MLL-AF9 regulates transcriptional initiation in mixed lineage leukemic cells.

Mixed lineage leukemia-fusion proteins (MLL-FPs) are believed to maintain gene activation and induce MLL through aberrantly stimulating transcriptional elongation, but the underlying mechanisms are incompletely understood. Here, we show that both MLL1 and AF9, one of the major fusion partners of MLL1, mainly occupy promoters and distal intergenic regions, exhibiting chromatin occupancy patterns resembling that of RNA polymerase II in HEL, a human erythroleukemia cell line without MLL1 rearrangement. MLL1 and AF9 only coregulate over a dozen genes despite of their co-occupancy on thousands of genes. They do not interact with each other, and their chromatin occupancy is also independent of each other. Moreover, AF9 deficiency in HEL cells decreases global TBP occupancy while decreases CDK9 occupancy on a small number of genes, suggesting an accessory role of AF9 in CDK9 recruitment and a possible major role in transcriptional initiation via initiation factor recruitment. Importantly, MLL1 and MLL-AF9 occupy promoters and distal intergenic regions, exhibiting identical chromatin occupancy patterns in MLL cells, and MLL-AF9 deficiency decreased occupancy of TBP and TFIIE on major target genes of MLL-AF9 in iMA9, a murine acute myeloid leukemia cell line inducibly expressing MLL-AF9, suggesting that it can also regulate initiation. These results suggest that there is no difference between MLL1 and MLL-AF9 with respect to location and size of occupancy sites, contrary to what people have believed, and that MLL-AF9 may also regulate transcriptional initiation in addition to widely believed elongation.

Downregulation of Splicing Factor PTBP1 Curtails FBXO5 Expression to Promote Cellular Senescence in Lung Adenocarcinoma.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and post-transcriptional regulation. Moreover, PTBP1 has been implicated as a causal factor in tumorigenesis. However, the involvement of PTBP1 in cellular senescence, a key biological process in aging and cancer suppression, remains to be clarified. Here, it is shown that PTBP1 is associated with the facilitation of tumor growth and the prognosis in lung adenocarcinoma (LUAD). PTBP1 exhibited significantly increased expression in various cancer types including LUAD and showed consistently decreased expression in multiple cellular senescence models. Suppression of PTBP1 induced cellular senescence in LUAD cells. In terms of molecular mechanisms, the silencing of PTBP1 enhanced the skipping of exon 3 in F-box protein 5 (FBXO5), resulting in the generation of a less stable RNA splice variant, FBXO5-S, which subsequently reduces the overall FBXO5 expression. Additionally, downregulation of FBXO5 was found to induce senescence in LUAD. Collectively, these findings illustrate that PTBP1 possesses an oncogenic function in LUAD through inhibiting senescence, and that targeting aberrant splicing mediated by PTBP1 has therapeutic potential in cancer treatment.

Real-time monitoring of glucose metabolism and effects of metformin on HepG2 cells using 13C in-cell NMR spectroscopy.

Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13C in-cell NMR spectroscopy. Metabolic tracing with U-13C6-glucose revealed that metformin significantly increased the production of 13C-G3P and 13C-glycerol, which were reported to attenuate liver cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13C-lactate, 13C-alanine, 13C-glycine, and 13C-glutamate. Moreover, the expression levels of enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine.

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Total Synthesis of Quebrachamine and Kopsiyunnanine D.

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

Injectable Self-Healing Antibacterial Hydrogels with Tailored Functions by Loading Peptide Nanofiber-Biomimetic Silver Nanoparticles.

Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.

Gold Nanoparticles-Modified 2D Self-Assembled Amphiphilic Peptide Nanosheets with High Biocompatibility and Photothermal Therapy Efficiency.

Amphiphilic peptides have garnered significant attention due to their highly designable and self-assembling behaviors. Self-assembled peptides hold excellent potential in various fields such as biosensing, environmental monitoring, and drug delivery, owing to their remarkable biological, physical, and chemical properties. While nanomaterials formed by peptide self-assembly have found widespread use in biomedical applications, the development of 2D peptide nanosheets based on the self-assembly of amphiphilic peptides remains challenging in terms of rational design and morphology modulation. In this study, rationally designed amphiphilic peptide molecules are self-assembled into peptide nanosheets (PNS) under specific conditions to encapsulate gold nanoparticles (AuNPs), resulting in the formation of AuNPs/PNS hybrid materials with high photothermal conversion efficiency. The findings demonstrate that 2D PNS enhances the overall photothermal therapy effect of the nanohybrid materials due to their larger hosting area for AuNPs and higher biocompatibility. The well-designed amphiphilic peptides in this study offer insights into the structural design and functional modulation of self-assembled molecules. In addition, the constructed biomimetic-functional 2D inorganic/organic nanohybrid materials hold potential applications in biomedical engineering.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres.

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Single-cell RNA-seq analysis decodes the kidney microenvironment induced by polystyrene microplastics in mice receiving a high-fat diet.

In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8+ effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4+ macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4+ macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4+ macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals.

Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.

Genetic Analysis of the Emerging Citrus Yellow Vein Clearing Virus Reveals a Divergent Virus Population in American Isolates.

Citrus yellow vein clearing virus is a previously reported citrus virus from Asia with widespread distribution in China. In 2022, the California Department of Food and Agriculture conducted a multipest citrus survey targeting multiple citrus pathogens including citrus yellow vein clearing virus (CYVCV). In March 2022, a lemon tree with symptoms of vein clearing, chlorosis, and mottling in a private garden in the city of Tulare, California, tested positive for CYVCV, which triggered an intensive survey in the surrounding areas. A total of 3,019 plant samples, including citrus and noncitrus species, were collected and tested for CYVCV using conventional reverse transcription polymerase chain reaction, reverse transcription quantitative polymerase chain reaction, and Sanger sequencing. Five hundred eighty-six citrus trees tested positive for CYVCV, including eight citrus species not previously recorded infected under field conditions. Comparative genomic studies were conducted using 17 complete viral genomes. Sequence analysis revealed two major phylogenetic groups. Known Asian isolates and five California isolates from this study made up the first group, whereas all other CYVCV isolates from California formed a second group, distinct from all worldwide isolates. Overall, the CYVCV population shows rapid expansion and high differentiation indicating a population bottleneck typical of a recent introduction into a new geographic area.

Integrated metabolomic and transcriptomic analysis reveals variation in the metabolites of Dendrobium officinale, Dendrobium huoshanense, Dendrobium nobile.

INTRODUCTION: Dendrobium is a perennial herb of the genus Dendrobium in the orchid family. Generally, Dendrobium officinale (TP) and Dendrobium huoshanense (HS) are both considered to have the function of yin-nourishing, while Dendrobium nobile (JC) has better efficacy of heat-clearing. However, because of the wide variety of Dendrobium species, the classification and clinical application of Dendrobium are often confused clearly distinguished in different medicinal uses. OBJECTIVE: In order to compare the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) of the three Dendrobium. METHODS: We selected TP, HS, and JC cultivated on stone for metabolomic and transcriptomic analyses between 2 and 3 years. RESULTS: The results showed that a total of 489 metabolites were obtained, including 72 were DAMs. The 72 DAMs were mainly enriched in metabolic pathways and biosynthesis of secondary metabolites. Transcriptome analysis results showed that 1,038 annotated DEGs were identified among the three Dendrobium species. The comprehensive analysis showed that the three Dendrobium differed in the distribution of the content of four major active components: flavonoids, amino acids, alkaloids, and sugars and alcohols, among which the DAMs and DEGs were mainly enriched in metabolic pathways and secondary metabolite biosynthesis. CONCLUSION: In this study, metabolomics and transcriptomics were utilized to compare the differences among the three species of Dendrobium, to provide theoretical references for future research and selection of different species of Dendrobium based on different medicinal uses, and to lay the foundation for further research on the biosynthesis of flavonoids in Dendrobium.

Facile Synthesis of Fe-Doped, Algae Residue-Derived Carbon Aerogels for Electrochemical Dopamine Biosensors.

An abnormal level of dopamine (DA), a kind of neurotransmitter, correlates with a series of diseases, including Parkinson's disease, Willis-Ekbom disease, attention deficit hyperactivity disorder, and schizophrenia. Hence, it is imperative to achieve a precise, rapid detection method in clinical medicine. In this study, we synthesized nanocomposite carbon aerogels (CAs) doped with iron and iron carbide, based on algae residue-derived biomass materials, using Fe(NO3)3 as the iron source. The modified glassy carbon electrode (GCE) for DA detection, denoted as CAs-Fe/GCE, was prepared through surface modification with this composite material. X-ray photoelectron spectroscopy and X-ray diffraction characterization confirmed the successful doping of iron into the as-prepared CAs. Additionally, the electrochemical behavior of DA on the modified electrode surface was investigated and the results demonstrate that the addition of the CAs-Fe promoted the electron transfer rate, thereby enhancing their sensing performance. The fabricated electrochemical DA biosensor exhibits an accurate detection of DA in the concentration within the range of 0.01~200 µM, with a detection limit of 0.0033 µM. Furthermore, the proposed biosensor is validated in real samples, showing its high applicability for the detection of DA in beverages.

[Effect and mechanism of EtOAc extract of Draconis Sanguis onimproving atherosclerosis in ApoE~(-/-) mice].

This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells.

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 µM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.

Ti3C2 Nanosheets Functionalized with Ferritin-Biomimetic Platinum Nanoparticles for Electrochemical Biosensors of Nitrite.

Nitrites widely exist in human life and the natural environment, but excessive contents of nitrites will result in adverse effects on the environment and human health; hence, sensitive and stable nitrite detection systems are needed. In this study, we report the synthesis of Ti3C2 nanosheets functionalized with apoferritin (ApoF)-biomimetic platinum (Pt) nanoparticle (Pt@ApoF/Ti3C2) composite materials, which were formed by using ApoF as a template and protein-inspired biomineralization. The formed nanohybrid exhibits excellent electrochemical sensing performance towards nitrite (NaNO2). Specifically, the Pt@ApoF catalyzes the conversion of nitrites into nitrates, converting the chemical signal into an electrical signal. The prepared Pt@ApoF/Ti3C2-based electrochemical NaNO2 biosensors demonstrate a wide detection range of 0.001-9 mM with a low detection limit of 0.425 µM. Additionally, the biosensors possess high selectivity and sensitivity while maintaining a relatively stable electrochemical sensing performance within 7 days, enabling the monitoring of NaNO2 in complex environments. The successful preparation of the Pt@ApoF/Ti3C2 nanohybrid materials provides a new approach for constructing efficient electrochemical biosensors, offering a simple and rapid method for detecting NaNO2 in complex environments.

Material basis and core chemical structure of Dendrobium officinale polysaccharides against colitis-associated cancer based on anti-inflammatory activity.

It has been claimed that Dendrobium officinale polysaccharides (PSs) can degrade into oligosaccharide and then transform into short-chain fatty acids in the intestine after oral administration, and play an anti-colitis-associated cancer (CAC) effect by inhibiting intestinal inflammation. However, the material basis and core chemical structure underlying the anti-colon cancer properties of PSs have not yet been elucidated. In this study, PSs were degraded into enzymatic oligosaccharides (OSs) using ß-mannanase. The results of in vivo experiments revealed that PSs and OSs administered by gastric lavage had similar antitumor effects in CAC mice. OS-1 (Oligosaccharide compounds 1) and OS-2 (Oligosaccharide compounds 2) were further purified and characterized from OSs, and it was found that OS-1, OS-2, OSs, and PSs had similar and consistent anti-inflammatory activities in vitro. Chemical structure comparison and evaluation revealed that the chemical structure of ß-D-Manp-(1 â†’ 4)-ß-D-Glcp corresponding to OS-1 was the least common PS structure with anti-colitic activity. Therefore, our findings suggest that OSs are the material basis for PSs to exert anti-CAC activity and that the chemical structure of ß-D-Manp-(1 â†’ 4)-ß-D-Glcp corresponding to OS-1 is the core chemical structure of PSs against CAC.

Recent advances in nanocrystal-based technologies applied for ocular drug delivery.

INTRODUCTION: The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs. AREAS COVERED: This article focuses on the ophthalmic nanocrystal technologies and products that are in the literature, clinical trials, and even on the market. The recent research progress in the preparation, ocular application, and absorption of nanocrystals are highlighted, and the pros and cons of nanocrystals in overcoming the physiological barriers of the eye are also summarized. EXPERT OPINION: Nanocrystals have demonstrated success as glucocorticoid eye drops in the treatment of anterior segment diseases. However, the thermodynamic stability of nanocrystals remains the major challenge in product development. New technologies for efficiently optimizing stabilizers and sterilization processes are still expected. Strategies to confer more diverse functions via surface modification are also worth exploration to improve the potential of nanocrystals in delivering poorly water-soluble drugs to posterior segment of the eye.

Recent Advances in Metal-Organic Framework (MOF)-Based Composites for Organic Effluent Remediation.

Environmental pollution caused by organic effluents emitted by industry has become a worldwide issue and poses a serious threat to the public and the ecosystem. Metal-organic frameworks (MOFs), comprising metal-containing clusters and organic bridging ligands, are porous and crystalline materials, possessing fascinating shape and size-dependent properties such as high surface area, abundant active sites, well-defined crystal morphologies, and huge potential for surface functionalization. To date, numerous well designated MOFs have emerged as critical functional materials to solve the growing challenges associated with water environmental issues. Here we present the recent progress of MOF-based materials and their applications in the treatment of organic effluents. Firstly, several traditional and emerging synthesis strategies for MOF composites are introduced. Then, the structural and functional regulations of MOF composites are presented and analyzed. Finally, typical applications of MOF-based materials in treating organic effluents, including chemical, pharmaceutical, textile, and agricultural wastewaters are summarized. Overall, this review is anticipated to tailor design and regulation of MOF-based functional materials for boosting the performance of organic effluent remediation.

Description of a new Asian Leaf Litter Toad of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) from southern Guizhou Province, China.

Background: The Asian leaf litter toads of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) inhabit the forest floor and rocky streams in hilly evergreen forests and are widely distributed from southern China, west to north-eastern India and Myanmar, through mainland Indochina to Peninsular Malaysia and the Island of Borneo. New information: A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.