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Abstract Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring. Graphical abstract

The utility of circular RNAs (circRNAs) as emerging biomarkers and regulatory factors in medical diagnostics and therapeutics is hampered by the challenges associated with their sensitive detection and precise modulation. Herein, a high‐performance cooperative DNA nanodevice (HCDN) based on DNA tetrahedron‐confined catalytic DNA assembly reaction (DT‐CDA) that enables both imaging and regulation of circRNAs is developed. Activation of the DT‐CDA is contingent upon the presence of the target circRNA, which, together with a replicative fuel probe, catalyzes the sequential opening of additional DT‐CDAs. This cooperative exponential signal amplification with negligible background interference allows HCDN to effectively detect minute quantities of circRNAs. Employing circSATB2 as a model, the HCDN demonstrates substantial downregulation of Cyclin D1 (CCND1) mRNA and protein levels in cellular and in vivo models, thereby inhibiting tumor growth. The innovative design of HCDN sets the stage for a powerful methodology conducive to enhanced clinical diagnostics and biomolecule manipulation, thereby advancing the capabilities and applications of DNA nanotechnology.

Abstract Regulation of excessive inflammation and impaired cell proliferation is crucial for healing diabetic wounds. Although plant‐to‐mammalian regulation offers effective approaches for chronic wound management, the development of a potent plant‐based therapeutic presents challenges. This study aims to validate the efficacy of turmeric‐derived nanoparticles (TDNPs) loaded with natural bioactive compounds. TDNPs can alleviate oxidative stress, promote fibroblast proliferation and migration, and reprogram macrophage polarization. Restoration of the fibroblast–macrophage communication network by TDNPs stimulates cellular regeneration, in turn enhancing diabetic wound healing. To address diabetic wound management, TDNPs are loaded in an ultralight‐weight, high swelling ratio, breathable aerogel (AG) constructed with cellulose nanofibers and sodium alginate backbones to obtain TDNPs@AG (TAG). TAG features wound shape‐customized accessibility, water‐adaptable tissue adhesiveness, and capacity for sustained release of TDNPs, exhibiting outstanding performance in facilitating in vivo diabetic wound healing. This study highlights the potential of TDNPs in regenerative medicine and their applicability as a promising solution for wound healing in clinical settings.

Abstract Fluorescent dyes that emit in the second near‐infrared (NIR‐II, 1000–3000 nm) region have provided significant advances toward real‐time and high‐resolution imaging of vessel and lymphatic system. However, in vivo NIR‐II tracking of the fate of labeled cells still remains challenging. Here, we develop a shielding unit–donor–acceptor–donor–shielding unit (S‐D‐A‐D‐S) NIR‐II fluorophore (FE‐4ZW) with zwitterionic terminal groups for high‐efficiency cell labeling without using cell‐penetrating peptides, which provides for enhanced non‐invasive in vivo determination of the location of cell migration. The tethering terminal sulfoammonium inner salts are featured with its high affinity for cell membranes, thereby enabling the stable labeling even for fixed cells. The fate of transplanted stem cell and the tumor cell migration along lymphatic system in brain or periphery tissues are clearly monitored by the cell‐internalized FE‐4ZW. We also confirmed that a clinically used surfactant, D‐α‐tocopheryl polyethylene glycol‐1000 succinate, can reduce the liver and spleen uptake of FE‐4ZW. The fluorophore design strategy and cell‐labeling technology reported here open a new realm in the visualization of cell migration and insight into the relocation process, thereby ultimately providing an opportunity to investigate in greater detail of the underlying mechanisms of stem cell therapy and tumor metastasis.

Abstract In recent years, the important role of gut microbiota in promoting animal health and regulating immune function in livestock and poultry has been widely reported. The issue of animal health problems causes significant economic losses each year. Probiotics and postbiotics have been widely developed as additives due to their beneficial effects in balancing host gut microbiota, enhancing intestinal epithelial barrier, regulating immunity, and whole‐body metabolism. Probiotics and postbiotics are composed of complex ingredients, with different components and compositions having different effects, requiring classification for discussing their mechanisms of action. Probiotics and postbiotics have considerable prospects in preventing various diseases in the livestock industry and animal feed and medical applications. This review highlights the application value of probiotics and postbiotics as potential probiotic products, emphasizing their concept, mechanism of action, and application, to improve the productivity of livestock and poultry.

Weaned stress may damage the tissue development, barrier function, and balance of microbiota of gut, resulting in the diarrhea and reduced growth performance of piglets. Probiotics with excellent characteristics can enhance the resistance of piglets to weaned stress. Under a poor sanitary condition, the Limosilactobacillus reuteri (L. reuteri) SLZX19-12 was supplemented to check its effects for piglets. Results showed that supplementation of L. reuteri significantly decreased the diarrhea incident, improved the growth performance, and enhanced the barrier integrity of gut. In ileum, L. reuteri decreased inflammation by NFκB p65 pathway, increased propionate, TCDCA, and THDCA contents, and regulated microbiota. In colon, L. reuteri decreased the inflammation by NFκB p65 pathway, reduced DCA content, and regulated microbiota. Therefore, the supplementation of L. reuteri may alleviate weaned stress by improving immune function and regulating the gut microbiota in piglets.

Highlights Two series of terpolymers with improved photostability were realized by the introduction of appropriate ratio of antioxidant butylated hydroxytoluene unit containing side chains. All-polymer solar cells and organic photodetectors (OPDs) with these terpolymers as both donors and acceptors have been prepared with simultaneously improved efficiency and stability. A feasible approach to develop terpolymers with antioxidant efficacy for improving the lifetime of organic solar cells and OPDs is proposed.

Abstract A donor–acceptor (D-A) conjugated polymer PBTFO-T-1 consisting of 2,1,3-benzothiadiazole (BT) as A unit and thiophene (T) as D unit was facilely obtained by a straightforward three-step reaction. The BT unit is attached with a fluorine atom and an alkoxy chain to simultaneously endow the polymer with a deep HOMO energy level and desirable solubility. The alkoxyl chain orientation on the BT unit has been regulated and the polymer PBTFO-T-2 with regio-regularly oriented side chains was also developed to investigate the impact of the alkoxyl chain orientation on their optoelectronic properties. The PBTFO-T-1:Y6-BO polymer solar cells (PSCs) were processed with a non-halogenated solvent and achieved an optimized power conversion efficiency of 14.16%, significantly higher than 9.39% of the PBTFO-T-2:Y6-BO counterpart. It has been demonstrated that the PBTFO-T-1:Y6-BO film exhibits higher and more balanced charge transportation and superior film morphology, resulting in higher exciton generation and dissociation, less recombination and eventually the higher short-circuit current density (J sc) and fill factor. This study provides a possible strategy to develop polymer donors with low cost for future commercial applications of PSCs and gives some insights into regulating optoelectronic properties of polymer donors via rationally modifying their side chain orientation.

The second near-infrared (NIR-II, 1,000 to 1,700 nm) molecular fluorophores containing donor–acceptor–donor conjugated backbone have attracted substantial attention due to their outstanding advantages, such as stable emission and facilely tuned photophysical properties. However, it is still challenging for them to simultaneously achieve high brightness and red-shifted absorption and emission. Herein, furan is adopted as the D unit to construct NIR-II fluorophores, demonstrating red shift of absorption, enhanced absorption coefficient, and fluorescent quantum yield when compared with the generally used thiophene counterparts. The high brightness and desirable pharmacokinetics of the optimized fluorophore, IR-FFCHP, endows improved performance for angiography and tumor-targeting imaging. Furthermore, dual-NIR-II imaging of tumor and sentinel lymph nodes (LNs) has been achieved with IR-FFCHP and PbS/CdS quantum dots, enabling the in vivo imaging navigated LN surgery in tumor-bearing mice. This work demonstrates the potential of furan for constructing bright NIR-II fluorophores for biological imaging.

Linoleic acid (LA), a potentially algae-inhibiting chemical released by macroalgae, has been shown to hinder the growth of numerous bloom-forming species. The allelopathic effects of LA (varying from 100 μg/L to 900 μg/L) on harmful microalgae K. mikimotoi were examined using population growth dynamics and physiological levels of K. mikimotoi. LA (>500 μg/L) strongly inhibited algal growth with most cells halted at the S and G2 phases and an evident drop in photosynthetic pigments (chlorophyll a (chl a), chlorophyll c (chl c) and carotenoids). Furthermore, chlorophyll fluorescence parameters such as Fv/Fm, PI, ETo/RC showed a declining trend whereas ABS/RC, DIo/RC, TRo/RC showed an increasing trend with increasing LA exposure concentrations. The level of intracellular reactive oxygen species (ROS) was considerably higher, indicating that LA promoted oxidative stress in K. mikimotoi. Excessive ROS promoted apoptosis in K. mikimotoi, which was noted by increased activity of caspase-3, caspase-9, and flow cytometry (FCM) data. Furthermore, N-acetylcysteine (NAC) and N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) lowered the apoptotic rates of the LA-treated algal cells, indicating that the aforementioned inhibitors delayed K. mikimotoi apoptosis under LA treatment. To summarize, cell cycle arrest of K. mikimotoi is less sensitive to ROS, but the overproduction of ROS generated by LA activated caspase-3 and caspase-9, which further promoted the apoptosis of K. mikimotoi. This research showed that LA might have great potential and application prospects in controlling the outbreak of harmful algae.

Artificial intelligence (AI) is fundamentally transforming smart buildings by increasing energy efficiency and operational productivity, improving life experience, and providing better healthcare services. Sudden Infant Death Syndrome (SIDS) is an unexpected and unexplained death of infants under one year old. Previous research reports that sleeping on the back can significantly reduce the risk of SIDS. Existing sensor-based wearable or touchable monitors have serious drawbacks such as inconvenience and false alarm, so they are not attractive in monitoring infant sleeping postures. Several recent studies use a camera, portable electronics, and AI algorithm to monitor the sleep postures of infants. However, there are two major bottlenecks that prevent AI from detecting potential baby sleeping hazards in smart buildings. In order to overcome these bottlenecks, in this work, we create a complete dataset containing 10,240 day and night vision samples, and use post-training weight quantization to solve the huge memory demand problem. Experimental results verify the effectiveness and benefits of our proposed idea. Compared with the state-of-the-art AI algorithms in the literature, the proposed method reduces memory footprint by at least 89%, while achieving a similar high detection accuracy of about 90%. Our proposed AI algorithm only requires 6.4 MB of memory space, while other existing AI algorithms for sleep posture detection require 58.2 MB to 275 MB of memory space. This comparison shows that the memory is reduced by at least 9 times without sacrificing the detection accuracy. Therefore, our proposed memory-efficient AI algorithm has great potential to be deployed and to run on edge devices, such as micro-controllers and Raspberry Pi, which have low memory footprint, limited power budget, and constrained computing resources.

Based on the characteristic of low diarrhea in native Chinese breeds, we introduce the enterotype model for piglets, which is a new perspective to decipher the colonization and the transition of the gut microbiota among various pig breeds. After eliminating environmental influences represented by diet, the microbiota, mainly shaped by host genetics, is focused. Three representative enterotype clusters were identified, which were represented by Bacteroides, Streptococcus, and Lactobacillus. Chinese native breeds were distributed in enterotype 1 (E1) and E3, which collectively drove the diversification and functionality of the microbial community of various Chinese pig breeds. Next, the Lactobacillus reuteri (L. reuteri), which is the representative strain of E3, was specifically isolated in all three enterotypes. The excellent stress-resistance of L. reuteri-E3 not only highlighted the stronger disease resistance of Chinese breeds but also had a great potential to intervene in weaned piglet diseases. Enterotype classification based on host genetics is much more deterministic and predictable, clarifying the driver of the host-microbiome dynamics and constructing the picture of the micro-coevolution of human host genetics with the gut microbiome.

Molecular fluorophores emitting in the second near-infrared (NIR-II) window with good renal excretion ability are favorable for in vivo bio-imaging and clinical applications. So far, renally excretable fluorophores are still less studied. Understanding the influences of molecular structure on optical properties and renal excretion abilities are vital for fluorophore optimization. Herein, a series of shielding unit-donor-acceptor-donor-shielding unit (S-D-A-D-S) NIR-II molecular fluorophores are designed and synthesized with dialkoxy chains substituted benzene as the S unit. The anchoring positions of dialkoxy chains on benzene are tuned as meso-2,6, para-2,5, or ortho-3,4 to afford three fluorophores: BGM6P, BGP6P and BGO6P, respectively. Experimental and calculation results reveal that alkoxy side chains anchored closer to the conjugated backbone can provide better protection from water molecules and PEG chains, affording higher fluorescence quantum yield (QY) in aqueous solutions. Further, these side chains can enable good encapsulation of backbone, resulting in decreased binding with albumin and improved renal excretion. Thus, fluorophore BGM6P with meso-2,6-dialkoxy chains exhibits the highest quantum yield and fastest renal excretion. This work emphasizes the important roles of side chain patterns on optimizing NIR-II fluorophores with high brightness and renal excretion ability.

The utilization of extracellular vesicles (EVs) in clinical theranostics has rapidly advanced in the past decade. In November 2018, the International Society for Extracellular Vesicles (ISEV) held a workshop on “EVs in Clinical Theranostic”. Here, we report the conclusions of roundtable discussions on the current advancement in the analysis technologies and we provide some guidelines to researchers in the field to consider the use of EVs in clinical application. The main challenges and the requirements for EV separation and characterization strategies, quality control and clinical investigation were discussed to promote the application of EVs in future clinical studies.

Spirulina platensis is a blue-green algae with potential anti-obesity effects. In this study, the anti-obesity effects of whole Spirulina platensis (WSP), Spirulina platensis protein (SPP) and Spirulina platensis protein hydrolysate (SPPH) were compared in high-fat diet fed mice, and the potential acting mechanism of SPPH was also investigated. Totally, SPPH exhibited good anti-obesity effects (reducing 39.8%±9.7% of body weight), lowering 23.8%±1.6% of serum glucose, decreasing 20.8%±1.4% of total cholesterol, while positive drug Simvastatin had the corresponding values: 8.3%±4.6%, 24.8%±1.9% and -2.1%±0.2%, respectively. Subsequently, PCR array was used to conduct gene expression analysis in brain and liver tissues of SPPH-treated mice, which displayed distinctly different expression pattern. The most markedly changed genes included: Acadm (-34.7 fold), Gcg (2.5 fold), Adra2b (2 fold) and Ghsr (2 fold) in brain; Retn (39 fold), Fabp4 (15.5 fold), Ppard (6 fold) and Slc27a1 (5.4 fold) in liver. Further network analysis demonstrated that the significantly expressed genes in brain and liver tissues were mapped into an interacting network, suggesting a modulatory effect on brain-liver axis, major pathways were involved in the axis: PPAR, adipocytokine, AMPK, non-alcoholic fatty liver disease and MAPK. This study showed that Spirulina platensis protein hydrolysate possessed anti-obesity effect in mice.

The toxic effects of the typically noxious bloom-forming dinoflagellate Karenia mikimotoi were studied using the allelopathic experimental system under controlled laboratory conditions. The potency of intact cell suspensions with whole cells, cell-free culture filtrate in different growth phases, and lysed cells with ultrasonication were compared, and the growth and reproduction of the marine rotifer Brachionus plicatilis were used as endpoints to evaluate toxic differences. The intact cell suspension resulted the most significant growth inhibition, including lethality, on the growth of B. plicatilis (p < 0.05). Lysed culture medium treated with ultrasonication and the cell-free culture filtrates at either the exponential or stationary phase exhibited limited negative impacts compared to the control according to changes in the population growth rate (r) and survival rate (p > 0.05). Reproduction presented a similar tendency to change, and the number of eggs produced per individual, as well as spawning period decreased in the whole cell and lysed cell suspensions. The key parameters in the lift table include the net reproductive rate (R0) and the intrinsic rate of increase (rm), which were more sensitive to treatment and were significantly suppressed compared to that of the control. The addition of the ROS inhibitor N-acetylcysteine (NAC) could not change the growth or reproduction patterns. Moreover, substantial hemolytic toxicity was found in the treatment of the intact cell suspension (p < 0.05), while limited toxicity was found in other treatments compared to that of the control. K. mikimotoi was speculated to secrete allelopathic substances onto the cell surface, and direct cell contact was necessary for allelopathic toxicity in B. plicatilis. Reactive oxygen species (ROS)-independent hemolytic toxicity was assumed to be the explanation for what was observed.

Background: There is a big difference in the expression of miRNAs of plasma exosomes of patients with HBV infection. This study aims to analyze four molecular markers of peripheral blood plasma exosomes to evaluate their potential diagnostic values in HBV infection. Methods: A total of 55 cases of patients with chronic hepatitis B were in Experimental Group 1; 49 cases of hepatitis B carriers were in Experimental Group 2, and 46 cases were in the healthy control group. The total RNA of the plasma exosome was used to analyze the specificity and sensitivity and draw ROC curves. Results: There was a significant difference in the expression of miRNA-1246, miRNA-150-5p, miRNA-5787, and miRNA-8069 down-regulated by plasma exosomes in Experimental Group 1 and Group 2 and Control Group, with a p value of less than 0.05. Conclusions: The molecular markers down-regulated were miRNA-1246, miRNA-150-5p, miRNA-5787, and miRNA-8069. The four miRNAs were initially identified as new markers of miRNAs of peripheral blood plasma exosomes after HBV infection. It is better to use multiple markers for combined diagnosis. [ABSTRACT FROM AUTHOR]

A simple, clean method of steam etching carbon nanotubes is reported for the synthesis of graphene nanoribbons. The chemical mechanism of carbon nanotube unzipping is also discussed. As an anode catalyst, as-prepared graphene nanoribbons combined with Pt exhibit quite a high catalytic activity for ethanol electro-oxidation in fuel cells. [ABSTRACT FROM AUTHOR]

In observational studies, it is important to evaluate not only the total effect but also the direct and indirect effects of a treatment variable on a response variable. In terms of local structural learning of causal networks, we try to find all possible pairs of total and direct causal effects, which can further be used to calculate indirect causal effects. An intuitive global learning approach is first to find an essential graph over all variables representing all Markov equivalent causal networks, and then enumerate all equivalent networks and estimate a pair of the total and direct effects for each of them. However, it could be inefficient to learn an essential graph and enumerate equivalent networks when the true causal graph is large. In this paper, we propose a local learning approach instead. In the local learning approach, we first learn locally a chain component containing the treatment. Then, if necessary, we learn locally a chain component containing the response. Next, we locally enumerate all possible pairs of the treatment's parents and the response's parents. Finally based on these pairs, we find all possible pairs of total and direct effects of the treatment on the response. [ABSTRACT FROM AUTHOR]