Structuring restricted amorphous molecular chains in the reinforced cellulose film by uniaxial stretching.

The construction of the preferred orientation structure by stretching is an efficient strategy to fabricate high-performance cellulose film and it is still an open issue whether crystalline structure or amorphous molecular chain is the key factor in determining the enhanced mechanical performance. Herein, uniaxial stretching with constant width followed by drying in a stretching state was carried out to cellulose hydrogels with physical and chemical double cross-linking networks, achieving high-performance regenerated cellulose films (RCFs) with an impressive tensile strength of 154.5 MPa and an elastic modulus of 5.4 GPa. The hierarchical structure of RCFs during uniaxial stretching and drying was systematically characterized from micro- to nanoscale, including microscopic morphology, crystalline structure as well as relaxation behavior at a molecular level. The two-dimensional correlation spectra of dynamic mechanical analysis and Havriliak-Negami fitting results verified that the enhanced mechanical properties of RCFs were mainly attributed to the stretch-induced tight packing and restricted relaxation of amorphous molecular chains. The new insight concerning the contribution of molecular chains in the amorphous region to the enhancement of mechanical performance for RCFs is expected to provide valuable guidance for designing and fabricating high-performance eco-friendly cellulose-based films.

Genomic variation, environmental adaptation and feralization in ramie, an ancient fiber crop.

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop, ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and fertilization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, 915 accessions from 20 countries were gathered, comprising cultivars, major landraces, feral populations and wild progenitor. Based on whole genome resequencing of these accessions, the most comprehensive ramie genomic variation map to date was constructed. Phylogenetic, demographic, and admixture signal detection analyses indicate that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and wild progenitor or ancient landraces. Feral ramie has greater genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization are different from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches which are substantially different from the niche of the wild progenitor, and three environmental variables were associated with habitat-specific adaptation in feral ramie. Our findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea (Camellia sinensis var. assamica).

Chinese Assam tea (Camellia sinensis var. assamica) is an important tea crop with a long history of cultivation in Yunnan, China. Despite its potential value as a genetic resource, its genetic diversity and domestication/breeding history remain unclear. To address this issue, we genotyped 469 ancient tea plant trees representing 26 C. sinensis var. assamica populations, plus two of its wild relatives (six and three populations of C. taliensis and C. crassicolumna, respectively) using 16 nuclear microsatellite loci. Results showed that Chinese Assam tea has a relatively high, but comparatively lower gene diversity (HS = 0.638) than the wild relative C. crassicolumna (HS = 0.658). Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups, with considerable interspecific introgression. The Chinese Assam tea accessions clustered into three gene pools, corresponding well with their geographic distribution. However, NewHybrids analysis indicated that 68.48% of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools. In addition, 10% of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C. taliensis. Our results suggest that Chinese Assam tea was domesticated separately in three gene pools (Puer, Lincang and Xishuangbanna) in the Mekong River valley and that the hybrids were subsequently selected during the domestication process. Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex, our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Successful removal of a duodenal lesion in difficult location using "a sandwich method".

A 69-year-old woman was diagnosed with a duodenal adenoma near major duodenal papilla during cancer screening examination (Figure 1A). Therefore, endoscopic mucosal resection (EMR) was proposed to remove the duodenal lesion. Unfortunately, satisfactory visualization of the duodenal lesion was not obtained during gastroscopic operation. Unexpectedly, duodenoscopy provided optimal visualization of the duodenal lesion. Consequently, the "sandwich method" using duodenoscopy-gastroscopy-duodenoscopy was successfully performed to remove the challenging duodenal lesion. Firstly, the duodenoscopy was used to create a submucosal bleb through injecting saline containing 0.3 % indigo carmine. Subsequently, the gastroscopy with a transparent capwas used to remove the duodenal lesion with en bloc resection. Then, the duodenoscopy was reused to close the mucosal defect. Finally, pathologic examination showed a tubule-villous adenoma. The patient was recovered uneventfully, and discharged 2 days later.

Effects of Intrinsic Defects in Pt-Based Carbon Supports on Alkaline Hydrogen Evolution Reaction.

Carbon material has widely been utilized in the synthesis of efficient carbon-supported Pt (Pt/C) catalysts, in which the structural properties greatly influence the electrocatalytic performances of Pt/C catalysts. However, the effects of intrinsic defects in carbon supports on the performance of the alkaline hydrogen evolution reaction (HER) have not been systematically investigated. Herein, porous carbon supports with different degrees of intrinsic defects were prepared by a simple template-assisted strategy, and the resulting samples were systematically studied by various analytical methods. The results suggested that the presence of abundant intrinsic defects (vacancy and topological defects) in the carbon support was advantageous in terms of favoring the dispersion and anchoring of Pt species, promoting electron transfer between Pt atoms and the carbon support, and tuning the electronic states of Pt species. These features improved the HER performance of Pt/C catalysts. Compared to the nontemplate-assisted carbon-supported Pt catalyst (Pt/NTC) with an overpotential of 178 mV, the optimized template-assisted carbon-supported Pt catalyst (Pt/TC) exhibited a lower overpotential of 58 mV at 10 mA cm-2. Besides, the Pt/TC catalyst displayed better HER durability than the Pt/NTC catalyst owing to its strong metal-support interaction. The DFT calculations confirmed the important role played by intrinsic defects (vacancy and topological defects) in stabilizing Pt atoms, with Pt-C3 coordination identified as the most favorable structure for improving the HER performance of Pt. Overall, novel insights on the significant contribution of intrinsic defects in porous carbon supports on the HER performances of Pt/C catalysts were provided, useful for future design and fabrication of advanced carbon-supported catalysts or other carbon-based electrode materials.

Correlation Between Li-Fe Anti-Site and Memory Effect of LiFePO4 in Li-Ion Batteries.

In Li-ion batteries, the origin of memory effect in Al-doped Li4Ti5O12 has been revealed as the reversible Al-ion switching between 8a and 16c sites in the spinel structure, but it is still not clear about that for olivine LiFePO4, which is one of the most important cathode materials. In this work, a series of Na-doped and Ti-doped LiFePO4 are prepared in a high-temperature solid-state method, electrochemically investigated in Li-ion batteries and characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Magic-Angle-Spinning Nuclear Magnetic Resonance (MAS NMR). Compared with non-doped LiFePO4, the Ti doping can simultaneously suppress the memory effect and the Li-Fe anti-site, while they are simultaneously enhanced by the Na doping. Meanwhile, the Ti doping improves the electrochemical performance of LiFePO4, opposite to the Na doping. Accordingly, a schematic diagram of phase transition is proposed to interpret the memory effect of LiFePO4, in which the memory effect is attributed to the defect of Li-Fe anti-site.

Orexin facilitates the peripheral chemoreflex via corticotropin releasing hormone neurons projecting to the nucleus of the solitary tract.

We previously showed that orexin neurons are activated by hypoxia and facilitate the peripheral chemoreflex (PCR)-mediated hypoxic ventilatory response (HVR), mostly by promoting the respiratory frequency response. Orexin neurons project to the nucleus of the solitary tract (nTS) and the paraventricular nucleus of the hypothalamus (PVN). The PVN contributes significantly to the PCR and contains nTS-projecting corticotropin releasing hormone (CRH) neurons. We hypothesized that in male rats orexin neurons contribute to the PCR by activating nTS-projecting CRH neurons. We used neuronal tract tracing and immunohistochemistry (IHC) to quantify the degree that hypoxia activates PVN-projecting orexin neurons. We coupled this with orexin receptor (OxR) blockade with suvorexant (Suvo, 20 mg/kg, i.p.) to assess the degree that orexin facilitates the hypoxia-induced activation of CRH neurons in the PVN, including those projecting to the nTS. In separate groups of rats, we measured the PCR following systemic orexin 1 receptor (Ox1R) blockade (SB-334867;1 mg/kg) and specific Ox1R knockdown in PVN. OxR blockade with Suvo reduced the number of nTS and PVN neurons activated by hypoxia, including those CRH neurons projecting to nTS. Hypoxia increased the number of activated PVN-projecting orexin neurons but had no effect on the number of activated nTS-projecting orexin neurons. Global Ox1R blockade and partial Ox1R knockdown in the PVN significantly reduced the PCR. Ox1R knockdown also reduced the number of activated PVN neurons and the number of activated tyrosine-hydroxylase neurons in the nTS. Our findings suggest orexin facilitates the PCR via nTS-projecting CRH neurons expressing Ox1R.Significance Statement Previously we showed that orexin contributes to the peripheral chemoreflex (PCR), but the mechanisms underlying this effect remain unknown. Here we show that: 1) orexin receptor blockade reduces the activation of the PVN and nTS; 2) hypoxia activates orexin neurons that project to the PVN, but not those projecting to nTS; 3) orexin receptor blockade reduces the activation of nTS-projecting corticotrophin releasing hormone (CRH) neurons in the PVN; 4) orexin 1 receptor (Ox1R) blockade and specific Ox1R knockdown in the PVN reduce the strength of the PCR, and 5) Ox1R knockdown reduces the number of activated PVN neurons and tyrosine-hydroxylase neurons in the nTS. These findings suggest that PVN-projecting orexin neurons facilitate the PCR via Ox1R on nTS-projecting CRH neurons.

Deep genome skimming reveals the hybrid origin of Pseudosasa gracilis (Poaceae: Bambusoideae).

Pseudosasa gracilis (Poaceae: Bambusoideae) is a temperate woody bamboo species endemic to South-central China with a narrow distribution. Previous phylogenetic studies revealed an unexpected, isolated phylogenetic position of Ps. gracilis. Here we conducted phylogenomic analysis by sampling populations of Ps. gracilis and its sympatric species Ps. nanunica and Sinosasa polytricha reflecting different genomic signals, by deep genome skimming. Integrating molecular evidence from chloroplast genes and genome-wide SNPs, we deciphered the phylogenetic relationships of Ps. gracilis. Both plastid and nuclear data indicate that Ps. gracilis is more closely related to Sinosasa, which is discordant with the taxonomic treatment. To further explore this molecular-morphological conflict, we screened 411 "perfect-copy" syntenic genes to reconstruct phylogenies using both the concatenation and coalescent methods. We observed extensive discordance between gene trees and the putative species tree. A significant hybridization event was detected based on 411 genes from the D subgenome, showing Ps. gracilis was a hybrid descendant between Sinosasa longiligulata and Ps. nanunica, with 63.56% and 36.44% inheritance probabilities of each parent. Moreover, introgression events were detected in the C subgenome between Ps. gracilis and S. polytricha in the same distribution region. Our findings suggest that sympatric hybridization and introgression play a crucial role in the origin of Ps. gracilis. By providing an empirical example of bamboo of hybrid origin using comprehensive analyses based on genomic data from different inheritance systems and morphological characters, our study represents a step forward in understanding of reticulate evolution of bamboos.

Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

METTL5 promotes gastric cancer progression via sphingomyelin metabolism.

BACKGROUND: The treatment of gastric cancer (GC) has caused an enormous social burden worldwide. Accumulating studies have reported that N6-methyladenosine (m6A) is closely related to tumor progression. METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells. However, its aberrant regulation in GC has not been fully elucidated. AIM: To excavate the role of METTL5 in the development of GC. METHODS: METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples. The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays, colony formation assays, scratch healing assays, transwell assays and flow cytometry. The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model. The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification. Next, liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism, which was confirmed by Enzyme-linked immunosorbent assay and rescue tests. In addition, we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments. RESULTS: Our research revealed substantial upregulation of METTL5, which suggested a poor prognosis of GC patients. Increased METTL5 expression indicated distant lymph node metastasis, advanced cancer stage and pathological grade. An increased level of METTL5 correlated with a high degree of m6A methylation. METTL5 markedly promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 also promotes the growth of GC in animal models. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism, which implies that METTL5 may impact the development of GC via sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance. CONCLUSION: METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

Unprecedented variation pattern of plastid genomes and the potential role in adaptive evolution in Poales.

BACKGROUND: The plastid is the photosynthetic organelle in plant cell, and the plastid genomes (plastomes) are generally conserved in evolution. As one of the most economically and ecologically important order of angiosperms, Poales was previously documented to exhibit great plastomic variation as an order of photoautotrophic plants. RESULTS: We acquired 93 plastomes, representing all the 16 families and 5 major clades of Poales to reveal the extent of their variation and evolutionary pattern. Extensive variation including the largest one in monocots with 225,293 bp in size, heterogeneous GC content, and a wide variety of gene duplication and loss were revealed. Moreover, rare occurrences of three inverted repeat (IR) copies in angiosperms and one IR loss were observed, accompanied by short IR (sIR) and small direct repeat (DR). Widespread structural heteroplasmy, diversified inversions, and unusual genomic rearrangements all appeared in Poales, occasionally within a single species. Extensive repeats in the plastomes were found to be positively correlated with the observed inversions and rearrangements. The variation all showed a "small-large-moderate" trend along the evolution of Poales, as well as for the sequence substitution rate. Finally, we found some positively selected genes, mainly in C4 lineages, while the closely related lineages of those experiencing gene loss tended to have undergone more relaxed purifying selection. CONCLUSIONS: The variation of plastomes in Poales may be related to its successful diversification into diverse habitats and multiple photosynthetic pathway transitions. Our order-scale analyses revealed unusual evolutionary scenarios for plastomes in the photoautotrophic order of Poales and provided new insights into the plastome evolution in angiosperms as a whole.

Analysis of heavy metal and polycyclic aromatic hydrocarbon pollution characteristics of a typical metal rolling industrial site based on data mining.

With the transformation and upgrading of industries, the environmental problems caused by industrial residual contaminated sites are becoming increasingly prominent. Based on actual investigation cases, this study analyzed the soil pollution status of a remaining sites of the copper and zinc rolling industry, and found that the pollutants exceeding the screening values included Cu, Ni, Zn, Pb, total petroleum hydrocarbons and 6 polycyclic aromatic hydrocarbon monomers. Based on traditional analysis methods such as the correlation coefficient and spatial distribution, combined with machine learning methods such as SOM + K-means, it is inferred that the heavy metal Zn/Pb may be mainly related to the production history of zinc rolling. Cu/Ni may be mainly originated from the production history of copper rolling. PAHs are mainly due to the incomplete combustion of fossil fuels in the melting equipment. TPH pollution is speculated to be related to oil leakage during the industrial use period and later period of vehicle parking. The results showed that traditional analysis methods can quickly identify the correlation between site pollutants, while SOM + K-means machine learning methods can further effectively extract complex hidden relationships in data and achieve in-depth mining of site monitoring data.

Variations and reduction of plastome are associated with the evolution of parasitism in Convolvulaceae.

Parasitic lifestyle can often relax the constraint on the plastome, leading to gene pseudogenization and loss, and resulting in diverse genomic structures and rampant genome degradation. Although several plastomes of parasitic Cuscuta have  been reported, the evolution of parasitism in the family Convolvulaceae which is linked to structural variations and reduction of plastome has not been well investigated. In this study, we assembled and collected 40 plastid genomes belonging to 23 species representing four subgenera of Cuscuta and ten species of autotrophic Convolvulaceae. Our findings revealed nine types of structural variations and six types of inverted repeat (IR) boundary variations in the plastome of Convolvulaceae spp. These structural variations were associated with the shift of parasitic lifestyle, and IR boundary shift, as well as the abundance of long repeats. Overall, the degradation of Cuscuta plastome proceeded gradually, with one clade exhibiting an accelerated degradation rate. We observed five stages of gene loss in Cuscuta, including NAD(P)H complex → PEP complex → Photosynthesis-related → Ribosomal protein subunits → ATP synthase complex. Based on our results, we speculated that the shift of parasitic lifestyle in early divergent time promoted relaxed selection on plastomes, leading to the accumulation of microvariations, which ultimately resulted in the plastome reduction. This study provides new evidence towards a better understanding of plastomic evolution, variation, and reduction in the genus Cuscuta.

Phylogenomic profiles of whole-genome duplications in Poaceae and landscape of differential duplicate retention and losses among major Poaceae lineages.

Poaceae members shared a whole-genome duplication called rho. However, little is known about the evolutionary pattern of the rho-derived duplicates among Poaceae lineages and implications in adaptive evolution. Here we present phylogenomic/phylotranscriptomic analyses of 363 grasses covering all 12 subfamilies and report nine previously unknown whole-genome duplications. Furthermore, duplications from a single whole-genome duplication were mapped to multiple nodes on the species phylogeny; a whole-genome duplication was likely shared by woody bamboos with possible gene flow from herbaceous bamboos; and recent paralogues of a tetraploid Oryza are implicated in tolerance of seawater submergence. Moreover, rho duplicates showing differential retention among subfamilies include those with functions in environmental adaptations or morphogenesis, including ACOT for aquatic environments (Oryzoideae), CK2ß for cold responses (Pooideae), SPIRAL1 for rapid cell elongation (Bambusoideae), and PAI1 for drought/cold responses (Panicoideae). This study presents a Poaceae whole-genome duplication profile with evidence for multiple evolutionary mechanisms that contribute to gene retention and losses.

Frustrated Lewis pair catalyst realizes efficient green diesel production.

Hydrotreating renewable oils over sulfided metal catalysts is commercially applied to produce green diesel, but it requires a continuous sulfur replenishment to maintain catalyst activity, which inevitably results in sulfur contamination and increases production costs. We report a robust P-doped NiAl-oxide catalyst with frustrated Lewis pairs (i.e., P atom bonded with the O atom acts as an electron donor, while the spatially separated Ni atom acts as an electron acceptor) that allows efficient green diesel production without sulfur replenishment. The catalyst runs more than 500 h at a weight hourly space velocity (WHSV) of 28.3 h-1 without deactivation (methyl laurate as a model compound), and is able to completely convert a real feedstock of soybean oil to diesel-range hydrocarbons with selectivity >90% during 500 h of operation. This work is expected to open up a new avenue for designing non-sulfur catalysts that can make the green diesel production greener.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.