Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78. To further explore the effect of DNFs on enantioseparation, different types of chiral columns including DNA strand containing the complementary sequence of the template (DCT)-modified CSMs, DNF2-modified CSMs, and DNF3-modified CSMs were prepared as well. It was observed that DNF-modified CSMs displayed better chiral separation ability compared with DCT-based columns. The intra-day and inter-day repeatability of model analytes' retention time and resolution kept desirable relative standard deviation values of less than 8.28%. DNF2/DNF3-modified CSMs were able to achieve baseline separation of atenolol, propranolol, 2'-deoxyadenosine, and nefopam enantiomers. Molecular docking simulations were performed to investigate enantioselectivity mechanisms of DNA sequences for enantiomers. To indicate the successful construction of DNFs and DNF-modified CSMs, various charaterization approaches including scanning electron microscopy, agarose gel electrophoresis, dynamic light scattering analysis, electroosmotic flow, and Fourier-transform infrared spectroscopy were utilized. Moreover, the enantioseparation performance of DNF-modified CSMs was characterized in terms of sample volume, applied voltage, and buffer concentration. This work paves the way to applying DNF-based capillary electrochromatography microsystems for chiral separation.

From individuals to families: design and application of self-similar chiral nanomaterials.

Establishing an intimate relationship between similar individuals is the beginning of self-extension. Various self-similar chiral nanomaterials can be designed using an individual-to-family approach, accomplishing self-extension. This self-similarity facilitates chiral communication, transmission, and amplification of synthons. We focus on describing the marriage of discrete cages to develop self-similar extended frameworks. The advantages of utilizing cage-based frameworks for chiral recognition, enantioseparation, chiral catalysis and sensing are highlighted. To further promote self-extension, fractal chiral nanomaterials with self-similar and iterated architectures have attracted tremendous attention. The beauty of a fractal family tree lies in its ability to capture the complexity and interconnectedness of a family's lineage. As a type of fractal material, nanoflowers possess an overarching importance in chiral amplification due to their large surface-to-volume ratio. This review summarizes the design and application of state-of-the-art self-similar chiral nanomaterials including cage-based extended frameworks, fractal nanomaterials, and nanoflowers. We hope this formation process from individuals to families will inherit and broaden this great chirality.

Exploring the Cryopreservation Mechanism and Direct Removal Strategy of TAPS in Red Blood Cell Cryopreservation.

Cryopreservation of red blood cells (RBCs) plays an indispensable role in modern clinical transfusion therapy. Researchers are dedicated to finding cryoprotectants (CPAs) with high efficiency and low toxicity to prevent RBCs from cryopreservation injury. This study presents, for the first time, the feasibility and underlying mechanisms of a novel CPA called tris(hydroxymethyl)aminomethane-3-propanesulfonic acid (TAPS) in RBCs cryopreservation. The results demonstrated that the addition of TAPS achieved a post-thaw recovery of RBCs at 79.12 ± 0.67%, accompanied by excellent biocompatibility (above 97%). Subsequently, the mechanism for preventing RBCs from cryopreservation injury was elucidated. On one hand, TAPS exhibits a significant amount of bound water and effectively inhibits ice recrystallization, thereby reducing mechanical damage. On the other hand, TAPS demonstrates high capacity to scavenge reactive oxygen species and strong endogenous antioxidant enzyme activity, providing effective protection against oxidative damage. Above all, TAPS can be readily removed through direct washing, and the RBCs after washing showed no significant differences in various physiological parameters (SEM, RBC hemolysis, ESR, ATPase activity, and Hb content) compared to fresh RBCs. Finally, the presented mathematical modeling analysis indicates the good benefits of TAPS. In summary, TAPS holds potential for both research and practical in the field of cryobiology, offering innovative insights for the improvement of RBCs cryopreservation in transfusion medicine.

Spatial ecology and microhabitat selection of the nocturnal pitviper Viridovipera stejnegeri (Squamata: Viperidae) in relation to prey.

Habitat is fundamental for facilitating various life activities in animals, for instance, snakes procure essential energy for survival and reproduction by selecting ambush microhabitats. While there has been extensive research on the selection of microhabitat for feeding in terrestrial and aquatic snakes, little is known about arboreal snakes. In the present study, we analyzed the ambush microhabitat preferences of Viridovipera stejnegeri, a widely distributed Asian pitviper in China, conducted association analysis between snake microhabitat and prey microhabitat and abundance to determine the ro5le of microhabitat selection in feeding. Employing random forest analysis and habitat selection functions, we further constructed a predictive framework for assessing the probability of ambush site selection by V. stejnegeri. Our results revealed that V. stejnegeri exhibited a distinct microhabitat preference for ambush prey. Among the 13 environmental factors assessed, V. stejnegeri showed pronounced preferences towards 12 of these factors, including climatic factors, geographical factors, and vegetation factors. Furthermore, although the preferences of V. stejnegeri overlapped substantially with those of its prey across multiple habitat factors, food abundance shows no significant association with various habitat factors of V. stejnegeri, and does not have significant predictive effect on habitat selection of V. stejnegeri. Therefore, we infer that V. stejnegeri does not preferentially select microhabitats with the highest food abundance, which does not support the hypothesis that "snakes select habitats based on the spatial distribution of prey abundance." By analyzing the characteristics of vegetation, geography, and climate, we conclude that V. stejnegeri tends to choose microhabitats with better ambush conditions to increase attack success rate, thereby achieving the optimal feeding success rate at the microhabitat scale, which is in line with the predictions of optimal foraging theory. This study provides new insights into the predation ecology and habitat selection of snakes.

Advancements and prospects of lipid-based nanoparticles: dual frontiers in cancer treatment and vaccine development.

Cancer is a complex heterogeneous disease that poses a significant public health challenge. In recent years, lipid-based nanoparticles (LBNPs) have expanded drug delivery and vaccine development options owing to their adaptable, non-toxic, tuneable physicochemical properties, versatile surface functionalisation, and biocompatibility. LBNPs are tiny artificial structures composed of lipid-like materials that can be engineered to encapsulate and deliver therapeutic agents with pinpoint accuracy. They have been widely explored in oncology; however, our understanding of their pharmacological mechanisms, effects of their composition, charge, and size on cellular uptake, tumour penetration, and how they can be utilised to develop cancer vaccines is still limited. Hence, we reviewed LBNPs' unique characteristics, biochemical features, and tumour-targeting mechanisms. Furthermore, we examined their ability to enhance cancer therapies and their potential contribution in developing anticancer vaccines. We critically analysed their advantages and challenges impeding swift advancements in oncology and highlighted promising avenues for future research.

LBNPs are tiny artificial particles made of lipids using different formulation methods. They are powerful and versatile delivery platforms with great potential as anticancer therapies. LBNPs have been tested in clinical applications and can safely deliver anticancer agents, including vaccine payloads designed to target various cancer types.LBNPs' size, surface charge, and targeting ligands can be modified during formulation, and they can be administered to specific tissues via various routes. LBNPs can target tumours and release their payload via active, passive, or stimuli-responsive mechanisms.Active targeting requires surface modification in order to target and deliver their payload, while passive targeting do not. Stimuli-responsive release mechanisms move to the tumour microenvironment and release their payload upon an internal or external stimulus.There are several challenges faced by LBNPs in delivering cancer drugs and vaccines, but advanced research methods have opened new doors vital for expanding their applications in clinical oncology.LBNPs offer the advantage of enhanced drug stability and bioavailability, prolonged circulation time of therapeutic agents in the bloodstream, and improved efficacy in targeting cancerous tissues.

Inulin Can Improve Red Blood Cell Cryopreservation by Promoting Vitrification, Stabilizing Cell Membranes, and Inhibiting Ice Recrystallization.

In transfusion medicine, the cryopreservation of red blood cells (RBCs) is of major importance. The organic solvent glycerol (Gly) is considered the current gold-standard cryoprotectant (CPA) for RBC cryopreservation, but the deglycerolization procedure is complex and time-consuming, resulting in severe hemolysis. Therefore, it remains a research hotspot to find biocompatible and effective novel CPAs. Herein, the natural and biocompatible inulin, a polysaccharide, was first employed as a CPA for RBC cryopreservation. The presence of inulin could improve the thawed RBC recovery from 11.83 ± 1.40 to 81.86 ± 0.37%. It was found that inulin could promote vitrification because of its relatively high viscosity and glass transition temperature (Tg'), thus reducing the damage during cryopreservation. Inulin possessed membrane stability, which also had beneficial effects on RBC recovery. Moreover, inulin could inhibit the mechanical damage induced by ice recrystallization during thawing. After cryopreservation, the RBC properties were maintained normally. Mathematical modeling analysis was adopted to compare the performance of inulin, Gly, and hydroxyethyl starch (HES) in cryopreservation, and inulin presented the best efficiency. This work provides a promising CPA for RBC cryopreservation and may be beneficial for transfusion therapy in the clinic.

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.

The obesogenic side of Genistein.

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpß), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.

A tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform for triple-enhanced chemodynamic therapy combined with chemotherapy and H2S therapy.

The high glutathione (GSH) concentration and insufficient H2O2 content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, H2S generation, self-supplied H2O2, co-delivery of doxorubicin (DOX) and Fenton reagent Fe2+ is presented for synergistic triple-enhanced CDT/chemotherapy/H2S therapy. Because the tetrasulfide bond is sensitive to GSH, the nanoplatform can effectively consume GSH, leading to ROS accumulation and H2S generation in the GSH-overexpressed tumor microenvironment. Meanwhile, tetrasulfide bond-induced GSH-depletion triggers the degradation of nanoparticles and the release of DOX and Fe2+. Immediately, Fe2+ catalyzes endogenous H2O2 to highly toxic hydroxyl radicals (˙OH) for CDT, and H2S induces mitochondria injury and causes energy deficiency. Of note, H2S can also decrease the decomposition of H2O2 to augment CDT by downregulating catalase. DOX elicits chemotherapy and promotes H2O2 production to provide a sufficient substrate for enhanced CDT. Importantly, the GSH depletion significantly weakens the scavenging effect on the produced ˙OH, guaranteeing the enhanced and highly efficient CDT. Based on the synergistic effect of triple-augmented CDT, H2S therapy and DOX-mediated chemotherapy, the treatment with this nanoplatform gives rise to a superior antitumor outcome.

Cryopreservation of bioflavonoid-rich plant sources and bioflavonoid-microcapsules: emerging technologies for preserving bioactivity and enhancing nutraceutical applications.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

Inhibitory effect of cyclodextrin on Maillard reaction and its mechanism.

Maillard reaction in pharmaceutical preparations refers to a complex chemical reaction existing between reducing excipients and amino-containing drugs in preparations, which can cause a series of quality problems in preparations. Maillard reaction belongs to chemical incompatibility in preparations, and measures should be taken to reduce or avoid it. In this study, the effect of cyclodextrins (commonly used pharmaceutical excipients) on the Maillard reaction and its mechanism in the lysine hydrochloride-lactose solid preparation model were explored for the first time. Our research results show that the embedding of lysine in cyclodextrin can inhibit the Maillard reaction of lysine to some extent, and the embedding of lysine in cyclodextrin with different structures has differences in the inhibitory effects on Maillard reaction.Among the five cyclodextrins we studied, α-CD and HP-ß-CD embedded lysine can reduce Maillard reaction to a greater extent. We suspect that this may be related to the stability of the embedded substance, which needs further study and verification. And our research shows that the inclusion complex between lysine and cyclodextrin may be the result of hydrogen bond, electrostatic attraction, hydrophobic interaction and van der Waals force. Cyclodextrin is expected to solve the problem of Maillard reaction in pharmaceutical industry to some extent.

Starting Editorial of "Cellular Damage: Protection and Induction" Addressing Hot Topics in Cellular Damage, Protection of Cells and Therapy Targeting Bad Cells.

The cell, the fundamental unit of life, is constantly subjected to a myriad of molecular biophysical disturbances [...].

A cooperation tale of biomolecules and nanomaterials in nanoscale chiral sensing and separation.

The cooperative relationship between biomolecules and nanomaterials makes up a beautiful tale about nanoscale chiral sensing and separation. Biomolecules are considered a fabulous chirality 'donor' to develop chiral sensors and separation systems. Nature has endowed biomolecules with mysterious chirality. Various nanomaterials with specific physicochemical attributes can realize the transmission and amplification of this chirality. We focus on highlighting the advantages of combining biomolecules and nanomaterials in nanoscale chirality. To enhance the sensors' detection sensitivity, novel cooperation approaches between nanomaterials and biomolecules have attracted tremendous attention. Moreover, innovative biomolecule-based nanocomposites possess great importance in developing chiral separation systems with improved assay performance. This review describes the formation of a network based on nanomaterials and biomolecules mainly including DNA, proteins, peptides, amino acids, and polysaccharides. We hope this tale will record the perpetual relation between biomolecules and nanomaterials in nanoscale chirality.

Biophysics in Membrane of Cells.

The membrane of a cell, often compared to a dynamic city border, carries out an intricate dance of controlling entry and exit, guarding the valuable life processes occurring inside [...].

Smart design of a therapeutic nanoplatform for mitochondria-targeted copper-depletion therapy combined with chemotherapy.

Mitochondria-targeted copper-depletion is emerging as an attractive strategy to combat cancer. However, existing copper molecular chelators are non-specific, toxic and ineffective. Here, it is reported that multifunctional nanoparticles (MSN-TPP/BNA-DPA) can not only target mitochondria to deprive copper ions to trigger copper-depletion therapy, but also serve as nanocarriers to deliver anticancer drugs for chemotherapy, which are engineered by conjugating a fluorophore 4-bromo-1,8-naphthalicanhydride (BNA), a copper-depriving moiety dimethylpyridinamine (DPA) and a mitochondrial targeting ligand triphenylphosphonium (TPP) on the surface of mesoporous silica nanoparticles (MSN). BNA and the internal charge transfer of compound BNA-DPA endow MSN-TPP/BNA-DPA with green fluorescence emission upon UV excitation, which can be used to monitor the cellular uptake of nanoparticles. When copper ions bind to DPA, green fluorescence is quenched, providing visualization feedback of copper-depletion. Therapeutically, mitochondria-targeted copper-depletion effectively causes mitochondria damage, elevated oxidative stress and reduced ATP production to induce intensive cancer cell death. Moreover, the mesoporous structure enables MSN-TPP/BNA-DPA to deliver doxorubicin to mitochondria for chemotherapy and enhances copper-depletion therapy through H2O2 production. Together, the synergistic therapeutic effect of enhanced copper-depletion therapy and doxorubicin-mediated chemotherapy achieves a remarkable cancer cell-killing effect and significant tumor growth inhibition in 4T1 tumor-bearing mice. This work provides an efficacious strategy for copper-depletion based synergistic cancer therapy.

Construction of chiral capillary electrochromatography microsystems based on Aspergillus sp. CM96.

Novel chiral capillary electrochromatography (CEC) microsystems were constructed based on Aspergillus sp. CM96. As a newly discovered intrinsic characteristic of the cell, cell chirality occupies an essential position in life evolution. Aspergillus sp. CM96 spore (CM96s) was chosen as a proof of concept to develop chiral capillary columns. Interestingly, various types of amino acid (AA) enantiomers were baseline separated under the optimized conditions. Furthermore, the time-dependent chiral interactions between AAs and CM96s were explored in a wider space. Pectinases generated from Aspergillus sp. CM96 fermentation were immobilized onto graphene oxide-functionalized capillary silica monoliths for separating AA enantiomers. Molecular docking simulations were performed to explore chiral separation mechanisms of pectinase for AA enantiomers. These results indicated that Aspergillus sp. CM96-based CEC microsystems have a significant advantage for chiral separation.

Enhancing bioavailability of natural extracts for nutritional applications through dry powder inhalers (DPI) spray drying: technological advancements and future directions.

Natural ingredients have many applications in modern medicine and pharmaceutical projects. However, they often have low solubility, poor chemical stability, and low bioavailability in vivo. Spray drying technology can overcome these challenges by enhancing the properties of natural ingredients. Moreover, drug delivery systems can be flexibly designed to optimize the performance of natural ingredients. Among the various drug delivery systems, dry powder inhalation (DPI) has attracted much attention in pharmaceutical research. Therefore, this review will focus on the spray drying of natural ingredients for DPI and discuss their synthesis and application.

Cryopreservation of tissues and organs: present, bottlenecks, and future.

Tissue and organ transplantation continues to be an effective measure for saving the lives of certain critically ill patients. The organ preservation methods that are commonly utilized in clinical practice are presently only capable of achieving short-term storage, which is insufficient for meeting the demand for organ transplantation. Ultra-low temperature storage techniques have garnered significant attention due to their capacity for achieving long-term, high-quality preservation of tissues and organs. However, the experience of cryopreserving cells cannot be readily extrapolated to the cryopreservation of complex tissues and organs, and the latter still confronts numerous challenges in its clinical application. This article summarizes the current research progress in the cryogenic preservation of tissues and organs, discusses the limitations of existing studies and the main obstacles facing the cryopreservation of complex tissues and organs, and finally introduces potential directions for future research efforts.