Insights into the Volatile Flavor Profiles of Two Types of Beef Tallow via Electronic Nose and Gas Chromatography-Ion Mobility Spectrometry Analysis.

In the current study, an electronic nose (E-nose) and gas chromatography-ion mobility spectrometry (GC-IMS) were employed to investigate the volatile flavor compounds (VFCs) of intense flavor beef tallow (L) and ordinary beef tallow (P). The study results indicate that an E-nose combined with an LDA and GC-IMS combined with an OPLS-DA can effectively distinguish between the two types of beef tallow. Compared with ordinary beef tallow, the E-nose sensors of intense flavor beef tallow have stronger response signals to sulfides, terpenes, and nitrogen oxides. A total of 22 compounds contribute to making the flavor of intense flavor beef tallow more typical and richer; in contrast, ethyl acetate was the main aroma-active compound found in the ordinary beef tallow. Sulfur-containing compounds and terpenoids might be the key substances that cause sensory flavor differences between the two types of beef tallow. In conclusion, the results of this study clarify the characteristics and differences of the two types of beef tallow and provide an enhanced understanding of the differences in the flavors of the two types of beef tallow.

Characterization of the distinct immune microenvironments between hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1+ macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.

Optimal concentration of ropivacaine for brachial plexus blocks in adult patients undergoing upper limb surgeries: a systematic review and meta-analysis.

Aim of the Study: Brachial plexus block (BPB) is widely used for patients undergoing upper limb surgeries. Ropivacaine is the most commonly used local anesthetic for BPB. This study aimed to identify the optimal ropivacaine concentration for BPB in adult patients undergoing upper limb surgeries. Materials and Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify randomized controlled trials (RCTs) that compared the effects of different concentrations of ropivacaine for BPB in adult patients undergoing upper limb surgeries. The primary outcomes were the onset time of sensory and motor block. RevMan 5.4 software was used for analysis. The GRADE approach was used to assess evidence quality. Results: Nine studies involving 504 patients were included. Compared to 0.5% ropivacaine, 0.75% ropivacaine shortened the onset time of sensory (WMD, -2.54; 95% CI; -4.84 to -0.24; <0.0001, moderate quality of evidence) and motor blockade (WMD, -2.46; 95% CI, -4.26 to -0.66; p = 0.01; moderate quality of evidence). However, 0.5% and 0.75% ropivacaine provided similar duration time of sensory (WMD, -0.07; 95% CI, -0.88 to 0.74; p = 0.81; high quality of evidence) and motor blockade (WMD, -0.24; 95% CI, -1.12 to 0.65; p = 0.55; high quality of evidence), as well as time to first request for oral analgesia (WMD, -1.57; 95% CI, -3.14 to 0.01; p = 0.5; moderate quality of evidence). Conclusion: Moderate-quality evidence suggested that, in terms of the onset time of sensory and motor blockade, 0.75% ropivacaine is a preferred concentration for BPB in upper limb surgeries. Systematic Review Registration: identifier CRD42023392145.

NIR-dye bridged human serum albumin reassemblies for effective photothermal therapy of tumor.

Human serum albumin (HSA) based drug delivery platforms that feature desirable biocompatibility and pharmacokinetic property are rapidly developed for tumor-targeted drug delivery. Even though various HSA-based platforms have been established, it is still of great significance to develop more efficient preparation technology to broaden the therapeutic applications of HSA-based nano-carriers. Here we report a bridging strategy that unfastens HSA to polypeptide chains and subsequently crosslinks these chains by a bridge-like molecule (BPY-Mal2) to afford the HSA reassemblies formulation (BPY@HSA) with enhanced loading capacity, endowing the BPY@HSA with uniformed size, high photothermal efficacy, and favorable therapeutic features. Both in vitro and in vivo studies demonstrate that the BPY@HSA presents higher delivery efficacy and more prominent photothermal therapeutic performance than that of the conventionally prepared formulation. The feasibility in preparation, stability, high photothermal conversion efficacy, and biocompatibility of BPY@HSA may facilitate it as an efficient photothermal agents (PTAs) for tumor photothermal therapy (PTT). This work provides a facile strategy to enhance the loading capacity of HSA-based crosslinking platforms in order to improve delivery efficacy and therapeutic effect.

Nanocompartment-confined polymerization in living systems.

Polymerization in living systems has become an effective strategy to regulate cell functions and behavior. However, the requirement of high concentrations of monomers, the existence of complicated intracorporal interferences, and the demand for extra external stimulations hinder their further biological applications. Herein, a nanocompartment-confined strategy that provides a confined and secluded environment for monomer enrichment and isolation is developed to achieve high polymerization efficiency, reduce the interference from external environment, and realize broad-spectrum polymerizations in living systems. For exogenous photopolymerization, the light-mediated free-radical polymerization of sodium 4-styrenesulfonate induces a 2.7-fold increase in the reaction rate with the protection of a confined environment. For endogenous hydrogen peroxide-responsive polymerization, p­aminodiphenylamine hydrochloride embedded in a nanocompartment not only performs a 6.4-fold higher reaction rate than that of free monomers, but also activates an effective second near-infrared photoacoustic imaging-guided photothermal immunotherapy at tumor sites. This nanocompartment-confined strategy breaks the shackles of conventional polymerization, providing a universal platform for in vivo synthesis of polymers with diverse structures and functions.

Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging.

Organic small-molecule contrast agents have attracted considerable attention in the field of multispectral optoacoustic imaging, but their weak optoacoustic performance resulted from relatively low extinction coefficient and poor water solubility restrains their widespread applications. Herein, we address these limitations by constructing supramolecular assemblies based on cucurbit[8]uril (CB[8]). Two dixanthene-based chromophores (DXP and DXBTZ) are synthesized as the model guest compounds, and then included in CB[8] to prepare host-guest complexes. The obtained DXP-CB[8] and DXBTZ-CB[8] display red-shifted and increased absorption as well as decreased fluorescence, thereby leading to a substantial enhancement in optoacoustic performance. Biological application potential of DXBTZ-CB[8] is investigated after co-assembly with chondroitin sulfate A (CSA). Benefiting from the excellent optoacoustic property of DXBTZ-CB[8] and the CD44-targeting feature of CSA, the formulated DXBTZ-CB[8]/CSA can effectively detect and diagnose subcutaneous tumors, orthotopic bladder tumors, lymphatic metastasis of tumors and ischemia/reperfusion-induced acute kidney injury in mouse models with multispectral optoacoustic imaging.

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

Oral Intake of Chicken Bone Collagen Peptides Anti-Skin Aging in Mice by Regulating Collagen Degradation and Synthesis, Inhibiting Inflammation and Activating Lysosomes.

The effect of diet on skin aging has become an interesting research topic. Previous studies have mostly focused on the beneficial effects of collagen peptides derived from marine organisms on the aging skin when administered orally, while the beneficial effects of collagen peptides derived from poultry on aging skin have been rarely reported. In this study, collagen peptides were prepared from chicken bone by enzymatic hydrolysis, and the effect and mechanism of action of orally administered collagen peptides on alleviating skin aging induced by UV combined with D-galactose were investigated. The results showed that the chicken bone collagen had typical characteristics of collagen, and the chicken bone collagen peptides (CPs) were mainly small molecular peptides with a molecular weight of <3000 Da. In vivo experiments showed that CPs had a significant relieving effect on aging skin, indicated by the changes in the compostion and structure of the aging skin, improvement of skin antioxidant level, and inhibition of inflammation; the relieving effect was positively correlated with the dose of CPs. Further investigation showed that CPs first reduce the level of skin oxidation, inhibit the expression of the key transcription factor AP-1 (c-Jun and c-Fos), then activate the TGF-ß/Smad signaling pathway to promote collagen synthesis, inhibit the expression of MMP-1/3 to inhibit collagen degradation, and inhibit skin inflammation to alleviate skin aging in mice. Moreover, the skin transcriptome found that lysosomes activated after oral administration of CPs may be an important pathway for CPs in anti-skin aging, and is worthy of further research. These results suggested that CPs might be used as a functional anti-aging nutritional component.

Animal by-products collagen and derived peptide, as important components of innovative sustainable food systems-a comprehensive review.

In 2020, the world's food crisis and health industry ushered into a real outbreak. On one side, there were natural disasters such as the novel coronavirus (2019-nCoV), desert locusts, floods, and droughts exacerbating the world food crisis, while on the other side, the social development and changes in lifestyles prompted the health industry to gradually shift from a traditional medical model to a new pattern of prevention, treatment, and nourishment. Therefore, this article reviews animal by-products collagen and derived peptide, as important components of innovative sustainable food systems. The review also considered the preparation, identification, and characterization of animal by-product collagen and collagen peptides as well as their impacts on the food system (including food processing, packaging, preservation, and functional foods). Finally, the application and research progress of animal by-product collagen and peptide in the food system along with the future development trend were discussed. This knowledge would be of great significance for a comprehensive understanding of animal by-product collagen and collagen peptides and would encourage the use of collagen in food processing, preservation, and functional foods.

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging.

Developing high-quality NIR-II fluorophores (emission in 1000-1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

Missing-Linker-Assisted Artesunate Delivery by Metal-Organic Frameworks for Synergistic Cancer Treatment.

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of an ATS nanomedicine through the self-assembly with Mn[Co(CN)6 ]2/3 □1/3 metal-organic frameworks (MOFs) that have hidden missing linkers. The defects in MOFs originating from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co-loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3- , Mn2+ acts as an efficient catalyst to promote the bicarbonate-activated H2 O2 system which oxidizes ATS to generate reactive oxygen species and induce oxidative death to cancer cells. The released [CoIII (CN)6 ] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect-engineered MOFs with hidden missing linkers hold great promise in advancing the practical use of ATS as an antitumor medicine.

Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.

Metal-Organic Framework Derived Multicomponent Nanoagent as a Reactive Oxygen Species Amplifier for Enhanced Photodynamic Therapy.

Intracellular antioxidants such as glutathione (GSH) play a critical role in protecting malignant tumor cells from apoptosis induced by reactive oxygen species (ROS) and in mechanisms of multidrug and radiation resistance. Herein, we rationally design two multicomponent self-assembled photodynamic therapy (PDT) nanoagents, that is, Glup-MFi-c and Glud-MFo-c, which consist of respective GSH-passivation and GSH-depletion linkers in metal-organic frameworks encapsulated with photosensitizers for a deeply comprehensive understanding of GSH-based tumor PDT. Multicomponent coordination, π-π stacking, and electrostatic interactions among metal ions, photosensitizers, and bridging linkers under the protection of a biocompatible polymer generate homogeneous nanoparticles with satisfied size, good colloid stability, and ultrahigh loading capacity. Compared to the GSH-passivated Glup-MFi-c, the GSH-depleted Glud-MFo-c shows pH-responsive release of photosensitizer and [FeIII(CN)6] linker in tumor cells to efficiently deplete intracellular GSH, thus amplifying the cell-killing efficiency of ROS and suppressing the tumor growth in vivo. This study demonstrates that Glud-MFo-c acts as a ROS amplifier, providing a useful strategy to deeply understand the role of GSH in combating cancer.

An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition.

Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcome. Methods: Tumor hypoxia can cleave the azo linker and release a NIR fluorophore (NR-NH2) and release the active drug as well. NR-NH2 shows a strong absorption band at around 680 nm and a strong fluorescence band at 710 nm, allowing for both multispectral optoacoustic tomography imaging (MSOT) and fluorescent imaging of tumor hypoxia in a tumor-bearing mouse model. Results: Liposome encapsulated with the activatable chromophore (NR-azo) for detecting/imaging tumor hypoxia and for tumor inhibition was demonstrated. For this chromophore, a xanthene-based NIR fluorophore acts as the optoacoustic and fluorescent reporter, an azo linker serves as the hypoxia-responsive moiety and a nitrogen mustard as the therapeutic drug. NR-azo shows an absorption at around 575 nm but exhibits negligible fluorescence due to the existence of the strong electron-withdrawing azo linker. Conclusion: We demonstrated an optoacoustic and fluorescent system for not only imaging tumor hypoxia in vivo but also achieving tumor inhibition.

Acute oral toxicity test and assessment of combined toxicity of cadmium and aflatoxin B1 in kunming mice.

Cadmium and aflatoxin B1 (AFB1) are both common and widespread pollutants in food and feed. There are several reports on toxicity induced by Cadmium or AFB1 alone, but few address the toxicity caused by co-exposure to the two substances. In this study, 42 female and 42 male Kunming (KM) mice were divided into seven groups to test the acute oral toxicity of CdCl2 and AFB1, using Karber's method. The combined toxicity was assessed using the Keplinger evaluation system. Acute toxicity symptoms, deaths, and body and organ weights were evaluated, and hematological, blood biochemical, and histopathological analyses were conducted. The results revealed the following median lethal doses (LD50): LD50(Female KM mice) = 62.56 mg/kg; LD50(Male KM mice) = 48.79 mg/kg; LD50(KM mice)=55.27 mg/kg. The combined toxicity of AFB1 and CdCl2 showed an additive effect in mice, and an increase in the mixed dose of AFB1 and CdCl2 resulted in greater toxicity. These results demonstrated that the combined toxicity of AFB1 and CdCl2 was greater than the toxicities of the individual components in mice; thus, this may cause particular challenges when addressing these hazards in food and feed and the associated risk to human and animal health.

A Turn-On Optoacoustic Probe for Imaging Metformin-Induced Upregulation of Hepatic Hydrogen Sulfide and Subsequent Liver Injury.

Metformin is currently the most prescribed oral agent for diabetes treatment; however the overdose or long-term use may cause some severe side effects such as liver injury. Researches indicate that metformin-induced liver injury is closely related to upregulation of hepatic H2S. Hence, monitoring hepatic H2S generation induced by metformin could be an effective approach for evaluating hepatoxicity of the drug. Methods: We present a novel turn-on and dual-mode probe for detecting and imaging metformin-induced liver injury by specifically tracking the upregulation of hepatic H2S with fluorescent and optoacoustic methods. After reaction with H2S, the strong electron-withdrawing group dinitrophenyl ether (which acts as both the recognition moiety and the fluorescence quencher) was cleaved and replaced by an electron-donating group hydroxyl. This correspondingly leads to the changes of the probe's electronic state and absorption red-shifting as well as the subsequent turn-on fluorescent and optoacoustic signals. Results: The probe was applied to the colon tumor-bearing mice model and the metformin-induced liver injury mice model to achieve tumor imaging and liver injury assessment. The biosafety of the probe was verified by histological analysis (hematoxylin and eosin staining) and serum biochemical assays. Conclusion: The probe responds quickly to H2S in tumors and the liver, and MSOT imaging with the probe offers cross-secitonal and 3D spatial information of liver injury. This study may provide an effective approach for accessing medication side effects by tracking drug-metabolism-related products.

Activatable probes for diagnosing and positioning liver injury and metastatic tumors by multispectral optoacoustic tomography.

Optoacoustic tomography (photoacoustic tomography) is an emerging imaging technology displaying great potential for medical diagnosis and preclinical research. Rationally designing activatable optoacoustic probes capable of diagnosing diseases and locating their foci can bring into full play the role of optoacoustic tomography (OAT) as a promising noninvasive imaging modality. Here we report two xanthene-based optoacoustic probes (C1X-OR1 and C2X-OR2) for temporospatial imaging of hepatic alkaline phosphatase (or ß-galactosidase) for evaluating and locating drug-induced liver injury (or metastatic tumor). The probes rapidly respond to the disease-specific biomarkers by displaying red-shifted NIR absorption bands and generate prominent optoacoustic signals. Using multispectral optoacoustic tomography (MSOT), we can precisely localize the focus of drug-induced liver injury in mice using C1X-OR1, and the metastatic tumors using C2X-OR2. This work suggests that the activatable optoacoustic chromophores may potentially be applied for diagnosing and localizing disease foci, especially smaller and deeper ones.

A turn-on fluorescence probe based on aggregation-induced emission for leucine aminopeptidase in living cells and tumor tissue.

Abnormally-expressed leucine aminopeptidase (LAP) is associated with diverse physiological and pathological disorders; hence developing a highly selective and sensitive detection system for LAP is of great significance. Herein, a fluorescent light-up system with aggregation-induced emission (AIE) characteristic, (DPA-TPE-Leu) has been developed for detecting LAP, in which the recognition unit l-leucine amide group also acts as the hydrophilic moiety. Upon LAP-triggered enzymatic reaction, l-leucine amide moiety is cleaved from the probe molecule, resulting in the formation and aggregation of the hydrophobic reaction product (DPE-TPE-OH) with AIE effect and thus giving out the turn-on green fluorescence. The system features excellent photostability, large Stokes shift (194 nm), good water solubility, high sensitivity with the detection limit of 0.16 U L-1, favorable specificity and low cytotoxicity. It has been effectively utilized in fluorescent imaging of endogenous LAP in living cells, and also successfully applied for fluorescent imaging of HepG2 xenograft tumor. Such a fluorescent assay could provide a convenient and sensitive method for detecting LAP activity and might aid in the auxiliary diagnosis of hepatocellular carcinoma and related pathological analysis in biopsy.

AIE fluorophore with enhanced cellular uptake for tracking esterase-activated release of taurine and ROS scavenging.

Fluorophores with aggregation-induced emission (AIE) characteristics are attractive and versatile tools for both chemical sensing and biological imaging. Herein, we designed and synthesized a fluorescent light-up system CTPE-Tau with enhanced cellular uptake ability. The system possesses several advantages, such as a large Stokes shift, low cytotoxicity, and good photostability. Also, it has been successfully utilized to track esterase-activated release of taurine and to scavenge intracellular ROS, and shows great potential for trackable visualized therapy.

A ratiometric fluorescent probe for aluminum ions based-on monomer/excimer conversion and its applications to real samples.

Excessive amount of aluminum is detrimental to growing plants or animals and people are likely to suffer from various diseases upon long-term exposure to aluminum ions. Therefore, sensitive and selective detection of trace amounts of Al(3+) in real samples is of great importance. Herein, a ratiometric fluorescent probe for detecting aluminum ions based on pyrene-1-butyric acid (Py-L-COOH) was developed, which function via monomer/excimer conversion. In the presence of Al(3+), the original monomer-state Py-L-COOH molecules coordinate with Al(3+) and form excimer, thus changing the emission wavelength from 350-400nm to 450-500nm and achieving the ratiometric detection for Al(3+). The probe responds to Al(3+) quickly and can be operable in aqueous media with a very low detection limit of 0.29µM. This system is capable of detecting Al(3+) in real samples and shows high selectivity. Furthermore, the probe exhibits low cytotoxicity and can be used in fluorescence imaging in Hela cell lines. The approach may provide an effective simple probe for aluminum ions determination with application to real samples, as well as offering insights for designing facile ratiometric fluorescent sensors.