Progress in the Application of Microneedles in Eye Disorders and the Proposal of the Upgraded Microneedle with Spinule.

PURPOSE: In the local administration methods for treating eye diseases, the application of microneedles has great potential due to the shortcomings of low efficacy and significant side effects of local administration preparations. This article provides ideas for the research on the application of ophthalmic microneedle in the treatment of eye diseases. RESULTS: This article analyzes the physiological structures of the eyes, ocular diseases and its existing ocular preparations in sequence. Finally, this article reviews the development and trends of ocular microneedles in recent years, and summarizes and discusses the drugs of ocular microneedles as well as the future directions of development. At the same time, according to the inspiration of previous work, the concept of "microneedle with spinule" is proposed for the first time, and its advantages and limitations are discussed in the article. CONCLUSIONS: At present, the application of ocular microneedles still faces multiple challenges. The aspects of auxiliary devices, appearance, the properties of the matrix materials, and preparation technology of ophthalmic microneedle are crucial for their application in the treatment of eye diseases.

Anatomical Mechanisms of Leaf Blade Morphogenesis in Sasaella kogasensis 'Aureostriatus'.

There are limited studies on the cytology of bamboo leaf development from primordium to maturity. This study delves into the leaf morphological characteristics and growth patterns of Sasaella kogasensis 'Aureostriatus' and provides a three-dimensional anatomical analysis of cell division, expansion, and degradation. Leaves on the same branch develop bottom-up, while individual leaves develop the other way around. Like bamboo shoots and culms, the leaves follow a "slow-fast-slow" growth pattern, with longitudinal growth being predominant during their development. The growth zones of individual leaves included division, elongation, and maturation zones based on the distribution of growth space. By measuring 13,303 epidermal long cells and 3293 mesophyll cells in longitudinal sections of rapidly elongating leaves, we observed that in the rapid elongation phase (S4-S5), the division zone was located in the 1-2 cm segment at the bottom of the leaf blade and maintained a constant size, continuously providing new cells for leaf elongation, whereas in the late rapid elongation phase (S6), when the length of the leaf blade was approaching that of a mature leaf, its cells at the bottom of the blade no longer divided and were replaced by the ability to elongate. Furthermore, to gain an insight into the dynamic changes in the growth of the S. kogasensis 'Aureostriatus' leaves in the lateral and periclinal directions, the width and thickness of 1459 epidermal and 2719 mesophyll cells were counted in the mid-cross section of leaves at different developmental stages. The results showed that during the early stages of development (S1-S3), young leaves maintained vigorous division in the lateral direction, while periplasmic division gradually expanded from the bottom to the top of the leaf blade and the number of cell layers stabilized at S4. The meristematic tissues on both sides of the leaf were still able to divide at S4 but the frequency of the division gradually decreased, while cell division and expansion occurred simultaneously between the veins. At S6, the cells at the leaf margins and between the veins were completely differentiated and the width of the leaf blade no longer expanded. These findings revealed changes in cell growth anisotropically during the leaf development of S. kogasensis 'Aureostriatus' and demonstrated that leaf elongation was closely related to the longitudinal expansion of epidermal cells and proliferative growth of mesophyll cells, whereas the cell division of meristematic tissues and expansion of post-divisional cells contributed to the increases in blade width and thickness. The presented framework will facilitate a further exploration of the molecular regulatory mechanisms of leaf development in S. kogasensis 'Aureostriatus' and provide relevant information for developmental and taxonomic studies of bamboo plants.

Overview of molecular mechanisms of plant leaf development: a systematic review.

Leaf growth initiates in the peripheral region of the meristem at the apex of the stem, eventually forming flat structures. Leaves are pivotal organs in plants, serving as the primary sites for photosynthesis, respiration, and transpiration. Their development is intricately governed by complex regulatory networks. Leaf development encompasses five processes: the leaf primordium initiation, the leaf polarity establishment, leaf size expansion, shaping of leaf, and leaf senescence. The leaf primordia starts from the side of the growth cone at the apex of the stem. Under the precise regulation of a series of genes, the leaf primordia establishes adaxial-abaxial axes, proximal-distal axes and medio-lateral axes polarity, guides the primordia cells to divide and differentiate in a specific direction, and finally develops into leaves of a certain shape and size. Leaf senescence is a kind of programmed cell death that occurs in plants, and as it is the last stage of leaf development. Each of these processes is meticulously coordinated through the intricate interplay among transcriptional regulatory factors, microRNAs, and plant hormones. This review is dedicated to examining the regulatory influences of major regulatory factors and plant hormones on these five developmental aspects of leaves.

SPP excitation and coupling mechanism based on micro/nano fibers.

A hot trend in the development of optoelectronic devices is how to use the principle of surface plasmon resonance to enhance the performance of integrated photonics devices and achieve miniaturization. This paper proposes an accompanying waveguide coupling structure of micro/nano fibers, which consists of two parallel-placed micro/nano fibers (MNFs) coated with a silver film in the waist region and infused with a refractive index matching oil. In the overlapping region, there exists a segment of surface plasmon polaritons (SPPs) coupling area. The excitation and coupling characteristics of SPPs are studied through numerical simulation. Optimal coupling enhancement configuration is obtained by studying variables such as spacing distance, coupling length, and metal film thickness. A comparison is made with the SPP intensity of a single MNF, showing a 220% increase in electric field intensity, demonstrating its excellent coupling effect. By using this coupling structure, exploration of SPPs excitation and coupling mechanisms is enhanced, and structures resembling interferometric devices can be designed, providing new insights for high-performance miniaturized devices.

Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study.

BACKGROUND: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). METHODS: Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). RESULTS: No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. CONCLUSION: Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).

Comparative phylogenomic analyses and co-expression gene network reveal insights in flowering time and aborted meiosis in woody bamboo, Bambusa oldhamii 'Xia Zao' ZSX.

Woody bamboos have peculiar flowering characteristics with intervals ranging from several years to more than 100 years. Elucidating flowering time and reproductive development in bamboo could be beneficial for both humans and wildlife. To identity the mechanisms responsible for flowering time and embryo abortion in Bambusa oldhamii 'Xia Zao' ZSX, a transcriptome sequencing project was initiated to characterize the genes involved in developing flowers in this bamboo species. Morphological studies showed that pollen abortion in this bamboo species was mainly caused by a delay in tapetum degradation and abnormal meiotic process. Differential expression (DE) and optimized hierarchical clustering analyses identified three of nine gene expression clusters with decreasing expression at the meiosis of flowering stages. Together with enriched Gene Ontology Biological Process terms for meiosis, this suggests that their expression pattern may be associated with aborted meiosis in B. oldhamii 'Xia Zao'. Moreover, our large-scale phylogenomic analyses comparing meiosis-related transcripts of B. oldhamii 'Xia Zao' with well annotated genes in 22 representative angiosperms and sequence evolution analyses reveal two core meiotic genes NO EXINE FORMATION 1 (NFE1) and PMS1 with nonsense mutations in their coding regions, likely providing another line of evidence supporting embryo abortion in B. oldhamii 'Xia Zao'. Similar analyses, however, reveal conserved sequence evolution in flowering pathways such as LEAFY (LFY) and FLOWERING LOCUS T (FT). Seventeen orthogroups associated with flowering were identified by DE analyses between nonflowering and flowering culm buds. Six regulators found primarily in several connected network nodes of the photoperiod pathway were confirmed by mapping to the flowering time network in rice, such as Heading date (Hd3a) and Rice FT-like 1 (RFT1) which integrate upstream signaling into the downstream effectors. This suggests the existence of an intact photoperiod pathway is likely the key regulators that switch on/off flowering in B. oldhamii 'Xia Zao'.

Simulation study of a temperature-calibrated double-sided polished optical fiber SPR refractive index sensor.

The temperature of the environment directly affects the accuracy of refractive index (RI) measurement. Therefore, we propose a double-sided polished surface plasmon resonance (SPR) RI fiber sensor, which is available for simultaneous measurement of the RI and temperature in real time. The proposed sensor uses single-mode fiber as a special double-sided polishing structure. The double-sided polishing regions are coated with a gold-silver hybrid film; one side is additionally coated with graphene layers to increase detection sensitivity, and the other side is coated with polydimethylsiloxane on the metal layer for temperature sensing. The simulation result shows that in the range from 1.33 to 1.35, RI sensitivity reaches as high as 2600 nm/RIU. In the range from 15°C to 85°C, temperature sensitivity reaches as high as -3.5n m/∘ C. The full width at half maximum is 65 nm. Compared with previous studies, the sensitivity is slightly improved, and an excellent temperature compensation effect can be achieved. It is suitable for high-precision measurement of the environment and biochemical aspects.

Complete chloroplast genome sequence and phylogenetic analysis of Chimonobambusa sichuanensis (Bambusoideae).

Chimonobambusa sichuanensis is an ornamental shrubby bamboo endemic to southern China. In this study, the complete chloroplast genome (cpDNA) sequence of Chimonobambusa sichuanensis was first reported. The cpDNA is 139,594 bp in length, including a small single-copy (SSC) region of 12,820 bp and a large single-copy (LSC) region of 83,196 bp, which were separated by a pair of inverted repeat (IR) regions of 21,789 bp. The genome contains 140 genes, consisting of 93 protein-coding genes, seven ribosomal RNA (rRNA) genes, and 40 transfer RNA (tRNA) genes. The phylogenetic analysis showed that C. sichuanensis is highly clustered in the Phyllostachys clade, sister to C. tumidissinoda.

Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells.

Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3' UTR led to chronic cytokine production in memory T cells. This aberrant protein production did not result from increased expression and/or half-life of the mRNA. Instead, AREs blocked the recruitment of cytokine-encoding mRNA to ribosomes; this block depended on the ARE-binding protein ZFP36L2. Thus, AREs mediate repression of translation in mouse and human memory T cells by preventing undesirable protein production from pre-formed cytokine-encoding mRNAs in the absence of infection.

Defining the sequence requirements for the positioning of base J in DNA using SMRT sequencing.

Base J (ß-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. This highly restricted distribution must be co-determined by the thymidine hydroxylases (JBP1 and JBP2) that catalyze the initial step in J synthesis. To determine the DNA sequences recognized by JBP1/2, we used SMRT sequencing of DNA segments inserted into plasmids grown in Leishmania tarentolae. We show that SMRT sequencing recognizes base J in DNA. Leishmania DNA segments that normally contain J also picked up J when present in the plasmid, whereas control sequences did not. Even a segment of only 10 telomeric (GGGTTA) repeats was modified in the plasmid. We show that J modification usually occurs at pairs of Ts on opposite DNA strands, separated by 12 nucleotides. Modifications occur near G-rich sequences capable of forming G-quadruplexes and JBP2 is needed, as it does not occur in JBP2-null cells. We propose a model whereby de novo J insertion is mediated by JBP2. JBP1 then binds to J and hydroxylates another T 13 bp downstream (but not upstream) on the complementary strand, allowing JBP1 to maintain existing J following DNA replication.