Enhancing vitamin D3 bioaccessibility: Unveiling hydrophobic interactions in soybean protein isolate and vitamin D3 binding via an infant in vitro digestion model.

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D3 (VD3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (Ka = 0.166 × 105 L·mol-1) at 80 MPa and significant surface hydrophobicity (H0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD3 bioavailability. This investigation underscores the potential of SPI-VD3 nanoparticles in bolstering VD3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations.

Electrolytes Design for Extending the Temperature Adaptability of Lithium-Ion Batteries: from Fundamentals to Strategies.

With the continuously growing demand for wide-range applications, lithium-ion batteries (LIBs) are increasingly required to work under conditions that deviate from room temperature (RT). However, commercial electrolytes exhibit low thermal stability at high temperatures (HT) and poor dynamic properties at low temperatures (LT), hindering the operation of LIBs under extreme conditions. The bottleneck restricting the practical applications of LIBs has promoted researchers to pay more attention to developing a series of innovative electrolytes. This review primarily covers the design of electrolytes for LIBs from a temperature adaptability perspective. First, the fundamentals of electrolytes concerning temperature, including donor number (DN), dielectric constant, viscosity, conductivity, ionic transport, and theoretical calculations are elaborated. Second, prototypical examples, such as lithium salts, solvent structures, additives, and interfacial layers in both liquid and solid electrolytes, are presented to explain how these factors can affect the electrochemical behavior of LIBs at high or low temperatures. Meanwhile, the principles and limitations of electrolyte design are discussed under the corresponding temperature conditions. Finally, a summary and outlook regarding electrolytes design to extend the temperature adaptability of LIBs are proposed.

Wide-Temperature and High-Rate Operation of Lithium Metal Batteries Enabled by an Ionic Liquid Functionalized Quasi-Solid-State Electrolyte.

The development of high-energy-density solid-state lithium metal battery has been hindered by the unstable cycling of Ni-rich cathodes at high rate and limited wide-temperatures adoptability. In this study, an ionic liquid functionalized quasi-solid-state electrolyte (FQSE) is prepared to address these challenges. The FQSE features a semi-immobilized ionic liquid capable of anchoring solvent molecules through electrostatic interactions, which facilitates Li+ desolvation and reduces deleterious solvent-cathode reactions. The FQSE exhibits impressive electrochemical characteristics, including high ionic conductivity (1.9 mS cm-1 at 30 °C and 0.2 mS cm-1 at -30 °C) and a Li+ transfer number of 0.7. Consequently, Li/NCM811 cells incorporating FQSE demonstrate exceptional stability during high-rate cycling, enduring 700 cycles at 1 C. Notably, the Li/LFP cells with FQSE maintain high capacity across a wide temperature range, from -30 to 60 °C. This research provides a new way to promote the practical application of high-energy lithium metal batteries.

The function of carnosic acid in lipopolysaccharides-induced hepatic and intestinal inflammation in poultry.

Inflammatory processes are often accompanied by oxidative stress and lipid peroxidation, which might lead to cellular and organ damage. Carnosic acid (CA), an active component found in rosemary, exhibits pharmacological properties including antioxidative, anti-inflammatory, and antiviral effects. The aim of this research was to investigate whether CA can mitigate lipopolysaccharide (LPS)-induced oxidative stress and inflammatory responses in poultry and to understand its underlying mechanisms. We administered CA to broiler chickens via oral gavage and treated them with LPS, followed by analysis of the effects of different dosages of CA on body weight, antioxidative capacity, and inflammatory factors. Carnosic acid had no significant impact on the body weight of broiler chickens. However, serum analysis indicated that the middle dose of CA effectively enhanced the antioxidative capacity and reduced levels of oxidative stress and inflammation-related factors. Moreover, in the liver, CA demonstrated the ability to regulate the expression of proteins such as heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and P38 mitogen-activated protein kinase (P38), suggesting its protective role against liver damage induced by LPS. In the intestinal tract of broiler chickens, CA regulated the expression and localization of proteins including HSP60, HSP70, NFE2 like bZIP transcription factor 2 (Nrf2), and P38, while also influencing the expression of inflammatory markers such as protein tyrosine phosphatase receptor type C (CD45), and connexin (Cx). These findings revealed the potential protective mechanisms of CA in alleviating oxidative stress and inflammatory damage induced by LPS in poultry. Carnosic acid notably enhanced the chickens' antioxidative capacity by modulating the expression of key proteins, thereby reducing oxidative stress and inflammatory response levels. This study provides a deeper comprehension of the protective mechanisms of CA and its potential impact on avian health.

Metagenomics next-generation sequencing (mNGS) reveals emerging infection induced by Klebsiella pneumoniaeniae.

OBJECTIVES: The increasing emergence of hypervirulent Klebsiella pneumoniae (hv-Kp) and carbapenem-resistant K. pneumoniae (CR-Kp) is a serious and substantial public health problem. The use of the last resort antimicrobials, tigecycline and polymyxin to combat infections is complicated by the expanding repertoire of newly-identified CR-hvKp. The transmission and co-occurrence of the corresponding antimicrobial resistance and virulence determinants are largely unknown. The aim of this study was to investigate the dissemination and dynamics of CR-Kp and its antibiotic resistance in a hospitalised patient. METHODS: Metagenomic next-generation sequencing (mNGS) was conducted for different specimens collected from an elderly male hospitalised patient. CR-Kp strains were examined using antibiotic susceptibility and string testing. Antimicrobial and virulence genes were annotated using whole-genome sequencing (WGS). RESULTS: A clinical case of a patient infected with a variety of CR-Kp isolates was reported. The co-occurrence of KPC-2 and NDM-1 in the patient was revealed. The CR-Kp isolates, such as BALF2, and Sputum T1 and T3, were classified into ST11 and ST147, respectively. The genetic signature (iuc operon) of hypervirulence was identified in strain T1, although string testing indicated its intermediate virulence. CONCLUSIONS: In this study, multiple infections of CR-Kp isolates were revealed by mNGS, and their dissemination was attributed to plasmid variations, mgrB inactivation and integrative conjugative elements (ICEs). Furthermore, the finding indicated one likely convergence to form CR-hvKp, different from acquisition of carbapenem-resistance determinants in hvKp. A combination of mNGS and WGS is beneficial for clinical diagnosis and anti-infection therapy, and facilitates a better understanding of genetic variants conferring antimicrobial and virulence properties.

The telomere-to-telomere gap-free reference genome of wild blueberry (Vaccinium duclouxii) provides its high soluble sugar and anthocyanin accumulation.

Vaccinium duclouxii, endemic to southwestern China, is a berry-producing shrub or small tree belonging to the Ericaceae family, with high nutritive, medicinal, and ornamental value, abundant germplasm resources, and good edible properties. In addition, V. duclouxii exhibits strong tolerance to adverse environmental conditions, making it a promising candidate for research and offering wide-ranging possibilities for utilization. However, the lack of V. duclouxii genome sequence has hampered its development and utilization. Here, a high-quality telomere-to-telomere genome sequence of V. duclouxii was de novo assembled and annotated. All of 12 chromosomes were assembled into gap-free single contigs, providing the highest integrity and quality assembly reported so far for blueberry. The V. duclouxii genome is 573.67 Mb, which encodes 41 953 protein-coding genes. Combining transcriptomics and metabolomics analyses, we have uncovered the molecular mechanisms involved in sugar and acid accumulation and anthocyanin biosynthesis in V. duclouxii. This provides essential molecular information for further research on the quality of V. duclouxii. Moreover, the high-quality telomere-to-telomere assembly of the V. duclouxii genome will provide insights into the genomic evolution of Vaccinium and support advancements in blueberry genetics and molecular breeding.

Characteristics of cardiac arrhythmia and heart rate variability in Chinese patients with primary aldosteronism.

We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

Reductive Competition Effect-Derived Solid Electrolyte Interphase with Evenly Scattered Inorganics Enabling Ultrahigh Rate and Long-Life Span Sodium Metal Batteries.

Constructing an inorganic-rich and robust solid electrolyte interphase (SEI) is one of the crucial approaches to improving the electrochemical performance of sodium metal batteries (SMBs). However, the low conductivity and distribution of common inorganics in SEI disturb Na+ diffusion and induce nonuniform sodium deposition. Here, we construct a unique SEI with evenly scattered high-conductivity inorganics by introducing a self-sacrifice LiTFSI into the sodium salt-base carbonate electrolyte. The reductive competition effect between LiTFSI and FEC facilitates the formation of the SEI with evenly scattered inorganics. In which the high-conductive Li3N and inorganics provide fast ions transport domains and high-flux nucleation sites for Na+, thus conducive to rapid sodium deposition at a high rate. Therefore, the SEI derived from LiTFSI and FEC enables the Na∥Na3V2(PO4)3 cell to show 89.15% capacity retention (87.62 mA h g-1) at an ultrahigh rate of 60 C after 10,000 cycles, while the cell without LiTFSI delivers only 48.44% capacity retention even after 8000 cycles. Moreover, the Na∥Na3V2(PO4)3 pouch cell with the special SEI presents a stable capacity retention of 92.05% at 10 C after 2000 cycles. This unique SEI design elucidates a new strategy to propel SMBs to operate under extreme high-rate conditions.

Zoonotic pathogens identified in rodents and shrews from four provinces, China, 2015-2022.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Size-Controllable Nanosystem with Double Responsive for Deep Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, a poor tissue penetration of activation light and low target specificity seriously hindered the clinical application of PDT. Here, we designed and constructed a size-controllable nanosystem (UPH) with inside-out responsive for deep PDT with enhanced biosafety. To obtain nanoparticles with the best quantum yield, a series of core-shell nanoparticles (UCNP@nPCN) with different thicknesses were synthesized by a layer-by-layer self-assembly method to incorporate a porphyritic porous coordination network (PCN) onto the surface of upconverting nanoparticles (UCNPs), followed by coating with hyaluronic acid (HA) on the surface of nanoparticles with optimized thickness to form the UPH nanoparticles. With the aid of HA, the UPH nanoparticles were capable of preferentially enriching in tumor sites and specific endocytosis by CD44 receptors as well as responsive degradation by hyaluronidase in cancer cells after intravenous administration. Subsequently, after being activated by strong penetrating 980 nm near-infrared light (NIR), the UPH nanoparticles efficiently converted oxygen into strongly oxidizing reactive oxygen species based on the fluorescence resonance energy transfer (FRET) effect, thereby significantly inhibiting tumor growth. Experimental results in vitro and in vivo indicated that such dual-responsive nanoparticles successfully realize the photodynamic therapy of deep-seated cancer with negligible side effects, which showed great potential for potential clinical translational research.

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice.

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

Evaluation and treatment strategy of limb length discrepancy after total hip arthroplasty / 中华外科杂志

Limb length discrepancy(LLD) is a common complication after total hip arthroplasty (THA). Good positioning of the prosthesis and suitable soft tissue tension are essential to ensure hip joint stability. Patients will be more satisfied if almost the same length of both lower extremities is achieved. Preoperative comprehensive evaluation of patients is helpful to prevent the occurrence of LLD after surgery. Therefore, the pelvic spine conditions, as well as type and cause of LLD should be analyzed in detail before surgery. During operation, limb length should be adjusted by touching the position of patella, Kirschner's wires positioning and referring to the relationship between the center of femoral head and the tip of greater trochanter. After surgery, it is necessary to clearly distinguish true LLD from functional LLD, and make a reasonable therapeutic plan according to patient's symptoms and the range of differences in limb length. This article reviews the latest literatures based on clinical practice experience and summarizes the research status of LLD after THA, which helps joint surgeons to have an in-depth understanding of this postoperative complication.

Thermodynamic and Kinetic Modulation of Microfluidic Interfaces by DNA Nanoassembly Mediated Merit-Complementary Heteromultivalency.

The multivalent effect is often used to engineer microfluidic affinity interfaces to improve the target separation efficiency. Currently, no design rules exist for thermodynamic and kinetic tuning of properly joining multiple ligands. Herein, we developed a thermodynamic and kinetic modulating strategy of the microfluidic affinity interface via a merit-complementary-heteromultivalent aptamers functionalized DNA nanoassembly. Our strategy is built on the two types of identified aptamers that bind to distinct sites of EpCAM. The aptamer binding of one type is more rapid but less tight, while the other is opposite. By assembling the two types of aptamers together with a tetrahedral DNA framework, we fully exploited these aptamers' merits for tight and rapid recognition of EpCAM, leading to target cell capture with high efficiency and throughput. Our strategy provides a perspective on engineering multivalent recognition molecules through thermodynamic and kinetic tuning.

Spatial- and Valence-Matched Neutralizing DNA Nanostructure Blocks Wild-Type SARS-CoV-2 and Omicron Variant Infection.

Natural ligand-receptor interactions that play pivotal roles in biological events are ideal models for design and assembly of artificial recognition molecules. Herein, aiming at the structural characteristics of the spike trimer and infection mechanism of SARS-CoV-2, we have designed a DNA framework-guided spatial-patterned neutralizing aptamer trimer for SARS-CoV-2 neutralization. The ∼5.8 nm tetrahedral DNA framework affords precise spatial organization and matched valence as four neutralizing aptamers (MATCH-4), which matches with nanometer precision the topmost surface of SARS-CoV-2 spike trimer, enhancing the interaction between MATCH-4 and spike trimer. Moreover, the DNA framework provides a dimensionally complementary nanoscale barrier to prevent the spike trimer-ACE2 interaction and the conformational transition, thereby inhibiting SARS-CoV-2-host cell fusion and infection. As a result, the spatial- and valence-matched MATCH-4 ensures improved binding affinity and neutralizing activity against SARS-CoV-2 and its varied mutant strains, particularly the current Omicron variant, that are evasive of the majority of existing neutralizing antibodies. In addition, because neutralizing aptamers specific to other targets can be evolved and assembled, the present design has the potential to inhibit other wide-range and emerging pathogens.

Mechanosensing view of SARS-CoV-2 infection by a DNA nano-assembly.

The mechanical force between a virus and its host cell plays a critical role in viral infection. However, characterization of the virus-cell mechanical force at the whole-virus level remains a challenge. Herein, we develop a platform in which the virus is anchored with multivalence-controlled aptamers to achieve transfer of the virus-cell mechanical force to a DNA tension gauge tether (Virus-TGT). When the TGT is ruptured, the complex of binding module-virus-cell is detached from the substrate, accompanied by decreased host cell-substrate adhesion, thus revealing the mechanical force between whole-virus and cell. Using Virus-TGT, direct evidence about the biomechanical force between SARS-CoV-2 and the host cell is obtained. The relative mechanical force gap (<10 pN) at the cellular level between the wild-type virus to cell and a variant virus to cell is measured, suggesting a possible positive correlation between virus-cell mechanical force and infectivity. Overall, this strategy provides a new perspective to probe the SARS-CoV-2 mechanical force.

Synergistic Stimulation of Metal-Organic Frameworks for Stable Super-cooled Liquid and Quenched Glass.

Metal-organic framework (MOF) glasses are a fascinating new class of materials, yet their prosperity has been impeded by the scarcity of known examples and limited vitrification methods. In the work described in this report, we applied synergistic stimuli of vapor hydration and thermal dehydration to introduce structural disorders in interpenetrated dia-net MOF, which facilitate the formation of stable super-cooled liquid and quenched glass. The material after stimulus has a glass transition temperature (Tg) of 560 K, far below the decomposition temperature of 695 K. When heated, the perturbed MOF enters a super-cooled liquid phase that is stable for a long period of time (>104 s), across a broad temperature range (26 K), and has a large fragility index of 83. Quenching the super-cooled liquid gives rise to porous MOF glass with maintained framework connectivity, confirmed by EXAFS and PDF analysis. This method provides a fundamentally new route to obtain glassy materials from MOFs that cannot be melted without causing decomposition.

Spatially Patterned Neutralizing Icosahedral DNA Nanocage for Efficient SARS-CoV-2 Blocking.

Broad-spectrum anti-SARS-CoV-2 strategies that can inhibit the infection of wild-type and mutant strains would alleviate their threats to global public health. Here, we propose an icosahedral DNA framework for the assembly of up to 30 spatially arranged neutralizing aptamers (IDNA-30) to inhibit viral infection. Each triangular plane of IDNA-30 is composed of three precisely positioned aptamers topologically matching the SARS-CoV-2 spike trimer, thus forming a multivalent spatially patterned binding. Due to its multiple binding sites and moderate size, multifaced IDNA-30 induces aggregation of viruses. The rigid icosahedron framework afforded by four helixes not only forms a steric barrier to prevent the virus from binding to the host but also limits the conformational transformation of the SARS-CoV-2 spike trimer. Combining multivalent topologically patterned aptamers with structurally well-defined nanoformulations, IDNA-30 exhibits excellent broad-spectrum neutralization against SARS-CoV-2, including almost completely blocking the infection of Omicron pseudovirus. Overall, this multidimensional neutralizing strategy provides a new direction for the assembly of neutralizing reagents to enhance their inhibitory effect against SARS-CoV-2 infection and combat other disease-causing viruses.