Long-term administration of royal jelly regulates age-related disorders and improves gut function in naturally aging mice.

A natural aging mouse model can exhibit physiological characteristics that closely resemble those of human aging. Through long-term observation, it reflects the occurrence and development of the aging process more accurately. Although numerous beneficial effects of royal jelly (RJ) have been extensively demonstrated in multiple experimental models, the effects of RJ on naturally aging mice have not yet been investigated. In this study, middle-aged male C57BL/6J mice were given RJ for 9 consecutive months to investigate its impact on the intestinal barrier function, gut microbiota, short-chain fatty acids (SCFAs) content and possible mechanisms. The results confirmed that RJ modulated serum lipids by reducing the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Additionally, it protected the liver by increasing antioxidant enzyme levels while decreasing inflammatory cytokines TNF-α (by 51.97%), IL-6 (by 29.73%), and IL-1ß (by 43.89%). Furthermore, RJ inhibited the expression of cell cycle-dependent kinase inhibitors including p16, p21, and p53. Importantly, RJ ameliorated gut dysfunctions by inhibiting reduction of tight junction proteins and reducing inflammatory cytokines content in the colon. We also observed an alteration in gut microbiota characterized by an elevated ratio of Firmicutes to Bacteroides (F/B) along with increased abundance of beneficial bacteria, i.e., Lachnospiraceae NK4A136 and Akkermansia. Correlation analysis revealed positive associations between most bacterial genera and SCFAs production. Functional profiling of gut microbiota composition indicated that RJ intervention regulated amino acid metabolism, glycan biosynthesis, and cofactor/vitamin metabolism. Overall, our findings provide an effective dietary intervention strategy for modulating age-associated frailty through the modulation of the gut microbiota.

Rapid screening of infertility-associated gynecological conditions via ambient glow discharge mass spectrometry utilizing urine metabolic fingerprints.

Infertility presents a widespread challenge for many families worldwide, often arising from various gynecological diseases (GDs) that hinder successful pregnancies. Current diagnostic methods for GDs have disadvantages such as low efficiency, high cost, misdiagnose, invasive injury and etc. This paper introduces a rapid, non-invasive, efficient, and straightforward analytical method that utilizes desorption, separation, and ionization mass spectrometry (DSI-MS) platform in conjunction with machine learning (ML) to detect urine metabolite fingerprints in patients with different GDs. We analyzed 257 samples from patients diagnosed with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), endometriosis (EMS), recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and 87 samples from healthy control (HC) individuals. We identified metabolite differences and dysregulated pathways through dimensionality reduction methods, with the result of the discovery of 7 potential biomarkers for GDs diagnosis. The ML method effectively distinguished subtle differences in urine metabolite fingerprints. We anticipate that this innovative approach will offer a patient-friendly, rapid screening, and differentiation method for infertility-related GDs patients.

Rapid analysis and authentication of Chinese propolis using nanoelectrospray ionization mass spectrometry combined with machine learning.

In this study, we established a simple, rapid, and high-throughput method for the analysis and classification of propolis samples. We utilized nanoESI-MS to analyze 37 samples of propolis from China for the first time, obtaining characteristic fingerprint spectra in negative ion mode, which were then integrated with multivariate analysis to explore variations between water extract of propolis (WEP) and ethanol extract of propolis (EEP). Furthermore, we categorized propolis samples based on different climate zones and colors, screening 10 differential metabolites among propolis from various climate zones, and 11 differential metabolites among propolis samples of different color. By employing machine learning models, we achieved high-precision discrimination and prediction between samples from different climate zones and colors, achieving predictive accuracies of 95.6% and 85.6%, respectively. These results highlight the significant potential of the nanoESI-MS coupled with machine learning methodology for precise classification within the realm of food products.

Rapid characterization of Maillard reaction products in heat-treated honey by nanoelectrospray ionization mass spectrometry.

Amadori rearrangement products (ARPs) and α-dicarbonyl compounds (α-DCs) are critical intermediates in the Maillard chemistry. The screening of artificially heated honey (AH) is currently based on chromatography-mass spectrometry, which is commonly accompanied with the longer pretreatment and detection time. Here, low-abundance ARPs were detected directly in high-sugar environment by nanoelectrospray ionization mass spectrometry (nanoESI-MS) coupled with borosilicate glass capillaries (O-tips). When O-tips were replaced by borosilicate theta capillaries (θ-tips), the microdroplets allowed the derivatization of α-DCs to be accomplished on the millisecond timescale, rather than hours in conventional protocols. The results indicated that two ARPs and α-DCs of m/z 235 were significantly up-regulated in AH. Meanwhile, the straightforward differentiation between naturally matured honey (NH) and AH was achieved by nanoESI-MS fingerprints combined with multivariate analysis. The method may provide a rapid characterization of Maillard reaction products (MRPs), which exhibits the great application potential in other complex food matrix.

Screening the Degradation of Polymer Microparticles on a Chip.

Enzymatic degradation of polymers has advantages over standard degradation methods, such as soil burial and weathering, which are time-consuming and cannot provide time-resolved observations. We have developed a microfluidic device to study the degradation of single microparticles. The enzymatic degradation of poly (1,4-butylene adipate-co-terephthalate) (PBAT) microparticles was studied using Novozym 51032 cutinase. PBAT microparticles were prepared via an oil-in-water emulsion solvent removal method, and their morphology and chemical composition were characterized. Then, microparticles with varying diameters of 30-60 µm were loaded into the microfluidic chip. Enzyme solutions at different concentrations were introduced to the device, and changes in the size and transparency of PBAT microparticles were observed over time. The physicochemical properties of degraded products were analyzed by FT-IR, NMR, mass spectrometry, and differential scanning calorimetry. The degradation process was also performed in bulk, and the results were compared to those of the microfluidic method. Our analysis confirms that the degradation process in both bulk and microfluidic methods was similar. In both cases, degradation takes place on aliphatic and soft segments of PBAT. Our findings serve as a proof of concept for a microfluidic method for easy and time-resolved degradation analysis, with degradation results comparable to those of conventional bulk methods.

mir-204-5p Acts as a Tumor Suppressor by Targeting DNM2 in Osteosarcoma Cells.

Osteosarcoma is a malignant bone tumor composed of interstitial cells. We aim to seek the function of mir-204-5p/DNM2 in osteosarcoma cells. From April 2017 to August 2019, 58 cases of cancer tissues and paracancer tissues were obtained from patients with osteosarcoma in our hospital. qPCR was used to detect mir-204-5p in excisional cancer tissues and paracarcinoma tissues of osteosarcoma patients. The overexpression vector of mir-204-5p was established and transfected into osteosarcoma cells, and the propagation, invasiveness, migration, and apoptosis of osteosarcoma cells were observed. StarBase was employed to forecast the binding site of mir-204-5p and DNM2. The targeting connection of mir-204-5p with DNM2 was detected via double luciferase reporter gene. mir-204-5p was lessened in osteosarcoma (p < 0.05). mir-204-5p overexpression suppressed propagation and accelerated apoptosis of osteosarcoma cells (p < 0.05). The results of double luciferase reporter gene revealed that the fluorescence activity of mir-204-5p was obviously declined when binding to DNM2 (p < 0.05). mir-204-5p functions as a tumor inhibitor by targeting DNM2 in osteosarcoma cells. Our research is helpful to provide new ideas for clinical treatment.

HDAC10 Is Positively Associated With PD-L1 Expression and Poor Prognosis in Patients With NSCLC.

Currently, non-small cell lung carcinoma (NSCLC) is a major worldwide health problem. Meanwhile accumulating evidence indicates that histone deacetylase (HDAC) activation could induce PD-L1 expression in various types of cancer, especially in myeloma and B-cell lymphomas. Therefore, we hypothesized that high-level expression of HDAC10 is associated with PD-L1 induction and poor prognosis in patients with NSCLC. In total 180 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection were enrolled from April 2004 to August 2009. The patients with integrated clinicopathological records were followed up. The expression level of HDAC10 and PD-L1 in tissue samples was determined by immunohistochemistry. We observed that HDAC10 expression in lung cancer tissue is significantly higher than that in corresponding para-cancer tissue. Moreover, HDAC10 expression positively correlated with the expression level of PD-L1 (r = 0.213, P < 0.05) in NSCLC patients. Subgroup, multivariate analysis showed that the expression level of HDAC10 can be an independent prognostic factor and high-level expression of HDAC10 indicated poor overall survival for pulmonary carcinoma (r = 0.540, P < 0.001). Our findings suggest that the expression level of HDAC10 is positively associated with PD-L1 expression and may predict the outcome of patients with NSCLC.

Advances in Artificial Layers for Stable Lithium Metal Anodes.

Lithium (Li) metal is considered as the most promising anode material for rechargeable high-energy batteries. Nevertheless, the practical implement of Li anodes is significantly hindered by the growth of Li dendrites, which can cause severe safety issues. To inhibit the formation of Li dendrites, coating an artificial layer on the Li metal anode has been shown to be a facile and effective approach. This review mainly focuses on recent advances in artificial layers for stable Li metal anodes. It summarizes the progress in this area and discusses the different types of artificial layers according to their mechanisms for Li dendrite inhibition, including regulation of uniform deposition of Li metal and suppression of Li dendrite growth. By doing this, it is hoped that this contribution will provide instructional guidance for the future design of new artificial layers.

High-Throughput Monitoring of Multiclass Syrup Adulterants in Honey Based on the Oligosaccharide and Polysaccharide Profiles by MALDI Mass Spectrometry.

Honey is a natural product that could be easily adulterated with various cheaper sweeteners. In the present study, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was applied for the detection of honey adulteration based on oligosaccharide and polysaccharide profiles. MS-based strategy could reveal the presence of polysaccharides with higher degree of polymerization (DP ≥ 13) and abnormal trends of saccharides in adulterated honey samples, which could be used as indicators for the identification of honey adulteration with high-fructose corn syrup and corn syrup. MS/MS-based strategy was proposed to characterize the difference in the composition of oligosaccharide isomers between honey samples and adulterated ones with corn syrup or invert syrup, in which the [M+Cl]- of disaccharides, trisaccharides, and tetrasaccharides were fragmented to give diagnostic product ion pairs. The method is effective and robust for the high-throughput monitoring of honey adulteration, and provides a new perspective for the identification of other high-carbohydrate foods.

Controllable Fabrication of Inhomogeneous Microcapsules for Triggered Release by Osmotic Pressure.

Inhomogeneous microcapsules that can encapsulate various cargo for controlled release triggered by osmotic shock are designed and reported. The microcapsules are fabricated using a microfluidic approach and the inhomogeneity of shell thickness in the microcapsules can be controlled by tuning the flow rate ratio of the middle phase to the inner phase. This study demonstrates the swelling of these inhomogeneous microcapsules begins at the thinnest part of shell and eventually leads to rupture at the weak spot with a low osmotic pressure. Systematic studies indicate the rupture fraction of these microcapsules increases with increasing inhomogeneity, while the rupture osmotic pressure decreases linearly with increasing inhomogeneity. The inhomogeneous microcapsules are demonstrated to be impermeable to small probe molecules, which enables long-term storage. Thus, these microcapsules can be used for long-term storage of enzymes, which can be controllably released through osmotic shock without impairing their biological activity. The study provides a new approach to design effective carriers to encapsulate biomolecules and release them on-demand upon applying osmotic shock.

An Interfacial Layer Based on Polymers of Intrinsic Microporosity to Suppress Dendrite Growth on Li Metal Anodes.

The performance and safety of lithium (Li) metal batteries can be compromised owing to the formation of Li dendrites. Here, the use of a polymer of intrinsic microporosity (PIM) is reported as a feasible and robust interfacial layer that inhibits dendrite growth. The PIM demonstrates excellent film-forming ability, electrochemical stability, strong adhesion to a copper metal electrode, and outstanding mechanical flexibility so that it relieves the stress of structural changes produced by reversible lithiation. Importantly, the porous structure of the PIM, which guides Li flux to obtain uniform deposition, and its strong mechanical strength combine to suppress dendrite growth. Hence, the electrochemical performance of the anode is significantly enhanced, promising excellent performance and extended cycle lifetime for Li metal batteries.

Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression.

Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.

Natural hydrogel in American lobster: A soft armor with high toughness and strength.

Homarus americanus, known as American lobster, is fully covered by its exoskeleton composed of rigid cuticles and soft membranes. These soft membranes are mainly located at the joints and abdomen to connect the rigid cuticles and greatly contribute to the agility of the lobster in swimming and preying. Herein, we show that the soft membrane from American lobster is a natural hydrogel (90% water) with exceptionally high toughness (up to 24.98 MJ/m3) and strength (up to 23.36 MPa), and is very insensitive to cracks. By combining experimental measurements and large-scale computational modeling, we demonstrate that the unique multilayered structure in this membrane, achieved through the ordered arrangement of chitin fibers, plays a crucial role in dissipating energy during rupture and making this membrane tough and damage tolerant. The knowledge learned from the soft membrane of natural lobsters sheds light on designing synthetic soft, yet strong and tough materials for reliable usage under extreme mechanical conditions, including a flexible armor that can provide full-body protection without sacrificing limb mobility. STATEMENT OF SIGNIFICANCE: A body armor to provide protection to people who are at risk of being hurt is only enabled by using a material that is tough and strong enough to prevent mechanical penetration. However, most modern body armors sacrifice limb protection to gain mobility, simply because none of the existing armor materials are flexible enough and they all inhibit movement of the arms and legs. Herein, we focus on the mechanics and mesoscopic structure of American lobsters' soft membrane and explore how such a natural flexible armor is designed to integrate flexibility and toughness. The knowledge learned from this study is useful to design a flexible armor for full-body protection under extreme mechanical conditions.

Microfluidic fabrication of microparticles for biomedical applications.

Droplet microfluidics offers exquisite control over the flows of multiple fluids in microscale, enabling fabrication of advanced microparticles with precisely tunable structures and compositions in a high throughput manner. The combination of these remarkable features with proper materials and fabrication methods has enabled high efficiency, direct encapsulation of actives in microparticles whose features and functionalities can be well controlled. These microparticles have great potential in a wide range of bio-related applications including drug delivery, cell-laden matrices, biosensors and even as artificial cells. In this review, we briefly summarize the materials, fabrication methods, and microparticle structures produced with droplet microfluidics. We also provide a comprehensive overview of their recent uses in biomedical applications. Finally, we discuss the existing challenges and perspectives to promote the future development of these engineered microparticles.

Gold Nanorods Conjugated Porous Silicon Nanoparticles Encapsulated in Calcium Alginate Nano Hydrogels Using Microemulsion Templates.

Porous silicon nanoparticles (PSiNPs) and gold nanorods (AuNRs) can be used as biocompatible nanocarriers for delivery of therapeutics but undesired leakage makes them inefficient. By encapsulating the PSiNPs and AuNRs in a hydrogel shell, we create a biocompatible functional nanocarrier that enables sustained release of therapeutics. Here, we report the fabrication of AuNRs-conjugated PSi nanoparticles (AuNRsPSiNPs) through two-step chemical reaction for high-capacity loading of hydrophobic and hydrophilic therapeutics with photothermal property. Furthermore, using water-in-oil microemulsion templates, we encapsulate the AuNRsPSiNPs within a calcium alginate hydrogel nanoshell, creating a versatile biocompatible nanocarrier to codeliver therapeutics for biomedical applications. We find that the functionalized nanohydrogel effectively controls the release rate of the therapeutics while maintaining a high loading efficiency and tunable loading ratios. Notably, combinations of therapeutics coloaded in the functionalized nanohydrogels significantly enhance inhibition of multidrug resistance through synergism and promote faster cancer cell death when combined with photothermal therapy. Moreover, the AuNRs can mediate the conversion of near-infrared laser radiation into heat, increasing the release of therapeutics as well as thermally inducing cell damage to promote faster cancer cell death. Our AuNRsPSiNPs functionalized calcium alginate nanohydrogel holds great promise for photothermal combination therapy and other advanced biomedical applications.

Graphene-based nanomaterials for drug and/or gene delivery, bioimaging, and tissue engineering.

Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their biomedical applications. We also summarize the detailed biomedical applications of GBNs, including drug and/or gene delivery, bioimaging, and tissue engineering. We also highlight the toxicity of these nanomaterials.

Large-scale orientation in a vulcanized stretched natural rubber network: proved by in situ synchrotron X-ray diffraction characterization.

In situ studies of strain-induced crystallization in unfilled and multiwalled carbon nanotube (MWCNT)-filled natural rubber (NR) were carried out by using synchrotron wide-angle X-ray diffraction (WAXD). Synchrotron WAXD results indicate that more nuclei appear in the MWCNT-filled NR sample, leading to higher crystallinity, lower onset strain of crystallization, and remarkable enhancement in tensile strength. During deformation, despite the amorphous chains remaining in isotropic orientation, the domains of larger scale (10-100 nm) with high network chain density in the NR matrix are oriented. The MWCNTs induce significant variation of this orientational process, and it is monitored by the stearic acid (SA) crystallites, which are effective nanoprobes of the amorphous phase. The results indicate that a small amount of MWCNTs and SA crystallites can be used as new tools to analyze the microstructural orientation of NR during deformation. The results also yield new insight into the strain-induced crystallization mechanism.