An Intramolecular Rotor-Bridged Dimeric Cyanine Photothermal Transducer for Efficient Near-Infrared II Fluorescence Imaging-Guided Mitochondria-Targeted Phototherapy.

Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.

An Active Self-Mitochondria-Targeting Cyanine Immunomodulator for Near-Infrared II Fluorescence Imaging-Guided Synergistic Photodynamic Immunotherapy.

Photodynamic therapy targeting mitochondria represents a promising therapeutic strategy for fighting diverse types of cancers. However, the currently available photosensitizers (PSs) suffer from insufficient therapeutic potency, limited mitochondria delivery efficiency, and the inability to treat invisible metastatic distal cancers. Herein, an active self-mitochondria-targeting heptapeptide cyanine (HCy) immunomodulator (I2HCy-QAP) is reported for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic immunotherapy of primary and distal metastatic cancers. The I2HCy-QAP is designed by introducing a quaternary ammonium salt with a phenethylamine skeleton (QAP) into the iodinated HCy photosensitizer. The I2HCy-QAP can precisely target mitochondria due to the lipophilic cationic QAP unit, present strong NIR-II fluorescence tail emission, and effectively generate singlet oxygen 1O2 under NIR laser irradiation, thereby inducing mitochondria-targeted damages and eliciting strong systemic immunogenic cell death immune responses. The combination of the I2HCy-QAP-mediated photodynamic immunotherapy with anti-programmed death-1 antibody therapy achieves remarkable therapeutic efficacy against both primary and distal metastatic cancers with significant inhibition of lung metastasis in a triple-negative breast cancer model. This work provides a new concept for designing high-performance NIR emissive cyanine immunomodulators for NIR-II fluorescence-guided photodynamic immunotherapy.

FpPEX5 and FpPEX7 are involved in the growth, reproduction, DON toxin production, and pathogenicity in Fusarium pseudograminearum.

Fusarium crown rot, caused by Fusarium pseudograminearum, is a devastating disease affecting the yield and quality of cereal crops. Peroxisomes are single-membrane organelles that play a critical role in various biological processes in eukaryotic cells. To functionally characterise peroxisome biosynthetic receptor proteins FpPEX5 and FpPEX7 in F. pseudograminearum, we constructed deletion mutants, ΔFpPEX5 and ΔFpPEX7, and complementary strains, ΔFpPEX5-C and ΔFpPEX7-C, and analysed the functions of FpPEX5 and FpPEX7 proteins using various phenotypic observations. The deletion of FpPEX5 and FpPEX7 resulted in a significant deficiency in mycelial growth and conidiation and blocked the peroxisomal targeting signal 1 and peroxisomal targeting signal 2 pathways, which are involved in peroxisomal matrix protein transport, increasing the accumulation of lipid droplets and reactive oxygen species. The deletion of FpPEX5 and FpPEX7 may reduce the formation of toxigenic bodies and decrease the pathogenicity of F. pseudograminearum. These results indicate that FpPEX5 and FpPEX7 play vital roles in the growth, asexual reproduction, virulence, and fatty acid utilisation of F. pseudograminearum. This study provides a theoretical basis for controlling stem rot in wheat.

The Role of Solution Aggregation Property toward High-Efficiency Non-Fullerene Organic Photovoltaic Cells.

In organic photovoltaic cells, the solution-aggregation effect (SAE) is long considered a critical factor in achieving high power-conversion efficiencies for polymer donor (PD)/non-fullerene acceptor (NFA) blend systems. However, the underlying mechanism has yet to be fully understood. Herein, based on an extensive study of blends consisting of the representative 2D-benzodithiophene-based PDs and acceptor-donor-acceptor-type NFAs, it is demonstrated that SAE shows a strong correlation with the aggregation kinetics during solidification, and the aggregation competition between PD and NFA determines the phase separation of blend film and thus the photovoltaic performance. PDs with strong SAEs enable earlier aggregation evolutions than NFAs, resulting in well-known polymer-templated fibrillar network structures and superior PCEs. With the weakening of PDs' aggregation effects, NFAs, showing stronger tendencies to aggregate, tend to form oversized domains, leading to significantly reduced external quantum efficiencies and fill factors. These trends reveal the importance of matching SAE between PD and NFA. The aggregation abilities of various materials are further evaluated and the aggregation ability/photovoltaic parameter diagrams of 64 PD/NFA combinations are provided. This work proposes a guiding criteria and facile approach to match efficient PD/NFA systems.

[Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept].

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.

Regulatory Mechanism of Peroxisome Number Reduction Caused by FgPex4 and FgPex22-like Deletion in Fusarium graminearum.

Peroxisomes are single-membrane-bound organelles that play critical roles in eukaryotic cellular functions. Peroxisome quantity is a key factor influencing the homeostasis and pathogenic processes of pathogenic fungi. The aim of the present study was to investigate the underlying mechanisms of the reduction in number of peroxisomes in Fusarium graminearum consequent to FgPex4 and FgPex22-like deletion. The number of peroxisomes decreased by 40.55% and 39.70% when FgPex4 and FgPex22-like, respectively, were absent. Peroxisome biogenesis-related proteins, as well as inheritance- and division-related dynamin-like proteins were reduced at the transcriptional level in the mutant strains. In addition, the degree of pexophagy was intensified and the accumulation of ubiquitinated FgPex5 was also increased in F. graminearum when FgPex4 or FgPex22-like was absent. The findings suggest that FgPex4 and FgPex22-like influence the number of peroxisomes by influencing peroxisome biogenesis and pexophagy.

A Study on the Contact Characteristics of Tires-Roads Based on Pressure-Sensitive Film Technology.

Tire-road characteristics are a critical focus of research in the automotive and transportation industries. On the one hand, the research can help optimize tires' structural design; on the other hand, it can analyze the mechanical response of the pavement structure under the vehicle load. In addition, the non-uniformity distribution of the tire ground stress will also have a direct impact on the skid resistance, which determines the driving safety. Due to the limitation of testing technology, the measurement of tire ground pressure was mainly carried out on a flat test platform, ignoring the roughness of the actual pavement surface texture. The tire-road contact characteristics research on the macro-texture and micro-texture of asphalt pavement needs to be broken through. A high-precision pressure-sensitive film measurement system is utilized to examine the actual contact characteristics between two types of automobile tires and three types of asphalt pavement in this paper. The influence law of pavement texture and patterned tires on the contact area and stress was explored, and the concentration effect of tire-road contact stress was evaluated. The results indicate that the contact area of grounding tires exhibits a nearly linear relationship with tire inflation pressure and load. Notably, the change in load has a more significant influence on the contact area than tire inflation pressure. On asphalt pavement, the contact reduction rate decreases by approximately 5-10% for block pattern tires and 10-15% for longitudinal pattern tires. Furthermore, as the texture depth of the pavement increases, the contact area between tires and the pavement texture decreases. The actual tire-road interface experiences significant stress concentration due to the embedding and meshing effects between the tire and road surface. Even on a flat steel surface, the peak stress at the edge of the tread block exceeds the 0.7 MPa design load, which is about 2.5-3 times higher than the design uniform load. The peak stress between the tire and asphalt pavement reaches 4-10 times the design uniform load, with a rising trend as the pavement texture depth increases. This study can provide relevant experimental technical support for tire design and functional design of asphalt pavement.

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins.

Membrane proteins are a crucial class of therapeutic targets that remain challenging to modulate using traditional occupancy-driven inhibition strategies or current proteolysis-targeting degradation approaches. Here, we report that the inherent endolysosomal sorting machinery can be harnessed for the targeted degradation of membrane proteins. A new degradation technique, termed signal-mediated lysosome-targeting chimeras (SignalTACs), was developed by genetically fusing the signaling motif from the cation-independent mannose-6-phosphate receptor (CI-M6PR) to a membrane protein binder. Antibody-based SignalTACs were constructed with the CI-M6PR signal peptides fused to the C-terminus of both heavy and light chains of IgG. We demonstrated the scope of this platform technology by degrading five pathogenesis-related membrane proteins, including HER2, EGFR, PD-L1, CD20, and CD71. Furthermore, two simplified constructs of SignalTACs, nanobody-based and peptide-based SignalTACs, were created and shown to promote the lysosomal degradation of target membrane proteins. Compared to the parent antibodies, SignalTACs exhibited significantly higher efficiency in inhibiting tumor cell growth both in vitro and in vivo. This work provides a simple, general, and robust strategy for degrading membrane proteins with molecular precision and may represent a powerful platform with broad research and therapeutic applications.

Soybean balanced the growth and defense in response to SMV infection under different light intensities.

Light is essential for the growth and defense of soybean. It is not clear how soybeans adjust their defenses to different light environments with different cropping patterns. The mechanism of soybean response to Soybean mosaic virus (SMV) infection under different light intensities was analyzed by RNA-seq sequencing method. Enrichment analysis illustrated that most defense-related genes were down-regulated in the dark and the shade, and up-regulated under hard light and normal light. Soybean can resist SMV infection mainly by activating salicylic acid signaling pathway. Light is essential for activating salicylic acid defense signaling pathways. With the increase of light intensity, the oxidative damage of soybean leaves was aggravated, which promoted the infection of virus. When light was insufficient, the growth of soybean was weak, and the plant-pathogen interaction pathway, MAPK pathway and hormone defense pathway in infected soybean was inhibited. Under hard light, some defense genes in infected soybean were down-regulated to reduce the degree of oxidative damage. The expression of differentially expressed genes was verified by real-time fluorescence quantitative RT-PCR. In order to adapt to the change of light intensity, soybean balanced allocation of resources between growth and defense through a series regulation of gene expression. The results of this study will provide a theoretical basis for the research of SMV resistance in intercropping soybean.

Taugt17b1 Overexpression in Trichoderma atroviride Enhances Its Ability to Colonize Roots and Induce Systemic Defense of Plants.

Trichoderma atroviride, a soil fungus, has important applications in the biocontrol of plant diseases. Glycosyltransferases enhance the root colonization ability of Trichoderma spp. This study aimed to functionally characterize glycosyltransferase Taugt17b1 in T. atroviride. We investigated the effect of Taugt17b1 overexpression in T. atroviride H18-1-1 on its biocontrol properties, especially its ability to colonize roots. Our results demonstrated that the overexpression of the Taugt17b1 increases the T. atroviride colony growth rate, improves its root colonization ability, promotes the growth and activity of the defensive enzymatic system of plants, and prevents plant diseases. This study put forth a new role of T. atroviride glycosyltransferase and furthered the understanding of the mechanisms by which fungal biocontrol agents exert their effect.

Characterization and Expression Analysis of Four Cadmium-Tolerance-Associated Genes of Avicennia marina (Forsk.).

Mangroves colonize the intertidal area of estuaries (e.g., Pichavaram, Payardia, and Mai Po) with remarkable cadmium (Cd) pollution. A study on the mechanism of mangrove plant response to Cd pollution can help to understand the adaptive characteristics of plants under Cd stress. This study explored the roles of peroxidase (PRX), pectate lyase (PL), and phytosulfokine (PSK) genes in cadmium tolerance of mangrove Avicennia marina. Full-length sequences of four genes (i.e., AmPRX1, AmPRX2, AmPL, and AmPSK) associated with metal tolerance were identified with suppression subtractive hybridization and rapid amplification of cDNA ends. These genes showed the characteristic features of the respective protein family, indicating functions similar to other plant proteins. Real-time quantitative PCR analysis demonstrated that cadmium exposure resulted in differences in expression patterns among the tissues. Our findings emphasize the complex regulatory mechanism of these four genes in response to trace metal pollution and reveal their functions in metabolic signaling during the stress response.

Complete genome sequence of Bacillus Licheniformis NWMCC0046, a candidate for the laundry industry.

In this study, selected properties of protease and the complete genome sequence of Bacillus licheniformis NWMCC0046 were investigated, to discover laundry applications and other potential probiotic properties of this strain. Partial characterization of B. licheniformis NWMCC0046 showed that its protease has good activity both in alkaline environments and at low temperatures. Also, the protease is compatible with commercial detergents and can be used as a detergent additive for effective stain removal at low temperatures. The complete genome sequence of B. licheniformis NWMCC0046 is comprised of a 4,321,565 bp linear chromosome with a G + C content of 46.78% and no plasmids. It had 4504 protein-encoding genes, 81 transfer RNA (tRNA) genes, and 24 ribosomal RNA (rRNA) genes. Genomic analysis revealed genes involved in exocellular enzyme production and probiotic properties. In addition, genomic sequence analysis revealed specific genes encoding carbohydrate metabolism pathways, resistance, and cold adaptation capacity. Overall, protease properties show its potential as a detergent additive enzyme. The complete genome sequence information of B. licheniformis NWMCC0046 was obtained, and functional prediction revealed its numerous probiotic properties.

The somatic embryogenesis receptor kinase TaSERK1 participates in the immune response to Rhizoctonia cerealis infection by interacting and phosphorylating the receptor-like cytoplasmic kinase TaRLCK1B in wheat.

The sharp eyespot, caused by necrotrophic pathogen Rhizoctonia cerealis, often causes serious yield loss in wheat (Triticum aestivum). However, the mechanisms underlying wheat resistant responses to the pathogen are still limited. In this study, we performed a genome-wide analysis of somatic embryogenesis receptor kinase (SERK) family in wheat. As a result, a total of 26 TaSERK candidate genes were identified from the wheat genome. Only 6 TaSERK genes on the chromosomes 2A, 2B, 2D, 3A, 3B, and 3D showed obvious heightening expression patterns in resistant wheat infected with R. cerealis compared than those un-infected wheat. Of them, the transcripts of 3 TaSERK1 homoeologs on the chromosomes 2A, 2B, and 2D were significantly up-regulated in the highest level compared to other TaSERKs. Importantly, silencing of TaSERK1 significantly impaired wheat resistance to sharp eyespot. Further bio-molecular assays showed that TaSERK1 could interact with the defence-associated receptor-like cytoplasmic kinase TaRLCK1B, and phosphorylated TaRLCK1B. Together, the results suggest that TaSERK1 mediated resistance responses to R. cerealis infection by interacting and phosphorylating TaRLCK1B in wheat. This study sheds light on the understanding of the wheat SERKs in the innate immunity against R. cerealis, and provided a theoretical fulcrum to identify candidate resistant genes for improving wheat resistance against sharp eyespot in wheat.

3% nebulized hypertonic saline versus normal saline for infants with acute bronchiolitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study evaluated the efficacy and safety of 3% nebulized hypertonic saline (NHS) in infants with acute bronchiolitis (AB). METHODS: We systematically searched the PUBMED, EMBASE, Cochrane Library, China National Knowledge Infrastructure Database, WANFANG, and VIP databases from inception to June 1, 2022. We included randomized controlled trials comparing NHS with 0.9% saline. Outcomes included the length of hospital stay (LOS), rate of hospitalization (ROH), clinical severity score (CSS), rate of readmission, respiratory distress assessment instrument, and adverse events. RevMan V5.4 software was used for statistical analysis. RESULTS: A total of 27 trials involving 3495 infants were included in this study. Compared to normal saline, infants received 3% NHS showed better outcomes in LOS reduction (MD = -0.60, 95% CI [-1.04, -0.17], I2 = 92%, P = .007), ROH decrease (OR = 0.74, 95% CI [0.59, 0.91], I2 = 0%, P = .005), CSS improvement at day 1 (MD = -0.79, 95% CI [-1.23, -0.34], I2 = 74%, P < .001), day 2 (MD = -1.26, 95% CI [-2.02, -0.49], I2 = 91%, P = .001), and day 3 and over (MD = -1.27, 95% CI [-1.92, -0.61], I2 = 79%, P < .001), and respiratory distress assessment instrument enhancement (MD = -0.60, 95% CI [-0.95, -0.26], I2 = 0%, P < .001). No significant adverse events related to 3% NHS were observed. CONCLUSION: This study showed that 3% NHS was better than 0.9% normal saline in reducing LOS, decreasing ROH, improving CSS, and in enhancing the severity of respiratory distress. Further studies are needed to validate these findings.

FgLEU1 Is Involved in Leucine Biosynthesis, Sexual Reproduction, and Full Virulence in Fusarium graminearum.

Fusarium head blight (FHB) caused by Fusarium graminearum is a significant disease among cereal crops. In F. graminearum, biosynthesis of leucine, which is a branched chain amino acid, is achieved by converting α-isopropylmalate to ß-isopropylmalate catalyzed by isopropylmalate isomerase encoded by LEU1. Considering the potential for targeting this pathway by fungicides, we characterized the gene FgLEU1 (FGSG-09589) in the Fusarium graminearum genome using bioinformatics methods. For functional characterization, we constructed a deletion mutant of FgLEU1 (ΔLEU1) through homologous recombination. Compared with the wild-type strain PH-1, ΔLEU1 showed slower colony growth and fewer aerial mycelia. Leucine addition was needed to ensure proper mutant growth. Further, ΔLEU1 showed decreased conidial production and germination rates, and could not produce ascospores. Moreover, ΔLEU1 showed complete loss of pathogenicity and reduced ability to produce deoxynivalenol (DON) and aurofusarin. Upstream and downstream genes of FgLEU1 were significantly upregulated in ΔLEU1. Contrary to previous reports, the deletion mutant was more resistant to osmotic stress and cell wall-damaging agents than the wild-type. Taken together, FgLEU1 plays a crucial role in leucine synthesis, aerial mycelial growth, sexual and asexual reproduction, pathogenicity, virulence, and pigmentation in Fusarium graminearum, indicating its potential as a target for novel antifungal agents.

Peroxisome Proliferator FpPEX11 Is Involved in the Development and Pathogenicity in Fusarium pseudograminearum.

Fusarium crown rot (FCR) of wheat, an important soil-borne disease, presents a worsening trend year by year, posing a significant threat to wheat production. Fusarium pseudograminearum cv. b was reported to be the dominant pathogen of FCR in China. Peroxisomes are single-membrane organelles in eukaryotes that are involved in many important biochemical metabolic processes, including fatty acid ß-oxidation. PEX11 is important proteins in peroxisome proliferation, while less is known in the fungus F. pseudograminearum. The functions of FpPEX11a, FpPEX11b, and FpPEX11c in F. pseudograminearum were studied using reverse genetics, and the results showed that FpPEX11a and FpPEX11b are involved in the regulation of vegetative growth and asexual reproduction. After deleting FpPEX11a and FpPEX11b, cell wall integrity was impaired, cellular metabolism processes including active oxygen metabolism and fatty acid ß-oxidation were significantly blocked, and the production ability of deoxynivalenol (DON) decreased. In addition, the deletion of genes of FpPEX11a and FpPEX11b revealed a strongly decreased expression level of peroxisome-proliferation-associated genes and DON-synthesis-related genes. However, deletion of FpPEX11c did not significantly affect these metabolic processes. Deletion of the three protein-coding genes resulted in reduced pathogenicity of F. pseudograminearum. In summary, FpPEX11a and FpPEX11b play crucial roles in the growth and development, asexual reproduction, pathogenicity, active oxygen accumulation, and fatty acid utilization in F. pseudograminearum.

Mitochondrial Porin Is Involved in Development, Virulence, and Autophagy in Fusarium graminearum.

Mitochondrial porin, the voltage-dependent anion-selective channel (VDAC), is the most abundant protein in the outer membrane, and is critical for the exchange of metabolites and phospholipids in yeast and mammals. However, the functions of porin in phytopathogenic fungi are not known. In this study, we characterized a yeast porin orthologue, Fgporin, in Fusarium graminearum. The deletion of Fgporin resulted in defects in hyphal growth, conidiation, and perithecia development. The Fgporin deletion mutant showed reduced virulence, deoxynivalenol production, and lipid droplet accumulation. In addition, the Fgporin deletion mutant exhibited morphological changes and the dysfunction of mitochondria, and also displayed impaired autophagy in the non-nitrogen medium compared to the wild type. Yeast two-hybrid and bimolecular fluorescence complementation assays indicated that Fgporin interacted with FgUps1/2, but not with FgMdm35. Taken together, these results suggest that Fgporin is involved in hyphal growth, asexual and sexual reproduction, virulence, and autophagy in F. graminearum.

Indole-Based Long-Wavelength Fluorescent Probes for Bioimaging of S-Nitrosylation in Mitochondria.

S-Nitrosylation has been found to play an important role in regulating mitochondrial function. However, probes for detection of protein S-nitrosylation in mitochondria remain unexplored. Herein, a novel 4-(pyridin-4-yl)vinyl-substituted indole was designed, exhibiting a long-wavelength emission and a high fluorescent quantum yield. Functionalization of the 7-position of the indole ring with an arylphosphine ester resulted with probes with efficient mitochondria-targeting ability. Furthermore, the indole-arylphosphine displayed a significant fluorescence enhancement upon exposure to S-nitrosoglutathione (GSNO) at low micromolar concentrations in A431 cells. Taken together, this study provides a new indole-based fluorescent probe with a unique long-wavelength emission for direct detection of S-nitrosylation in mitochondria, which may represent a powerful tool for understanding the critical roles of S-nitrosylation within mitochondria of living organisms.

Erratum: Effect of local application of biphosphonates on improving peri-implant osseointegration in type-2 diabetic osteoporosis.

[This corrects the article on p. 5417 in vol. 11, PMID: 31632520.].

Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers.

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation and migration. The overexpression of the HER family has been recognized as one of the most common cellular dysregulation associated with a wide variety of tumor types. Antibody-drug conjugates (ADCs) represent a new and promising class of anticancer therapeutics that combine the cancer specificity of antibodies with cytotoxicity of chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) and trastuzumab-deruxtecan (DS-8201a), have been approved for HER2-positive metastatic breast cancer by the U.S. Food and Drug Administration (FDA) in 2013 and 2019, respectively. A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. A total of 11 ADCs that target HER family receptors (EGFR, HER2 or HER3) are currently under clinical trials. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.