim-methyl. Molecular docking result indicated that C5 displayed high binding affinity to chitinase, which plays crucial role in degradation and remodeling of fungal cell walls. In addition, the anticancer bioassays against three cancer cells demonstrated that compound A4 displayed excellent growth inhibitory effect against Hela cells with IC50 value of 8.13 μM, and low cytotoxicity against human normal cells BEAS-2B. Flow cytometric analysis further demonstrated that A4 significantly arrested cell cycle at the S phase and trigger apoptosis. With the above interesting biological profile, these coumarin derivatives could be used as anfungicides and anticancer candidates.

Abstract Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS–based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post–projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 35 external calibrants to eliminate the impact of LC setups on projection accuracy. Results showed that post–projection calibration consistently achieved a median projection error below 3.2% of the elution time. The ranking results of putative candidates reached similar levels among different CMs. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.

Abstract Nonconventional luminescent materials have been rising stars in organic luminophores due to their intrinsic characteristics, including water‐solubility, biocompatibility, and environmental friendliness and have shown potential applications in diverse fields. As an indispensable branch of nonconventional luminescent materials, polysiloxanes, which consist of electron‐rich auxochromic groups, have exhibited outstanding photophysical properties due to the unique silicon atoms. The flexible Si‐O bonds benefit the aggregation, and the empty 3d orbitals of Si atoms can generate coordination bonds including N → Si and O → Si, altering the electron delocalization of the material and improving the luminescent purity. Herein, we review the recent progress in luminescent polysiloxanes with different topologies and discuss the challenges and perspectives. With an emphasis on the driving force for the aggregation and the mechanism of tuned emissions, the role of Si atoms played in the nonconventional luminophores is highlighted. This review may provide new insights into the design of nonconventional luminescent materials and expand their further applications in sensing, biomedicine, lighting devices, etc.

Summary: Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

Traditional drilling methods often face difficulty meeting the demand for efficient and accurate coring under complex geological conditions. Cordless coring is an advanced technology that uses hydraulic lifting to carry out coring, which can achieve automation and automated and intelligent drilling operations. In this research, a new type of hydraulic lifting cordless coring drilling tool is designed. Moreover, a numerical simulation model of the fluid flow in the annulus between the spearhead and spool of the cordless coring drilling tool was established. Orthogonal simulation tests are carried out, and according to the orthogonal test data, a numerical prediction model of the spool annulus fluid field based on the Backpropagation Neural Network (BP neural network) is established. The prediction of the flow rate of the drilling fluid and the spool back-pressure ratio was obtained when the structural parameters of the spearhead and the spool annulus were different. A multi-objective optimization of the annulus flow structure of the cordless core drilling tool has been carried out. The optimization objectives include deciding the back pressure ratio of the spool overcoming the spring and the flow rate of the drilling fluid. According to the established nonlinear optimization model and based on the improved Non-dominated Sorting Genetic Algorithm II (NSGA-II) multi-objective optimization algorithm, it is verified that the convergence speed and diversity of the improved algorithm are better than those before the improvement. The simulation and experimental validation are carried out. It is verified that the flow rate of drilling fluid increased by 33.56% after optimization, and the force ratio was lowered by 5.825%. Finally, based on the simulation and optimization results, the φ96 cordless core drilling tool was manufactured on a trial basis, and on-site concrete drilling, coring, and hydraulic lifting operations were conducted for smooth coring and lifting. This study could provide an important scientific basis and technical support for the application and development of hydraulic lifting cordless coring technology.

Workover operations significantly impact the service life and gas production capacity of coalbed methane (CBM) wells and are crucial for optimizing resource exploitation. To investigate workover operations’ impact on coal seam reservoirs, the authors designed a series of experiments and obtained the following results: (1) The workover operation induced a phase transition in the solid-liquid composition produced by the CBM well, indicating changes in the coal reservoir’s internal structure. (2) During the stable production stage before and after the workover, the proportion of Na+, Cl−, Ca2+, and Total Dissolved Solids (TDS) in the water samples showed a downward trend as a whole, while the HCO3−; after the workover, the Na+, Cl−, Ca2+, and TDS all increased suddenly, while the HCO3− decreased. (3) While inorganic minerals predominated in the precipitation material during the stable production stage pre-workover, their proportion decreased post-workover, with a noticeable shift in their qualitative composition. (4) It is an indisputable fact that workover operations cause physical and chemical damage to coal seam reservoirs. During workover operation, how to avoid damage and conduct benign reconstruction to the reservoir will be the direction of our future efforts. The experimental results provide valuable insights that can guide the optimization of CBM workover operations and inform the strategic planning of subsequent drainage activities.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age globally. Emerging evidence suggests that the dysregulation of microRNAs (miRNAs) and gut dysbiosis are linked to the development of PCOS. In this study, the effects of Lacticaseibacillus paracasei subsp. paracasei DSM 27449 (DSM 27449) were investigated in a rat model of PCOS induced by letrozole. The administration of DSM 27449 resulted in improved ovarian function, reduced cystic follicles, and lower serum testosterone levels. Alterations in miRNA expressions and increased levels of the pro-apoptotic protein Bax in ovarian tissues were observed in PCOS-like rats. Notably, the administration of DSM 27449 restored the expression of miRNAs, including miR-30a-5p, miR-93-5p, and miR-223-3p, leading to enhanced ovarian function through the downregulation of Bax expressions in ovarian tissues. Additionally, 16S rRNA sequencing showed changes in the gut microbiome composition after letrozole induction. The strong correlation between specific bacterial genera and PCOS-related parameters suggested that the modulation of the gut microbiome by DSM 27449 was associated with the improvement of PCOS symptoms. These findings demonstrate the beneficial effects of DSM 27449 in ameliorating PCOS symptoms in letrozole-induced PCOS-like rats, suggesting that DSM 27449 may serve as a beneficial dietary supplement with the therapeutic potential for alleviating PCOS.

This study investigated the characteristics and sources of heavy metal(loid) pollution in the soil of a key industrial park in Kunming, China. In total, 60 soil samples (40 from agricultural land and 20 from construction land) were collected from and around the park. The soil pH and contents of Arsenic (As), lead (Pb), copper (Cu), zinc (Zn), cadmium (Cd), mercury (Hg), nickel (Ni), and chromium (Cr) were measured. The contents of the eight heavy metal(loid)s were analyzed using the background values of heavy metal(loid)s in the Kunming soil. The pollution load, geoaccumulation, and Nemero Comprehensive Pollution Indices were used for environmental risk evaluation. Cluster and principal component analyses were used to resolve heavy metal(loid) sources. Cd was enriched in construction and agricultural soils. As, Hg, Cd, Pb, Cu, and Zn exhibited large spatial differentiation and were significantly affected by the external environment. A regional pollution load index of 3.02 indicated overall heavy pollution. The pollution load index for each heavy metal(loid) indicated light pollution. The geoaccumulation index indicated relatively severe As, Cd, Cu, Pb, and Zn pollution. The Nemero Composite Pollution Index value showed that the study area was heavily polluted, with construction land being mildly polluted by Cd, and agricultural land being moderately polluted. The results of the spatial distribution show that there were high levels of contamination in the center. Correlation and principal component analyses showed that the pollution sources of the eight heavy metal(loid)s varied. Hg, Cd, and Pb originate primarily from industrial and agricultural pollution. Traffic sources significantly impacted Cu, Pb, Cd, and Cr. Natural sources are the main sources of Cr, Ni, and Cd. Ni is also affected by industrial sources, whereas Zn and Cu are affected by agricultural pollution. The influences of As, Cd, and Pb on the surface soil in the study area were more serious. Cd is more widely polluted and should be a priority in controlling soil heavy metal(loid)s.

The Dlk1-Dio3 domain is important for normal embryonic growth and development. The heart is the earliest developing and functioning organ of the embryo. In this study, we constructed a transcriptional termination model by inserting termination sequences and clarified that the lack of long non-coding RNA (lncRNA) expression in the Dlk1-Dio3 domain caused the death of maternal insertion mutant (MKI) and homozygous mutant (HOMO) mice starting from E13.5. Parental insertion mutants (PKI) can be born and grow normally. Macroscopically, dying MKI and HOMO embryos showed phenomena such as embryonic edema and reduced heart rate. Hematoxylin and eosin (H.E.) staining showed thinning of the myocardium in MKI and HOMO embryos. In situ hybridization (IHC) and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) showed downregulation of lncGtl2, Rian, and Mirg expression in MKI and HOMO hearts. The results of single-cell RNA sequencing (scRNA-Seq) analysis indicated that the lack of lncRNA expression in the Dlk1-Dio3 domain led to reduced proliferation of epicardial cells and may be an important cause of cardiac dysplasia. In conclusion, this study demonstrates that Dlk1-Dio3 domain lncRNAs play an integral role in ventricular development.

Due to the increase in nanoplastics (NPs) abundance in aquatic environments, their effects on phytoplankton have aroused large research attention. In this study, 100 nm sized polystyrene NPs were chosen to investigate their effecting performance and mechanisms on a typical dinoflagellates Alexandrium tamarense. The results indicated the population growth and photosynthetic efficiencies of A. tamarense were significantly inhibited by NPs exposure, as well as the increase in cellular total carotenoids and paralytic shellfish toxins (PSTs). Meanwhile, the cellar ROS levels increased, corresponding to the increased activities or contents of multiple antioxidant components, including SOD, CAT, GPX, GR, GSH and GSSG. The transcriptional results support the physiological–biochemical results and further revealed the down-regulation of genes encoding the light reaction centers (PSI and PSII) and up-regulation of genes encoding the antioxidant components. Up-regulation of genes encoding key enzymes of the Calvin cycle and glycolytic pathway together with the TCA cycle could accelerate organic carbon and ATP production for A. tamarense cells resistant to NPs stress. Finally, more Glu and acetyl-CoA produced by the enhanced GSH cycle and the glycolytic pathway, respectively, accompanied by the up-regulation of Glu and Arg biosynthesis genes supported the increase in the PST contents under NPs exposure. This study established a data set involving physiological–biochemical changes and gene information about marine dinoflagellates responding to NPs, providing a data basis for further evaluating the ecological risk of NPs in marine environments.

Functional molecules have been attracting increasing attention in environmental and physiological studies. In particular, folic acid (FA) could be considered a key factor in estimating, adjusting, and making decisions in the treatment of neurodevelopmental disorders. It promotes the general significance and conceptual for considering FA molecular scientific research detections, which implies related advancement in both of biological structure and detection methods. Among these applications, the FA molecule acts as a coenzyme that incorporates carbon atoms and synthesizes purines and pyrimidines. Therefore, the calibration method has real applications and can be used as a sensing platform and for detection approaches, which conveys the internal relationship between the FA molecule and physiological characterization. This mini review briefly discusses multiple FA application fields and detection pathways and could supplement their utilization in anticipation of the onset of disease.

Hypolipidemic and hepatoprotective effectives of the newly synthesized guaiacol-based fibrate derivatives were evaluated in Triton WR-1339-induced hyperlipidemic mice. All the target compounds were preliminary screened, in which compound T5 showed significant hypolipidemic effects, decreasing triglycerides (TG) and total cholesterol (TC), which was better than the positive drug clofibrate. Furthermore, compound T5 has a dose-dependent effect on the blood lipid lowering activity of hyperlipidemia mice, and hepatic transaminases (AST and ALT) induced by hyperlipidemia have a significant improvement effect. Histological examination of the liver of hyperlipidemic mice supplemented with T5 revealed a significant amelioration in hepatic lipid accumulation when compared with the effect of the positive drug clofibrate. The mechanism of lipid-lowering showed that T5 could significantly increase the expression of PPAR-α protein in the liver of hyperlipidemic mice. In addition, T5 can also improve the lipid peroxidation process induced by hyperlipidemia, reducing the level of malondialdehyde (MDA). These findings reinforced the effects of T5 as a hypolipidemic candidate compound with liver protective activity.

To discover novel and effective potential anticancer agents, a series of azophenol derivatives containing 1,3,4-oxadiazoles moiety was synthesized and investigated for their anticancer activities against several human cancer cell lines by MTT method. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS spectral analyses. Among the prepared compounds, 5df displayed significant anti-proliferative activity against HCT116 cancer cells with an IC50 value of 4.09 ± 0.04 µM. Moreover, this compound had low cytotoxicity against normal cells. Flow cytometric analysis indicated that compound 5df arrested the cell cycle at S phase and induced apoptosis in a dose-dependent manner. Additionally, network pharmacology analysis calculated that 5df might target several key proteins, including AKT serine/threonine kinase 1 (AKT1), SRC proto-oncogene, non-receptor tyrosine kinase (SRC). Furthermore, molecular docking study indicated that 5df exhibited potentially high binding affinity to these target proteins with binding energies lower than −8 kcal/mol. These findings provide valuable insights for the development of azophenol derivatives as potential anticancer agents.

Research has been conducted on the (2S,3R)-3-hydroxy-3-methylproline. The enantioselective synthesis of this compound has been carried out via the Sharpless AD reaction and the results indicate that the route has good enantiomeric purity and high yield.

Abstract 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) is a key enzyme in the shikimate pathway for the biosynthesis of aromatic compounds. L-Phe and L-Tyr bind to the two main DAHPS isoforms and inhibit their enzyme activities, respectively. Synthetic biologists aim to relieve such inhibitions in order to improve the productivity of aromatic compounds. In this work, we reported a point mutant of yeast DHAPS, Aro3D154N, which retains the wild type enzyme activity but converts it highly inert to the inhibition by L-Phe. The Aro3 crystal structure along with the molecular dynamics simulations analysis suggests that the D154N mutation distant from the inhibitor binding cavity may reduce the binding affinity of L-Phe. Growth assays demonstrated that substitution of the conserved D154 with asparagine suffices to relieve the inhibition of L-Phe on Aro3, L-Tyr on Aro4, and the inhibitions on their corresponding homologues from diverse yeasts. The importance of our discovery is highlighted by the observation of 29.1% and 43.6% increase of yield for the production of tyrosol and salidroside respectively upon substituting ARO3 with ARO3 D154N . We anticipate that this allele would be used broadly to increase the yield of various aromatic products in metabolically diverse microorganisms.

Carrier-based Unmanned Aerial Vehicle (CUAV) landing is an extremely critical link in the overall chain of CUAV operations on ships. Vision-based landing location methods have advantages such as low cost and high accuracy. However, when an aircraft carrier is at sea, it may encounter complex weather conditions such as haze, which could lead to vision-based landing failures. This paper proposes a runway line recognition and localization method based on haze removal enhancement to solve this problem. Firstly, a haze removal algorithm using a multi-mechanism, multi-architecture network model is introduced. Compared with traditional algorithms, the proposed model not only consumes less GPU memory but also achieves superior image restoration results. Based on this, We employed the random sample consensus method to reduce the error in runway line localization. Additionally, extensive experiments conducted in the Airsim simulation environment have shown that our pipeline effectively addresses the issue of decreased detection accuracy of runway line detection algorithms in haze maritime conditions, improving the runway line localization accuracy by approximately 85%.

Spermidine is well known to accumulate in plants exposed to drought, but the regulatory network associated with its biosynthesis and accumulation and the underlying molecular mechanisms remain unclear. Here, we demonstrated that the Trifolium repens TrMYB33 relayed the ABA signal to modulate drought-induced spermidine production by directly regulating the expression of TrSAMS1, which encodes an S-adenosylmethionine synthase. This gene was identified by transcriptome and expression analysis in T. repens. TrSAMS1 overexpression and its pTRV-VIGS-mediated silencing demonstrated that TrSAMS1 is a positive regulator of spermidine synthesis and drought tolerance. TrMYB33 was identified as an interacting candidate through yeast one-hybrid library screening with the TrSAMS1 promoter region as the bait. TrMYB33 was confirmed to bind directly to the predicted TAACCACTAACCA (the TAACCA MYB binding site is repeated twice in tandem) within the TrSAMS1 promoter and to act as a transcriptional activator. Additionally, TrMYB33 contributed to drought tolerance by regulating TrSAMS1 expression and modulating spermidine synthesis. Additionally, we found that spermidine accumulation under drought stress depended on ABA and that TrMYB33 coordinated ABA-mediated upregulation of TrSAMS1 and spermidine accumulation. This study elucidated the role of a T. repens MYB33 homolog in modulating spermidine biosynthesis. The further exploitation and functional characterization of the TrMYB33–TrSAMS1 regulatory module can enhance our understanding of the molecular mechanisms responsible for spermidine accumulation during drought stress.

Ensuring precise segmentation of colorectal polyps holds critical importance in the early diagnosis and treatment of colorectal cancer. Nevertheless, existing deep learning-based segmentation methods are fully supervised, requiring extensive, precise, manual pixel-level annotation data, which leads to high annotation costs. Additionally, it remains challenging to train large-scale segmentation models when confronted with limited colonoscopy data. To address these issues, we introduce the general segmentation foundation model—the Segment Anything Model (SAM)—into the field of medical image segmentation. Fine-tuning the foundation model is an effective approach to tackle sample scarcity. However, current SAM fine-tuning techniques still rely on precise annotations. To overcome this limitation, we propose WSPolyp-SAM, a novel weakly supervised approach for colonoscopy polyp segmentation. WSPolyp-SAM utilizes weak annotations to guide SAM in generating segmentation masks, which are then treated as pseudo-labels to guide the fine-tuning of SAM, thereby reducing the dependence on precise annotation data. To improve the reliability and accuracy of pseudo-labels, we have designed a series of enhancement strategies to improve the quality of pseudo-labels and mitigate the negative impact of low-quality pseudo-labels. Experimental results on five medical image datasets demonstrate that WSPolyp-SAM outperforms current fully supervised mainstream polyp segmentation networks on the Kvasir-SEG, ColonDB, CVC-300, and ETIS datasets. Furthermore, by using different amounts of training data in weakly supervised and fully supervised experiments, it is found that weakly supervised fine-tuning can save 70% to 73% of annotation time costs compared to fully supervised fine-tuning. This study provides a new perspective on the combination of weakly supervised learning and SAM models, significantly reducing annotation time and offering insights for further development in the field of colonoscopy polyp segmentation.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

High-mobility group B (HMGB) proteins are a class of non-histone proteins associated with eukaryotic chromatin and are known to regulate a variety of biological processes in plants. However, the functions of HMGB genes in tomato (Solanum lycopersicum) remain largely unexplored. Here, we identified 11 members of the HMGB family in tomato using BLAST. We employed genome-wide identification, gene structure analysis, domain conservation analysis, cis-acting element analysis, collinearity analysis, and qRT-PCR-based expression analysis to study these 11 genes. These genes were categorized into four groups based on their unique protein domain structures. Despite their structural diversity, all members contain the HMG-box domain, a characteristic feature of the HMG superfamily. Syntenic analysis suggested that tomato SlHMGBs have close evolutionary relationships with their homologs in other dicots. The promoter regions of SlHMGBs are enriched with numerous cis-elements related to plant growth and development, phytohormone responsiveness, and stress responsiveness. Furthermore, SlHMGB members exhibited distinct tissue-specific expression profiles, suggesting their potential roles in regulating various aspects of plant growth and development. Most SlHMGB genes respond to a variety of abiotic stresses, including salt, drought, heat, and cold. For instance, SlHMGB2 and SlHMGB4 showed positive responses to salt, drought, and cold stresses. SlHMGB1, SlHMGB3, and SlHMGB8 were involved in responses to two types of stress: SlHMGB1 responded to drought and heat, while SlHMGB3 and SlHMGB8 responded to salt and heat. SlHMGB6 and SlHMGB11 were solely regulated by drought and heat stress, respectively. Under various treatment conditions, the number of up-regulated genes significantly outnumbered the down-regulated genes, implying that the SlHMGB family may play a crucial role in mitigating abiotic stress in tomato. These findings lay a foundation for further dissecting the precise roles of SlHMGB genes.

This study investigated the effects of rumen bypass dandelion extract on the lactation performance, immune index, and mammary oxidative stress of lactating dairy cows fed a high-concentrate diet. This study used a complete randomized block design, and initial milk production, somatic cell counts, and parities were set as block factors. Sixty Holstein cows with similar health conditions and lactating periods (70 ± 15 d) were divided into three groups with 20 replicates per group. The treatments included the LCD group (low-concentrate diet, concentrate–forage = 4:6), HCD group (high-concentrate group, concentrate–forage = 6:4), and DAE group (dandelion aqueous extract group, HCD group with 0.5% DAE). The experimental period was 35 d, and cows were fed three times in the morning, afternoon, and night with free access to water. The results showed the following: (1) Milk production in the HCD and DAE groups was significantly higher (p < 0.05) than that in the LCD group from WK4, and the milk quality differed during the experimental period. (2) The HCD group’s pH values significantly differed (p < 0.01) from those of the LCD and DAE groups. (3) In WK2 and WK4 of the experimental period, the somatic cell counts of dairy cows in the HCD group were significantly higher (p < 0.05) than those in the DAE group. (4) The serum concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and protein carbonyl (PC) in the HCD group were significantly higher (p < 0.05) than those in the LCD group. The activity of catalase (CAT) in the LCD and DAE groups was stronger (p < 0.01) than that in the HCD group. (5) The correlation analysis revealed significantly positive correlations between the plasma LPS concentration and serum concentrations of 8-OHdG (p < 0.01), PC (p < 0.01), and malondialdehyde (MDA, p < 0.05) and significantly negative correlations (p < 0.01) between the plasma LPS concentration and activities of CAT and superoxide dismutase. (6) Compared with that in the HCD and DAE groups, the mRNA expression of α, β, and κ casein and acetyl CoA carboxylase in bovine mammary epithelial cells was significantly higher (p < 0.05) in the LCD group, and the mRNA expression of fatty acid synthetase and stearoyl CoA desaturase in the LCD group was significantly higher (p < 0.01) than that in the HCD group. (7) Compared with that in the LCD and HCD groups, the mRNA expression of Nrf2 was significantly higher (p < 0.01) in the DAE group, and the mRNA expression of cystine/glutamate transporter and NAD (P) H quinone oxidoreductase 1 in the DAE group was significantly higher (p < 0.05) than that in the HCD group. Overall, feeding a high-concentrate diet could increase the milk yield of dairy cows, but the milk quality, rumen homeostasis, and antioxidative capability were adversely affected. The supplementation of DAE in a high-concentrate diet enhanced antioxidative capability by activating the Nrf2 regulatory factor and improved rumen homeostasis and production performance.

Nanoparticles (NPs) have been surfacing as a pivotal platform for vaccine development. In our previous work, we developed a cholera toxin B subunit (CTB)-based self-assembled nanoparticle (CNP) and produced highly promising bioconjugate nanovaccines by loading bacterial polysaccharide (OPS) in vivo. In particular, the Klebsiella pneumoniae O2 serotype vaccine showcased a potent immune response and protection against infection. However, extremely low yields limited its further application. In this study, we prepared an efficient Klebsiella pneumoniae bioconjugate nanovaccine in Escherichia coli with a very high yield. By modifying the 33rd glycine (G) in the CNP to aspartate (D), we were able to observe a dramatically increased expression of glycoprotein. Subsequently, through a series of mutations, we determined that G33D was essential to increasing production. In addition, this increase only occurred in engineered E. coli but not in the natural host K. pneumoniae strain 355 (Kp355) expressing OPSKpO2. Next, T-cell epitopes were fused at the end of the CNP(G33D), and animal experiments showed that fusion of the M51 peptide induced high antibody titers, consistent with the levels of the original nanovaccine, CNP-OPSKpO2. Hence, we provide an effective approach for the high-yield production of K. pneumoniae bioconjugate nanovaccines and guidance for uncovering glycosylation mechanisms and refining glycosylation systems.

Abstract A series of new π‐conjugated macrocycles (AzoM‐n‐E, n = 1–3) incorporating azobenzene units have been synthesized by a facile strategy in one‐pot reaction. The resultant azobenzene‐embedded macrocycles feature intrinsic photoresponsive behaviors and intriguing supramolecular assembling properties. The smallest macrocycle AzoM‐1‐E with a rigid planar conjugated backbone structure is used to prepare the single crystal transistors, showing reversible optical tunability. The moderate size macrocycle AzoM‐2‐E assembles into a dimer in the form of interpenetration through π‐π stacking between azobenzene units. The largest macrocycle AzoM‐3‐E with enhanced flexibility can adaptively assemble with various types of electron‐deficient guests accompanied by distortion of azobenzene. Typically, AzoM‐3‐E assembles with the planar F4‐TCNQ to form a tetragonal geometry by C‐F···π and π‐π interactions, while the assembly with ellipsoidal C70 via π‐π interactions induces AzoM‐3‐E to form a boat‐shaped geometry. This work will shed new light on the development of functional conjugated macrocycles in organic electronics.

Abstract Complete skin reconstruction is a hierarchical, physiological assembly process involving healing of the epidermis, dermis, vasculature, nerves, and cutaneous appendages. To date, few works have reported complete skin regeneration, particularly lacking vascular structures and hair follicles after full skin defects. In this study, a hydrogel derived from the skin secretion of Andrias davidianus (SSAD) that features adhesiveness was used as a bioactive scaffold to load micronized amnion (MA). The SSAD hydrogel was found to promote the migration and proliferation of amnion stem cells and human keratinocytes, as well as inhibit their apoptosis in vitro. In a rat full‐skin defect model, the regeneration of skin appendages was observed at the wound area, achieving scarless healing. Transcriptome analyses further validated that SSAD could positively regulate cell migration, proliferation, and differentiation. These functions might be attributed to the abundant growth factors present in the SSAD. Synergized by the delivery of MA, SSAD loaded with the MA could achieve a significantly better skin regeneration effect than SSAD or MA used alone, providing a simple yet highly effective means to obtain complete, scarless skin regeneration, suggesting favorable potential for clinical translation.

Flour products played a vital role in the global diet structure. With the increasing demand for dietary health and food standardization, the staple food of flour products made from coarse grains due to its unique flavor and rich nutrition has become a trend and is favored by consumers. However, the lack of gluten protein in the raw materials prevented the formation of a stable gluten network structure, leading to the deterioration of the quality of flour products. Ultrasonic treatment, as an innovative food processing technology, generated energy during the action of ultrasonic waves that had a positive impact on the texture, organizational structure, or flavor characteristics of food. That was of great significance for improving food production efficiency, improving food processing quality, and extending food shelf life. This article applied ultrasonic technology to the processing of flour products from the perspective of promoting fermentation and improving production efficiency of flour products. The cavitation effect of ultrasound promoted the formation of gluten network structure, improved the rheology properties of dough and the quality of flour products by promoting protein cross-linking, improving the foaming and emulsifying stability of gluten protein, and promoting the growth and reproduction of yeast. All reviewed studies indicate that ultrasound would be a promising technology for producing high-quality surface products under appropriate conditions.