Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Theoretical study of protein adsorption on graphene/h-BN heterostructures.

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.

Adaptability of melanocytes post ultraviolet stimulation in patients with melasma.

BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.

The quantitative analysis of low-concentration (2%) ALA-PDT assisted with Q-switch 1064-nm Nd:YAG laser for acne vulgaris treatment.

Conventional 5-aminolevulinic acid-photodynamic (ALA-PDT) therapy (10-20%) has been widely applied for moderate-to-severe acne. The aim of this study is to investigate the effects of non-ablative Q-switched 1064-nm Nd:YAG laser-assisted ALA-PDT with low concentration (2%) on the treatment of acne vulgaris. Enrolled patients were randomly assigned to 2 groups. One group received combined therapy of 2% ALA-PDT and non-ablative Q-switched 1064-nm Nd:YAG laser, and the other received only 2% ALA-PDT. Patients in each group had received 3-session treatments with 4-week intervals (week 0, 4, and 8). Sebum secretion, melanin index, erythema index, and transepidermal water loss (TEWL) were assessed at week 2, 8, 12, and 24. VISIA® skin image system score and global esthetic improvement scale (GAIS) were also evaluated. Twenty-four participants were enrolled and evenly randomized to two groups. Significant improvement in sebum secretion was noted in combined therapy group compared to the monotherapy group at week 12 (37.5% versus 16.3%), and the improvement would still be noted until week 24 (18.3% versus 17.4%). Combined group also showed more severe melanin index and erythema index after treatment. For VISIA® skin analysis, patients in combined group had better percentile ranking in porphyrins and red-light images. There were no significant differences in GAIS at the end of the follow-up between each group, whereas higher proportion of satisfaction was noted in combined group at week 2. With the assistance of laser, low concentrations (2%) of 5-ALA can provide effective phototoxic reactions in treating acne vulgaris. The satisfaction of patients is high with acceptable adverse effects.

Molecular understanding of charge effect on desalination performance in lamellar MoS2 membranes.

Due to its advantages of superior oxidation resistance, excellent chemical stability and non-toxicity, molybdenum disulfide (MoS2) has shown prospects in seawater desalination applications. In this manuscript, molecular dynamics (MD) simulation has been employed to explore the effect of charge distribution in MoS2 nanosheets on the desalination performance of the lamellar MoS2 membrane. It is found that the model considering the atomic charge better describes the transport behavior of salt solution in the membranes. The water flux passing through the lamellar MoS2 membrane would be influenced little by the atomic charges in the MoS2 nanosheet. The lamellar MoS2 membrane considering the atomic charge distribution shows a screening effect between Na+ and Cl- ions.

Photoaging and Sequential Function Reversal with Cellular-Resolution Optical Coherence Tomography in a Nude Mice Model.

Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo®, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had >60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions.

Fermented Taiwanofungus camphoratus Extract Ameliorates Psoriasis-Associated Response in HaCaT Cells via Modulating NF-𝜠B and mTOR Pathways.

Psoriasis is a chronic autoimmune disease, and until now, it remains an incurable disease. Therefore, the development of new drugs or agents that ameliorate the disease will have marketing potential. Taiwanofungus camphoratus (TC) is a specific fungus in Taiwan. It is demonstrated to have anticancer, anti-inflammation, and hepatoprotective effects. However, the effects of TC fermented extract on psoriasis are under investigation. In this research, we studied the ability of TC on antioxidative activity and the efficacy of TC on interleukin-17 (IL-17A)-induced intracellular oxidative stress, inflammation-relative, and proliferation-relative protein expression in human keratinocytes. The results of a DPPH radical scavenging assay, reducing power assay, and hydroxyl peroxide inhibition assay indicated that TC has a potent antioxidant ability. Furthermore, TC could reduce IL-17A-induced intracellular ROS generation and restore the NADPH level. In the investigation of pathogenesis, we discovered TC could regulate inflammatory and cell proliferation pathways via p-IKKα/p-p65 and p-mTOR/p-p70S6k signaling pathways in human keratinocytes. In conclusion, TC showed characteristics such as antioxidant, anti-inflammatory, and anti-psoriatic-associated responses. It is expected to be developed as a candidate for oxidative-stress-induced skin disorders or psoriasis treatment.

Atomistic insights into the separation mechanism of multilayer graphene membranes for water desalination.

Graphene-based membranes have been extensively explored owing to their excellent separation properties. In this paper, multiple factors regarding desalination performance were investigated by molecular dynamics (MD) simulations. These factors include the interlayer spacing distance (H), the gap width (dG), offset (O), and the number of gaps and layers in a multilayer graphene membrane (MGM). It is found that salt rejection is influenced significantly by the interlayer spacing distance owing to the largest free energy between ions and graphene sheets as well as the relatively larger size of the hydration layer around the ions. The optimal desalting parameter (dG = 1 nm, H = 0.8 nm) was selected; MGM systems based on the optimized parameter exhibited excellent salt rejection for NaCl, MgCl2 and CaCl2 solutions. These results can provide some ideas for the future design of graphene-based membranes.

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.

Theoretical studies on key factors in DNA sequencing using atomically thin molybdenum disulfide nanopores.

Nanopore-based DNA sequencing is considered to be a low-cost, high resolution and superfast method. Solid state nanopores, especially MoS2 nanopores, have been considered to be a promising choice for DNA sequencing. However, researchers still have a very limited understanding of the effects of multiple factors on MoS2-based DNA sequencing. In this study, the effects of the applied voltage and the diameter of the MoS2 nanopore on the resolution of DNA sequencing were investigated. Our results demonstrate that the translocation time of DNA can increase with a decrease in the applied voltage. DNA can be stretched significantly to translocate a 2 nm nanopore under a high applied voltage (>400 mV nm-1). To achieve a 1 base per µs translocation speed (1 GHz bandwidth), we suggest that three methods could be applied, including a decrease in the applied voltage, a decrease in the diameter of the MoS2 nanopore or modification of the MoS2 nanopore. In addition, the size of the nanopore can severely affect the possibility of DNA entering the nanopore, and the translocation time of DNA could be significantly increased with a smaller MoS2 nanopore. These findings may help to design MoS2 nanopores with higher resolution for use in DNA sequencing.

Adsorption Behavior and Mechanism of SCA-1 on a Calcite Surface: A Molecular Dynamics Study.

The crystallization mechanism for natural mineral, especially the role of biological molecules in biomineralization, is still under debate. Protein adsorption on material surfaces plays a key role in biomineralization. In this article, molecular dynamics (MD) simulations were performed to systematically investigate the adsorption behavior of struthio camelus eggshell protein struthiocalcin-1 (SCA-1) on the calcite (104) surface with several different starting orientations in an explicit water environment. For each binding configuration, detailed adsorption behaviors and a mechanism were presented with the analysis of interaction energy, binding residues, hydrogen bonding, and structures (such as DSSP, dipole moment, and the electrostatic potential calculation). The results indicate that the positively charged and polar residues are the dominant residues for protein adsorption on the calcite (104) surface, and the strong electrostatic interaction drives the binding of model protein to the surface. The hydrogen bond bridge was found to play an important role in surface interactions as well. These results also demonstrate that SCA-1 is relatively rigid in spite of strong adsorption with few structural changes in α-helix and ß-sheet contents. The results of the orientation calculation suggest that the dipole moment of the protein tends to remain parallel to calcite in most stable cases, which was confirmed by electrostatic potential isosurfaces analysis.

Computer simulation of water desalination through boron nitride nanotubes.

Development of high-efficiency and low-cost seawater desalination technologies is critical to solving the global water crisis. Herein we report a fast water filtering method with high salt rejection by boron nitride nanotubes (BNNTs). The effect of the radius of BNNTs on water filtering and salt rejection was investigated by molecular dynamics (MD) simulation. Our simulation results demonstrate that fast water permeation and high salt rejection could be achieved by BNNT(7,7) under both high pressure and low pressure. The potential of mean force (PMF) of Na+ ion and water molecule through BNNT(7,7) further revealed the mechanism of seawater desalination by BNNT(7,7). Using BNNT(7,7) array, a 10 cm2 nanotube membrane with 1.5 × 1013 pores per cm2 will produce freshwater with a flow rate of 98 L per day per MPa under 100 MPa. Our study shows the potential application of BNNTs membrane for fast and efficient desalination.

Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study.

BACKGROUND: Gout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case-control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese. METHODS: A total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis. RESULTS: No deviation from the Hardy-Weinberg equilibrium was observed either in the case or control cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p = 1.78E(-4), OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E(-7), OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p = 3.94E(-5); rs1183201 in SLC17A1, corrected p = 0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with rs780094 (located in GCKR, corrected p = 2.96E(-4)). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p = 0.143). CONCLUSIONS: Three SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.

The genetic basis of population fecundity prediction across multiple field populations of Nilaparvata lugens.

Identifying the molecular markers for complex quantitative traits in natural populations promises to provide novel insight into genetic mechanisms of adaptation and to aid in forecasting population dynamics. In this study, we investigated single nucleotide polymorphisms (SNPs) using candidate gene approach from high- and low-fecundity populations of the brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) divergently selected for fecundity. We also tested whether the population fecundity can be predicted by a few SNPs. Seven genes (ACE, fizzy, HMGCR, LpR, Sxl, Vg and VgR) were inspected for SNPs in N. lugens, which is a serious insect pest of rice. By direct sequencing of the complementary DNA and promoter sequences of these candidate genes, 1033 SNPs were discovered within high- and low-fecundity BPH populations. A panel of 121 candidate SNPs were selected and genotyped in 215 individuals from 2 laboratory populations (HFP and LFP) and 3 field populations (GZP, SGP and ZSP). Prior to association tests, population structure and linkage disequilibrium (LD) among the 3 field populations were analysed. The association results showed that 7 SNPs were significantly associated with population fecundity in BPH. These significant SNPs were used for constructing general liner models with stepwise regression. The best predictive model was composed of 2 SNPs (ACE-862 and VgR-816 ) with very good fitting degree. We found that 29% of the phenotypic variation in fecundity could be accounted for by only two markers. Using two laboratory populations and a complete independent field population, the predictive accuracy was 84.35-92.39%. The predictive model provides an efficient molecular method to predict BPH fecundity of field populations and provides novel insights for insect population management.

Understanding the structure of hydrophobic surfactants at the air/water interface from molecular level.

Understanding the behavior of fluorocarbon surfactants at the air/water interface is crucial for many applications, such as lubricants, paints, cosmetics, and fire-fighting foams. In this study, molecular dynamics (MD) simulations were employed to investigate the microscopic properties of non-ionic fluorocarbon surfactants at the air/water interface. Several properties, including the distribution of head groups, the distribution probability of the tilt angle between hydrophobic tails with respect to the xy plane, and the order parameter of surfactants, were computed to probe the structure of hydrophobic surfactants at the air/water interface. The effects of the monomer structure on interfacial phenomena of non-ionic surfactants were investigated as well. It is observed that the structure of fluorocarbon surfactants at the air/water interface is more ordered than that of hydrocarbons, which is dominated by the van der Waals interaction between surfactants and water molecules. However, replacing one or two CF2 with one or two CH2 group does not significantly influence the interfacial structure, suggesting that hydrocarbons may be promising alternatives to perfluorinated surfactants.

Nanomaterials-incorporated polymeric microneedles for wound healing applications.

There is a growing and urgent need for developing novel biomaterials and therapeutic approaches for efficient wound healing. Microneedles (MNs), which can penetrate necrotic tissues and biofilm barriers at the wound and deliver active ingredients to the deeper layers in a minimally invasive and painless manner, have stimulated the interests of many researchers in the wound-healing filed. Among various materials, polymeric MNs have received widespread attention due to their abundant material sources, simple and inexpensive manufacturing methods, excellent biocompatibility and adjustable mechanical strength. Meanwhile, due to the unique properties of nanomaterials, the incorporation of nanomaterials can further extend the application range of polymeric MNs to facilitate on-demand drug release and activate specific therapeutic effects in combination with other therapies. In this review, we firstly introduce the current status and challenges of wound healing, and then outline the advantages and classification of MNs. Next, we focus on the manufacturing methods of polymeric MNs and the different raw materials used for their production. Furthermore, we give a summary of polymeric MNs incorporated with several common nanomaterials for chronic wounds healing. Finally, we discuss the several challenges and future prospects of transdermal drug delivery systems using nanomaterials-based polymeric MNs in wound treatment application.

Porous silicon-based sensing and delivery platforms for wound management applications.

Wound management remains a great challenge for clinicians due to the complex physiological process of wound healing. Porous silicon (PSi) with controlled pore morphology, abundant surface chemistry, unique photonic properties, good biocompatibility, easy biodegradation and potential bioactivity represent an exciting class of materials for various biomedical applications. In this review, we focus on the recent progress of PSi in the design of advanced sensing and delivery systems for wound management applications. Firstly, we comprehensively introduce the common type, normal healing process, delaying factors and therapeutic drugs of wound healing. Subsequently, the typical fabrication, functionalization and key characteristics of PSi have been summarized because they provide the basis for further use as biosensing and delivery materials in wound management. Depending on these properties, the rise of PSi materials is evidenced by the examples in literature in recent years, which has emphasized the robust potential of PSi for wound monitoring, treatment and theranostics. Finally, challenges and opportunities for the future development of PSi-based sensors and delivery systems for wound management applications are proposed and summarized. We hope that this review will help readers to better understand current achievements and future prospects on PSi-based sensing and delivery systems for advanced wound management.

CaCO3 nanoplatform for cancer treatment: drug delivery and combination therapy.

The use of nanocarriers for drug delivery has opened up exciting new possibilities in cancer treatment. Among them, calcium carbonate (CaCO3) nanocarriers have emerged as a promising platform due to their exceptional biocompatibility, biosafety, cost-effectiveness, wide availability, and pH-responsiveness. These nanocarriers can efficiently encapsulate a variety of small-molecule drugs, proteins, and nucleic acids, as well as co-encapsulate multiple drugs, providing targeted and sustained drug release with minimal side effects. However, the effectiveness of single-drug therapy using CaCO3 nanocarriers is limited by factors such as multidrug resistance, tumor metastasis, and recurrence. Combination therapy, which integrates multiple treatment modalities, offers a promising approach for tackling these challenges by enhancing efficacy, leveraging synergistic effects, optimizing therapy utilization, tailoring treatment approaches, reducing drug resistance, and minimizing side effects. CaCO3 nanocarriers can be employed for combination therapy by integrating drug therapy with photodynamic therapy, photothermal therapy, sonodynamic therapy, immunotherapy, radiation therapy, radiofrequency ablation therapy, and imaging. This review provides an overview of recent advancements in CaCO3 nanocarriers for drug delivery and combination therapy in cancer treatment over the past five years. Furthermore, insightful perspectives on future research directions and development of CaCO3 nanoparticles as nanocarriers in cancer treatment are discussed.