METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

nBEST: Deep-learning-based non-human primates Brain Extraction and Segmentation Toolbox across ages, sites and species.

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.

The Identification and Gene Mapping of Spotted Leaf Mutant spl43 in Rice.

Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.

Boarding Oncolytic Viruses onto Tumor-Homing Bacterium-Vessels for Augmented Cancer Immunotherapy.

Oncolytic viruses (OVs) have been widely used as anticancer therapeutics because of their systemic immune responses during viral replication. However, the low enrichment of OVs within tumors and limited immune activation have hindered their clinical application. Herein, we proposed the concept of bacteria-assisted targeting of OVs to tumors, with liposome-cloaked oncolytic adenoviruses (OAs) conjugated onto tumor-homing Escherichia coli BL21 (designated as E. coli-lipo-OAs) for enhanced cancer immunotherapy. Notably, the enrichment of OAs transported by self-propelled bacterial microbe vehicles in E. coli-lipo-OAs in a nonsmall cell lung tumor can be potentiated by more than 170-fold compared with that of intravenously injected bare OAs. In vivo studies further revealed that E. coli-lipo-OAs administered intravenously significantly enhanced antitumor immunity through bacterial-viral-augmented immune responses. Our findings suggest that the self-driving microbe vehicle as a systemic delivery system for OVs can be a potent platform for developing future anticancer biotherapeutics at the clinical level.

Comparative transcriptome analysis of experimental cryptorchidism: of mice and cynomolgus monkeys.

In most mammalian species, the testis descends from the abdomen into the scrotum during fetal or neonatal life. The failure of testicular descent, a pathological condition known as cryptorchidism, has long been the subject of scientific interest in a wide range of fields, including medicine, developmental biology, and evolutionary biology. In this study, we analyzed global gene expression changes associated with experimental cryptorchidism in mice by using RNA-seq. A total of 453 differentially expressed genes were identified, of which 236 genes were upregulated, and 217 genes were downregulated. Gene ontology, pathway, and gene network analysis highlighted the activation of inflammatory response in experimental cryptorchidism. By examining the promoter regions of differentially expressed genes, we identified 12 causal transcription factors. In addition, we also induced experimental cryptorchidism in two cynomolgus monkeys and performed RNA-seq. A cross-species comparison was performed at the gene expression level. Our study provides a valuable resource for further understanding the molecular mechanisms of cryptorchidism in mammals.

Mapping developmental paths of monkey primordial germ-like cells differentiation from pluripotent stem cells by single cell ribonucleic acid sequencing analysis†.

The induction of primordial germ-like cells (PGCLCs) from pluripotent stem cells (PSCs) provides a powerful system to study the cellular and molecular mechanisms underlying germline specification, which are difficult to study in vivo. The studies reveal the existence of a species-specific mechanism underlying PGCLCs between humans and mice, highlighting the necessity to study regulatory networks in more species, especially in primates. Harnessing the power of single-cell RNA sequencing (scRNA-seq) analysis, the detailed trajectory of human PGCLCs specification in vitro has been achieved. However, the study of nonhuman primates is still needed. Here, we applied an embryoid body (EB) differentiation system to induce PGCLCs specification from cynomolgus monkey male and female PSCs, and then performed high throughput scRNA-seq analysis of approximately 40 000 PSCs and cells within EBs. We found that EBs provided a niche for PGCLCs differentiation by secreting growth factors critical for PGCLC specification, such as bone morphogenetic protein 2 (BMP2), BMP4, and Wnt Family Member 3. Moreover, the developmental trajectory of PGCLCs was reconstituted, and gene expression dynamics were revealed. Our study outlines the roadmap of PGCLC specification from PSCs and provides insights that will improve the differentiation efficiency of PGCLCs from PSCs.

Genomic architecture of heterosis for yield traits in rice.

Increasing grain yield is a long-term goal in crop breeding to meet the demand for global food security. Heterosis, when a hybrid shows higher performance for a trait than both parents, offers an important strategy for crop breeding. To examine the genetic basis of heterosis for yield in rice, here we generate, sequence and record the phenotypes of 10,074 F2 lines from 17 representative hybrid rice crosses. We classify modern hybrid rice varieties into three groups, representing different hybrid breeding systems. Although we do not find any heterosis-associated loci shared across all lines, within each group, a small number of genomic loci from female parents explain a large proportion of the yield advantage of hybrids over their male parents. For some of these loci, we find support for partial dominance of heterozygous locus for yield-related traits and better-parent heterosis for overall performance when all of the grain-yield traits are considered together. These results inform on the genomic architecture of heterosis and rice hybrid breeding.

The Gain-of-Function Mutation, OsSpl26, Positively Regulates Plant Immunity in Rice.

Rice spotted-leaf mutants are ideal materials to study the molecular mechanism underlying programmed cell death and disease resistance in plants. LOC_Os07g04820 has previously been identified as the candidate gene responsible for the spotted-leaf phenotype in rice Spotted-leaf 26 (Spl26) mutant. Here, we cloned and validated that LOC_Os07g04820 is the locus controlling the spotted-leaf phenotype of Spl26 by reverse functional complementation and CRISPR/Cas9-mediated knockout of the mutant allele. The recessive wild-type spl26 allele (Oryza sativa spotted-leaf 26, Osspl26) is highly conservative in grass species and encodes a putative G-type lectin S-receptor-like serine/threonine protein kinase with 444 amino acid residuals. OsSPL26 localizes to the plasma membrane and can be detected constitutively in roots, stems, leaves, sheaths and panicles. The single base substitution from T to A at position 293 leads to phenylalanine/tyrosine replacement at position 98 in the encoded protein in the mutant and induces excessive accumulation of H2O2, leading to oxidative damage to cells, and finally, formation of the spotted-leaf phenotype in Spl26. The formation of lesions not only affects the growth and development of the plants but also activates the defense response and enhances the resistance to the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae. Our results indicate that the gain-of-function by the mutant allele OsSpl26 positively regulates cell death and immunity in rice.

miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer.

BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. METHODS: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. RESULTS: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. CONCLUSION: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.

Conductivity enhancement of silver nanowire networks via simple electrolyte solution treatment and solvent washing.

As a promising replacement material for indium tin oxide in flexible electronics, silver nanowires (AgNWs) usually need complicated post-treatment to reduce the high contact resistance across the intersections when used as transparent conductive films. In this work, a widely applicable nano-joining method for improving the overall conductivity of AgNW networks with different kinds of electrolyte solutions is presented. By treatment with an electrolyte solution with appropriate ionic strengths, the insulating surfactant layer (polyvinylpyrrolidone, PVP) on the AgNWs could be desorbed, and the AgNW network could be densified. The sheet resistance of the AgNW film on a glass slide is reduced by 60.9% (from 67.5 to 26.4 Ohm sq-1) with a transmittance of 92.5%. High-resolution transmission electron microscopy analysis indicates that atomic diffusion occurs at the intersection of two AgNWs. Thus, metallurgical bonding on the nanometer scale is achieved across the junctions of the AgNWs, leading to a significant enhancement in the conductivity of the AgNW network.

Comparative Evaluation of Soluble and Insoluble-Bound Phenolics and Antioxidant Activity of Two Chinese Mistletoes.

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble and insoluble-bound phenolic extracts from CMs hosted by Camellia assamica (Mast.) Chang (CMC) and Pyrus, i, f. (CMP) were compared. Phenolic compounds in CMC and CMP were identified and quantified using high-performance liquid chromatography (HPLC). The results indicated that the TPC of soluble phenolic extracts was higher than insoluble-bound phenolic counterparts in both CMC and CMP. In addition, the TPC of soluble, insoluble-bound and total phenolic fractions (9.91 ± 0.23, 4.59 ± 0.27 and 14.50 ± 0.35 µmol ferulic acid equivalents per gram (FAE/g) dry sample) extracted from CMP were higher than those extracted from CMC. The soluble phenolic extracts in CMP showed higher antioxidant activities than those in CMC. Eighteen phenolic compounds from soluble and insoluble-bound phenolic extracts from the CMs were identified and quantified by HPLC. This study indicates that CMC and CMP, especially the latter, could be sources of antioxidants in human health care.

Cell Recognition Molecule L1 Regulates Cell Surface Glycosylation to Modulate Cell Survival and Migration.

Background: Cell recognition molecule L1 (L1) plays an important role in cancer cell differentiation, proliferation, migration and survival, but its mechanism remains unclear. Methodology/Principal: Our previous study has demonstrated that L1 enhanced cell survival and migration in neural cells by regulating cell surface glycosylation. In the present study, we show that L1 affected cell migration and survival in CHO (Chinese hamster ovary) cell line by modulation of sialylation and fucosylation at the cell surface via the PI3K (phosphoinositide 3-kinase) and Erk (extracellularsignal-regulated kinase) signaling pathways. Flow cytometry analysis indicated that L1 modulated cell surface sialylation and fucosylation in CHO cells. Activated L1 upregulated the protein expressions of ST6Gal1 (ß-galactoside α-2,6-sialyltransferase 1) and FUT9 (Fucosyltransferase 9) in CHO cells. Furthermore, activated L1 promoted CHO cells migration and survival as shown by transwell assay and MTT assay. Inhibitors of sialylation and fucosylation blocked L1-induced cell migration and survival, while decreasing FUT9 and ST6Gal1 expressions via the PI3K-dependent and Erk-dependent signaling pathways. Conclusion : L1 modulated cell migration and survival by regulation of cell surface sialylation and fucosylation via the PI3K-dependent and Erk-dependent signaling pathways.

Knowledge and Awareness of Cervical Cancer, Human Papillomavirus (HPV), and HPV Vaccine Among HPV-Infected Chinese Women.

BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV vaccine was very low. Targeted communication is very important among populations in which knowledge gaps exist in order to promote dialogue about the vaccine among patients and their healthcare providers.

Nicotine-degrading microorganisms and their potential applications.

Nicotine-degrading microorganisms (NDMs) are a special microbial group which can use nicotine as the sole carbon and nitrogen source for growth. Since the 1950s, the bioconversion of nicotine by microbes has received increasing attention, and several NDMs have been identified, such as Arthrobacter nicotinovorans, Microsporum gypseum, Pellicularia filamentosa JTS-208, and Pseudomonas sp. 41. In recent years, increasing numbers of NDMs have been isolated and identified from tobacco plantation soil, leaf, and tobacco waste. Meanwhile, the metabolic pathway and degradation mechanism of nicotine have been elucidated in several NDMs, such as A. nicotinovorans, Agrobacterium tumefaciens S33, Aspergillus oryzae, and Pseudomonas putida S16. Moreover, several NDMs have been used in improving the quality of cigarettes, treating tobacco waste, and producing valuable intermediates of nicotine. Here, we summarize the diversity, phylogenetic analysis, and potential applications of NDMs.

[Study on rapid identification of medicinal plants of Paris polyphylla from different origin areas by NIR spectroscopy].

Based on near infrared spectroscopy, seventy samples of wild medicinal plants of paris polyphylla from Guizhou, Guangxi and Yunnan Provinces were collected to identify their geographical origins. Multiplication signal correction (MSC), standard normal variate (SNV), first derivative (FD), second derivative (SD), savitzky-Golay filter (SG), and Norris derivative filter (ND) were conducted to optimize the original spectra of fifty samples of training set. The results showed that the method MSC combined with SD and ND presented the best results of spectra pretreatment. According to spectrum standard deviation, spectrum range (7 450-4 050 cm(-1)) was chosen and principal component analysis-mahalanobis distance (PCA-MD) method was used to build the model. Its first three principal components, i. e. cumulative contribution, determination coefficient (R2), root-mean-square error of calibration (RMSEC) and root-mean-square error of prediction (RMSEP) were 89.44%, 97.58%, 0.179 6 and 0.266 4, respectively, and the prediction accuracy is 90%. Furthermore, according to variable importance plot (VIP), spectrum range (7 135.33-4 007.35 cm(-1)) was chosen and partial least square discrimination analysis (PLS-DA) was applied to establish the model. Its first three principal components cumulative contribution, R2, RMSEC and RMSEP were 89.28%, 95.88%, 0.234 8 and 0.348 2, respectively, and the prediction accuracy is 100%. Comparing the two methods, we found that spectrum range chosen by VIP and model built by PLS-DA could provide greater accuracy in identifying paris polyphylla from different origin areas. The method supplied foundation for authenticity and quality evaluation of traditional Chinese medicine.

Micro-to-Nano Oncolytic Microbial System Shifts from Tumor Killing to Tumor Draining Lymph Nodes Remolding for Enhanced Immunotherapy.

Because the tumor-draining lymph nodes (TDLNs) microenvironment is commonly immunosuppressive, oncolytic microbe-induced tumor antigens aren't sufficiently cross-primed tumor specific T cells through antigen-presenting cells (e.g., dendritic cells (DCs)) in TDLNs. Herein, this work develops the micro-to-nano oncolytic microbial therapeutics based on pyranose oxidase (P2 O) overexpressed Escherichia coli (EcP) which are simultaneously encapsulated by PEGylated mannose and low-concentrated photosensitizer nanoparticles (NPs). Following administration, P2 O from this system generates toxic hydrogen peroxide for tumor regression and leads to the release of tumor antigens. The "microscale" EcP is triggered, following exposure to the laser irradiation, to secrete the "nanoscale" bacterial outer membrane vesicles (OMVs). The enhanced TDLNs delivery via OMVs significantly regulates the TDLNs immunomicroenvironment, promoting the maturation of DCs to potentiate tumor antigen-specific T cells immune response. The micro-to-nano oncolytic microbe is leveraged to exert tumor killing and remold TDLNs for initiating potent activation of DCs, providing promising strategies to facilitate microbial cancer vaccination.

Transgenic rhesus monkeys produced by gene transfer into early-cleavage-stage embryos using a simian immunodeficiency virus-based vector.

The development of transgenic technologies in monkeys is important for creating valuable animal models of human physiology so that the etiology of diseases can be studied and potential therapies for their amelioration may be developed. However, the efficiency of producing transgenic primate animals is presently very low, and there are few reports of success. We have developed an improved methodology for the production of transgenic rhesus monkeys, making use of a simian immunodeficiency virus (SIV)-based vector that encodes EGFP and a protocol for infection of early-cleavage-stage embryos. We show that infection does not alter embryo development. Moreover, the timing of infection, either before or during embryonic genome activation, has no observable effect on the level and stability of transgene expression. Of 70 embryos injected with concentrated virus at the one- to two-cell stage or the four- to eight-cell stage and showing fluorescence, 30 were transferred to surrogate mothers. One transgenic fetus was obtained from a fraternal triple pregnancy. Four infant monkeys were produced from four singleton pregnancies, of which two expressed EGFP throughout the whole body. These results demonstrate the usefulness of SIV-based lentiviral vectors for the generation of transgenic monkeys and improve the efficiency of transgenic technology in nonhuman primates.

Role of Interleukin-22 in ulcerative colitis.

Ulcerative Colitis (UC) is a chronic disease, in the progression of which an immune overreaction may play an important role. IL-22 is a member of the IL-10 superfamily of cytokines and is pleiotropic in immune regulation and inflammatory responses. IL-22 can produce protective effects, promote wound healing and tissue regeneration, while it can also induce inflammatory reactions when it is chronically overexpressed. Extensive literatures reported that IL-22 played an essential role in the pathogenic development of UC. IL-22 participates in the whole disease process of UC involving signaling pathways, gene expression regulation, and intestinal flora imbalance, making IL-22 a possible candidate for the treatment of UC. In this paper, the latest knowledge to further elucidate the role of IL-22 in UC was summarized and analyzed.

Self-assembled short peptides: Recent advances and strategies for potential pharmaceutical applications.

Self-assembled short peptides have intrigued scientists due to the convenience of synthesis, good biocompatibility, low toxicity, inherent biodegradability and fast response to change in the physiological environment. Therefore, it is necessary to present a comprehensive summary of the recent advances in the last decade regarding the construction, route of administration and application of self-assembled short peptides based on the knowledge on their unique and specific ability of self-assembly. Herein, we firstly explored the molecular mechanisms of self-assembly of short peptides, such as non-modified amino acids, as well as Fmoc-modified, N-functionalized, and C-functionalized peptides. Next, cell penetration, fusion, and peptide targeting in peptide-based drug delivery were characterized. Then, the common administration routes and the potential pharmaceutical applications (drug delivery, antibacterial activity, stabilizers, imaging agents, and applications in bioengineering) of peptide drugs were respectively summarized. Last but not least, some general conclusions and future perspectives in the relevant fields were briefly listed. Although with certain challenges, great opportunities are offered by self-assembled short peptides to the fascinating area of drug development.