Mechanism of Cationic Lipid Induced DNA Condensation: Lipid-DNA Coordination and Divalent Cation Charge Fluctuations.

The condensation of nucleic acids by lipids is a widespread phenomenon in biology with crucial implications for drug delivery. However, the mechanisms of DNA assembly in lipid bilayers remain insufficiently understood due to challenges in measuring and assessing each component's contribution in the lipid-DNA-cation system. This study uses all-atom molecular dynamics simulations to investigate DNA condensation in cationic lipid bilayers. Our exhaustive exploration of the thermodynamic factors reveals unique roles for phospholipid head groups and cations. We observed that bridging cations between lipid and DNA drastically reduce charges, while mobile magnesium cations "ping-ponging" between double strands create charge fluctuations. While the first factor stabilizes the DNA-lipid complex, the latter creates attractive forces to induce the spontaneous condensation of DNAs. This novel mechanism not only sheds light on the current data regarding cationic lipid-induced DNA condensation but also provides potential design strategies for creating efficient gene delivery vectors for drug delivery.

Lactobacilli and Their Fermented Foods as a Promising Strategy for Enhancing Bone Mineral Density: A Review.

Lactobacilli fermentation possesses special nutritional and health values to food, especially in improving diseases related to the gut microbiota such as osteoporosis risk. Previous research indicates that lactobacilli-fermented foods have the potential to enhance the bone mineral density (BMD), as suggested by some clinical studies. Nonetheless, there is currently a lack of comprehensive summaries of the effects and potential mechanisms of lactobacilli-fermented foods on BMD. This review summarizes findings from preclinical and clinical studies, revealing that lactobacilli possess the potential to mitigate age-related and secondary factor-induced bone loss. Furthermore, these findings imply that lactobacilli are likely mediated through the modulation of bone remodeling via gut inflammation-related pathways. Additionally, lactobacilli fermentation may augment calcium accessibility through directly promoting calcium absorption or modifying food constituents. Considering the escalating global health challenge of bone-related issues among the elderly population, this review may offer a valuable reference for the development of food strategies aimed at preventing osteoporosis.

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Digital economy, technological innovation, and sustainable development.

This paper examines the impact of the digital economy on sustainable development, using panel data from cities at the prefecture level and above in China from 2011 to 2019. The results indicate: (1) The digital economy is conducive to boosting growth, increasing employment, reducing energy consumption, and cutting emissions, thereby promoting sustainable development. These findings prove robust. (2) Mechanism test outcomes reveal that, from the perspective of technological innovation, the digital economy can promote sustainable development through increasing R&D input and enhancing innovation output. (3) An extended analysis of the risk of a digital "divide" demonstrates that "dividend" of the digital economy is primarily manifests in spurring economic growth, enhancing energy efficiency, and strengthening environmental protection in lagging regions, while the digital "divide" effect is manifested in the stronger employment stimulating effect of developed regions versus backward areas. The results of this study not only enrich the relevant research system, but also provide empirical evidence to support accelerating digital transformation, strengthening technological innovation governance, and advancing sustainable development.

Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a centromere-specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

Insights into dynamic evolution of glucuronofucogalactoglucan from water extract of Agrocybe cylindracea during maturation.

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.

Changes of the Physicochemical Properties and Structural Characteristics of Alkali-Extracted Polysaccharides from Agrocybe cylindracea Across the Growth Process.

Polysaccharides derived from Agrocybe cylindracea have been demonstrated to exhibit various bioactivities. However, studies on their structural characteristics during the growth process are limited. This study aimed to compare the physicochemical properties and structural characteristics of alkali-extracted polysaccharides from A. cylindracea fruiting bodies (JACP) across four growth stages. Results showed that the extraction yields and protein levels of JACP declined along with the growth of A. cylindracea, while the contents of neutral sugar and glucose increased significantly. However, JACP exhibited structural characteristics similar to those across the four stages. Four polysaccharide subfractions were isolated from each growth stage, including JACP-Et30, JACP-Et50, JACP-Et60, and JACP-Et70. JACP-Et30 from the four stages and JACP-Et50 from the initial three stages were identified as heteroglucans with ß-1,3-d-Glcp and ß-1,6-d-Glcp residues as main chains, respectively. However, other subfractions were considered as ß-1,6-d-glucans containing minor glucuronic acid. These subfractions were predominantly replaced by Glcp residues at the O-3 and O-6 positions. Overall, while JACP exhibited variable physicochemical properties, its structural characteristics remained stable during the growth process, offering new insights into its potential applications in the food and medicinal industries.

Exploring the Biogenic Transformation Mechanism of Polyphenols by Lactobacillus plantarum NCU137 Fermentation and Its Enhancement of Antioxidant Properties in Wolfberry Juice.

This study investigated the transformation of polyphenols, including free and bound polyphenols during the fermentation of wolfberry juice by Lactobacillus plantarum NCU137. Results indicated that fermentation significantly increased the free polyphenols content and released bound polyphenols, enhancing the antioxidant activity. Analysis showed that there were 19 free polyphenols, mainly scopoletin, pyrogallol, and dihydroferulic acid, and 16 bound polyphenols, especially p-coumaric acid, feruloyl hexoside, and caffeic acid. A significant correlation was observed between the generation and degradation of polyphenols, and specific bound polyphenols peaked during the 24-48 h fermentation. Furthermore, reduced surface roughness and galacturonic acid content in wolfberry residue, along with increased pectinase activity, suggested substantial pectin degradation in the cell wall, which may be associated with the release of polyphenols, due to pectin serving as carriers for bound polyphenols. The fermentation also increased polyphenol oxidase and peroxidase activity, contributing to polyphenol breakdown. These findings provide insights for improving wolfberry juice production.

The Emulsification and Stabilization Mechanism of an Oil-in-Water Emulsion Constructed from Tremella Polysaccharide and Citrus Pectin.

The objective of this study was to investigate the feasibility of the mixture of tremella polysaccharide (TP) and citrus pectin (CP) as an emulsifier by evaluating its emulsifying ability/stability. The results showed that the TP:CP ratio of 5:5 (w/w) could effectively act as an emulsifier. CP, owing its lower molecular weight and highly methyl esterification, facilitated the emulsification of oil droplets, thereby promoting the dispersion of droplets. Meanwhile, the presence of TP enhanced the viscosity of emulsion system and increased the electrostatic interactions and steric hindrance, therefore hindering the migration of emulsion droplets, reducing emulsion droplets coalesce, and enhancing emulsion stability. The emulsification and stabilization performances were influenced by the molecular weight, esterified carboxyl groups content, and electric charge of TP and CP, and the potential mechanism involved their impact on the buoyant force of droplet size, viscosity, and steric hindrance of emulsion system. The emulsions stabilized by TP-CP exhibited robust environmental tolerance, but demonstrated sensitivity to Ca2+. Conclusively, the study demonstrated the potential application of the mixture of TP and CP as a natural polysaccharide emulsifier.

Revolutionizing digestive system tumor organoids research: Exploring the potential of tumor organoids.

Digestive system tumors are the leading cause of cancer-related deaths worldwide. Despite ongoing research, our understanding of their mechanisms and treatment remain inadequate. One promising tool for clinical applications is the use of gastrointestinal tract tumor organoids, which serve as an important in vitro model. Tumor organoids exhibit a genotype similar to the patient's tumor and effectively mimic various biological processes, including tissue renewal, stem cell, and ecological niche functions, and tissue response to drugs, mutations, or injury. As such, they are valuable for drug screening, developing novel drugs, assessing patient outcomes, and supporting immunotherapy. In addition, innovative materials and techniques can be used to optimize tumor organoid culture systems. Several applications of digestive system tumor organoids have been described and have shown promising results in related aspects. In this review, we discuss the current progress, limitations, and prospects of this model for digestive system tumors.

Ascorbic acid-mediated reduction of arabinoxylan viscosity through free radical reactions.

Arabinoxylan (AX) is a potential natural food additive that can enhance the textural properties of food. However, the addition of ascorbic acid (AA) can easily lead to a decrease in the viscosity of AX, which poses a challenge in the development of AX-rich foods. Therefore, the purpose of this study is to elucidate the mechanisms behind the reduction in AX viscosity in the presence of AA. The results indicated that AA could reduce the apparent viscosity and molecular weight of AX without significantly affecting the monosaccharide composition, suggesting a potential mechanism related to the cleavage of AX glycosidic bonds. Interestingly, free radicals were present in the reaction system, and the generation of free radicals under different conditions was consistent with the reduction in apparent viscosity of AX. Furthermore, the reduction in AX apparent viscosity by AA was influenced by various factors including AA concentration, reaction time, temperature, pH, and metal ions. These findings suggested that the mechanism of AX degradation may be due to AA-induced free radical generation, leading to non-selective attacks on glycosidic bonds. Therefore, this study revealed that the potential mechanism behind the reduction in AX viscosity induced by AA involved the generation of ascorbic acid radicals.

Exploration and Improvement of Acid Hydrolysis Conditions for Inulin-Type Fructans Monosaccharide Composition Analysis: Monosaccharide Recovery and By-Product Identification.

Acid hydrolysis serves as the primary method for determining the monosaccharide composition of polysaccharides. However, inappropriate acid hydrolysis conditions may catalyze the breakdown of monosaccharides such as fructans (Fru), generating non-sugar by-products that affect the accuracy of monosaccharide composition analysis. In this study, we determined the monosaccharide recovery rate and non-sugar by-product formation of inulin-type fructan (ITF) and Fru under varied acid hydrolysis conditions using HPAEC-PAD and UPLC-Triple-TOF/MS, respectively. The results revealed significant variations in the recovery rate of Fru within ITF under different hydrolysis conditions, while glucose remained relatively stable. Optimal hydrolysis conditions for achieving a relatively high monosaccharide recovery rate for ITF entailed 80 °C, 2 h, and 1 M sulfuric acid. Furthermore, we validated the stability of Fru during acid hydrolysis. The results indicated that Fru experienced significant degradation with an increasing temperature and acid concentration, with a pronounced decrease observed when the temperature exceeds 100 °C or the H2SO4 concentration surpasses 2 M. Finally, three common by-products associated with Fru degradation, namely 5-hydroxymethyl-2-furaldehyde, 5-methyl-2-furaldehyde, and furfural, were identified in both Fru and ITF hydrolysis processes. These findings revealed that the degradation of Fru under acidic conditions was a vital factor leading to inaccuracies in determining the Fru content during ITF monosaccharide analysis.

Abundance of Modifications in Mature miRNAs Revealed by LC-MS/MS Method Coupled with a Two-Step Hybridization Purification Strategy.

Accurate detection of endogenous miRNA modifications, such as N6-methyladenosine (m6A), 7-methylguanosine (m7G), and 5-methylcytidine (m5C), poses significant challenges, resulting in considerable uncertainty regarding their presence in mature miRNAs. In this study, we demonstrate for the first time that liquid chromatography coupled with a tandem mass spectrometry (LC-MS/MS) nucleoside analysis method is a practical tool for quantitatively analyzing human miRNA modifications. The newly designed liquid-solid two-step hybridization (LSTH) strategy enhances specificity for miRNA purification, while LC-MS/MS offers robust capability in recognizing modifications and sufficient sensitivity with detection limits ranging from attomoles to low femtomoles. Therefore, it provides a more reliable approach compared to existing techniques for revealing modifications in endogenous miRNAs. With this approach, we characterized m6A, m7G, and m5C modifications in miR-21-5p, Let-7a/e-5p, and miR-10a-5p isolated from cultured cells and observed unexpectedly low abundance (<1% at each site) of these modifications.

Dynamics of α-glucan from Agrocybe cylindracea water extract at different developmental stages and its structure characteristics.

Polysaccharides are the important bioactive macromolecules in Agrocybe cylindracea, but their changes are as yet elusive during developmental process. This study investigated the dynamic changes of polysaccharides from A. cylindracea fruiting body water extract at four developmental stages and its structure characteristics. Results revealed that the polysaccharides from A. cylindracea water extract significantly increased at the pileus expansion stage and the increased fraction could be α-glucan. The further purification and identification indicated that this α-glucan was a glycogen. It had typical morphology of ß particles with a molecular weight of 1375 kDa. Its backbone comprised α-D-(1 â†’ 4)-Glcp and α-D-(1 â†’ 4,6)-Glcp residues at a ratio of 5:1, terminated by α-D-Glcp residue. Rheological behavior suggested that it was a Newtonian fluid at the concentration of 1 %. In addition, despite both the glycogen and natural starch were composed of D-glucose, they exhibited the entirely distinct Maltese cross characteristic and unique crystalline structure. This study is the first to demonstrate the presence of abundant glycogen in the pileus expansion stage of A. cylindracea, which provides new insights on the change patterns of fungal polysaccharides.

2D Memory Selectors with Giant Nonlinearity Enabled by Van der Waals Heterostructures.

The integration of one-selector-one-resistor crossbar arrays requires the selectors featured with high nonlinearity and bipolarity to prevent leakage currents and any crosstalk among distinct cells. However, a selector with sufficient nonlinearity especially in the frame of device miniaturization remains scarce, restricting the advance of high-density storage devices. Herein, a high-performance memory selector is reported by constructing a graphene/hBN/WSe2 heterostructure. Within the temperature range of 300-80 K, the nonlinearity of this selector varies from ≈103 - ≈104 under forward bias, and increases from ≈300 - ≈105 under reverse bias, the highest reported nonlinearity among 2D selectors. This improvement is ascribed to direct tunneling at low bias and Fowler-Nordheim tunneling at high bias. The tunneling current versus voltage curves exhibit excellent bipolarity behavior because of the comparable hole and electron tunneling barriers, and the charge transport polarity can be effectively tuned from N-type or P-type to bipolar by simply changing source-drain bias. In addition, the conceptual memory selector exhibits no sign of deterioration after 70 000 switching cycles, paving the way for assembling 2D selectors into modern memory devices.

The effect of in vitro simulated colonic pH gradients on microbial activity and metabolite production using common prebiotics as substrates.

BACKGROUND: The interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon. RESULTS: Here we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates. CONCLUSIONS: Together, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research.

Effects of prolonged face mask use among patients with hypertension or diabetes during the COVID-19 pandemic.

OBJECTIVE: We aimed to investigate the impacts of prolonged mask use on patients with hypertension or diabetes during the COVID-19 pandemic. METHODS: This study included patients with hypertension or diabetes who visited the outpatient department of Nanjing Yimin Hospital between 1 February 2022 and 31 January 2023. We compared the change in blood pressure (BP) and fasting plasma glucose in patients with hypertension or diabetes and adjustments to treatment between the group with prolonged mask-wearing group (≥20 hours/week) and the control group (<20 hours/week). RESULTS: Compared with the control group of hypertensive patients, the prolonged mask-wearing group had significantly higher diastolic blood pressure (DBP) and mean arterial pressure (MAP). These two groups had had similar DBP and MAP 1 year earlier. Likewise, the prolonged mask-wearing group of patients with diabetes had a greater need than the control group for upgraded treatment to reach their therapeutic goals. CONCLUSIONS: This study suggests that prolonged mask use by patients with hypertension or diabetes has negative effects on hypertension and plasma glucose control. BP and plasma glucose monitoring should be improved in these patient populations and their treatment should be adjusted in a timely manner.

The impact of city size on income inclusive growth: A human capital perspective and evidence from China.

This paper methodically investigates the influence of inclusive income growth on city size, examining it through the dual lenses of "income" and "distribution." The analysis leverages meticulously collected panel data encompassing 276 Chinese cities at the prefecture level and above, spanning the period from 2005 to 2019. Theoretical analysis indicates that the effect of city size expansion on per capita income adheres to a 'U'-shaped trajectory, while its influence on the urban-rural income gap manifests an 'inverted U' pattern. Moreover, the inclusive income growth stemming from city size demonstrates notable heterogeneity across various geographic locations and city hierarchies. The findings reveal that human capital serves as the primary mechanism through which city size influences inclusive income growth. After decomposing the income inclusiveness index, it becomes evident that the expansion of city size exerts a more potent direct driving effect on the income of urban residents. On the one hand, city size expansion directly increases rural residents' income levels by improving labor productivity. On the other hand, it facilitates leapfrog income development by inducing the rural labor force to move to cities.

Copper regulation of PtRhRuCu nanozyme targeted boosting peroxidase-like activity for ultrasensitive smartphone-assisted colorimetric sensing of glucose.

Point-of-care testing (POCT) is promising for biodetection in home healthcare due to advantages of simplicity, rapidity, low cost, portability, high sensitivity and accuracy, and object-oriented POCT platform can be developed by nanozyme-based biosensing. However, designing high-performance nanozymes with targeted regulated catalytic activity remains challenging. Herein, advanced PtRhRuCu quaternary alloy nanozymes (QANs) were rationally designed and successfully synthesized. Cu atoms induced mechanisms of hydrogen peroxide (H2O2) activation and d-band center regulation, achieving high enhancement of peroxide (POD)-like activity and inhibition of oxidase (OXD)-like activity. Inspired by this, a smartphone-assisted colorimetric platform integrated with test strips was established for glucose detection of soft drinks, with a detection limit of 0.021 mM and a recovery rate of 97.87 to 103.36 %. This work not only provides a novel path for tuning specific enzyme-like activities of metal nanozymes, but also shows the potential feasibility for rational design of POCT sensors in actual samples.

[Research progress of rapid surgery for hip fracture in elderly patients].

Objective: To review the research progress of rapid surgery for hip fracture in elderly patients. Methods: The published studies, expert consensus, and guidelines at home and abroad were systematically summarized from the aspects of the characteristics of aging population, the benefits of rapid surgery, the disadvantages of delayed surgery, and the recommendations of current guidelines, so as to further guide clinical practice. Results: Hip fracture is a common fracture type in the elderly population. As elderly patients generally have poor physique and often have a variety of underlying diseases, such as hypostatic pneumonia, bedsore, lower limb vein thrombosis, and other complications in conservative treatment, its disability rate and mortality are high, so surgical treatment is the first choice. At present, most relevant studies and expert consensus and guidelines at home and abroad support rapid surgery, that is, preoperative examination should be started immediately after admission, and adverse factors such as taking anticoagulant drugs, serious cardiovascular diseases, and severe anemia should be clearly and actively corrected, and surgery should be completed within 48 hours after admission as far as possible. Rapid surgery can not only significantly reduce the mortality of patients, but also reduce the length of hospital stay and the incidence of perioperative cognitive impairment, which is conducive to the recovery of patients with pain during hospitalization and postoperative function, and improve the prognosis of patients. Conclusion: In order to avoid many problems caused by delayed surgery, the elderly patients with hip fracture should be operated as soon as possible under the condition of actively correcting the adverse factors. Comprehensive evaluation and preparation, the development of an individualized surgical plan, and the formation of a multidisciplinary medical team can reduce surgical risks and improve effectiveness.