Hybrid fragment-SMILES tokenization for ADMET prediction in drug discovery.

BACKGROUND: Drug discovery and development is the extremely costly and time-consuming process of identifying new molecules that can interact with a biomarker target to interrupt the disease pathway of interest. In addition to binding the target, a drug candidate needs to satisfy multiple properties affecting absorption, distribution, metabolism, excretion, and toxicity (ADMET). Artificial intelligence approaches provide an opportunity to improve each step of the drug discovery and development process, in which the first question faced by us is how a molecule can be informatively represented such that the in-silico solutions are optimized. RESULTS: This study introduces a novel hybrid SMILES-fragment tokenization method, coupled with two pre-training strategies, utilizing a Transformer-based model. We investigate the efficacy of hybrid tokenization in improving the performance of ADMET prediction tasks. Our approach leverages MTL-BERT, an encoder-only Transformer model that achieves state-of-the-art ADMET predictions, and contrasts the standard SMILES tokenization with our hybrid method across a spectrum of fragment library cutoffs. CONCLUSION: The findings reveal that while an excess of fragments can impede performance, using hybrid tokenization with high frequency fragments enhances results beyond the base SMILES tokenization. This advancement underscores the potential of integrating fragment- and character-level molecular features within the training of Transformer models for ADMET property prediction.

Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.

The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

Monitoring of the disulfide scrambled species by mixed-mode SEC-HPLC during the purification of a bispecific antibody.

Size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC) is an analytical method routinely used for assessing aggregation content in protein samples. As SEC-HPLC separates analytes based on their hydrodynamic radius, it generally lacks the capability of differentiating species that are similar in size. Recently while purifying a bispecific antibody (bsAb), we noticed that SEC-HPLC can provide certain degree of resolution between the target bsAb and a disulfide scrambled form, although these two species were identical in molecular weight. In seeing the unexpected potential of SEC-HPLC at resolving species with similar size, we further tested Zenix SEC-300, a mixed-mode SEC-HPLC column from Sepax, which was reported to be capable of separating protein analytes based on other factors besides size. The Zenix column indeed provided resolution much better than the regular SEC-HPLC column. Upon further optimization, the Zenix column allowed close to baseline separation of the correctly folded and the disulfide scrambled species. The current study, as a complement to the previous reports, further demonstrates that mix-mode SEC-HPLC is capable of separating protein analytes that are close in size but are different in conformation and/or surface characteristics.

Diaphragm dysfunction is found in patients with chronic painful temporomandibular disorder: A case-control study.

Aim: To determine whether patients with chronic painful temporomandibular disorder (TMD) had abnormal diaphragm function compared to healthy controls and to explore the correlation between diaphragm contractility, psychological status, and pain characteristics. Methods: A single-blinded, case-control study was conducted involving 23 chronic painful TMD patients and 22 healthy volunteers. The examination and diagnosis were performed according to the Diagnostic Criteria for Temporomandibular Disorders, and questionnaires were used to evaluate pain, depression, anxiety, and physical symptoms status. B-mode ultrasound was used to measure diaphragm thickness and contractility. The sonographer responsible for measuring the diaphragm was blinded to group membership. Results: 1. Depression, anxiety, and physical symptoms scores were significantly higher in the patients than in the controls (p < 0.05). 2. The Interference Score of pain was significantly correlated with depression and physical symptoms (p < 0.01). 3. Bilateral diaphragm contractility was significantly smaller in the patients than in the controls (right: P = 0.003; left: P = 0.001). 3. There was no correlation between diaphragm contractility on the left and right sides in the patients (r = -0.112, P = 0.611), while there was a positive correlation in the control group (r = 0.638, P = 0.001). 4. No correlation was found between the degree of diaphragm contractility, psychological status, and pain scores. Conclusions: 1. Patients with chronic painful TMD have worse psychological status, including depression, anxiety, and physical symptoms. 2. Patients with chronic painful TMD have a smaller degree of bilateral diaphragm contractility and more significant left-right incongruity, which indicated that diaphragm dysfunction may be correlated with chronic painful temporomandibular disorder.

Transcriptomics analyses reveal the key genes involved in stamen petaloid formation in Alcea rosea L.

Alcea rosea L. is a traditional flower with a long cultivation history. It is extensively cultivated in China and is widely planted in green belt parks or used as cut flowers and potted ornamental because of its rich colors and flower shapes. Double-petal A. rosea flowers have a higher aesthetic value compared to single-petal flowers, a phenomenon determined by stamen petaloid. However, the underlying molecular mechanism of this phenomenon is still very unclear. In this study, an RNA-based comparative transcriptomic analysis was performed between the normal petal and stamen petaloid petal of A. rosea. A total of 3,212 differential expressed genes (DEGs), including 2,620 up-regulated DEGs and 592 down-regulated DEGs, were identified from 206,188 unigenes. Numerous DEGs associated with stamen petaloid were identified through GO and KEGG enrichment analysis. Notably, there were 63 DEGs involved in the plant hormone synthesis and signal transduction, including auxin, cytokinin, gibberellin, abscisic acid, ethylene, brassinosteroid, jasmonic acid, and salicylic acid signaling pathway and 56 key transcription factors (TFs), such as MADS-box, bHLH, GRAS, and HSF. The identification of these DEGs provides an important clue for studying the regulation pathway and mechanism of stamen petaloid formation in A. rosea and provides valuable information for molecular plant breeding.

Integrating transformers and many-objective optimization for drug design.

BACKGROUND: Drug design is a challenging and important task that requires the generation of novel and effective molecules that can bind to specific protein targets. Artificial intelligence algorithms have recently showed promising potential to expedite the drug design process. However, existing methods adopt multi-objective approaches which limits the number of objectives. RESULTS: In this paper, we expand this thread of research from the many-objective perspective, by proposing a novel framework that integrates a latent Transformer-based model for molecular generation, with a drug design system that incorporates absorption, distribution, metabolism, excretion, and toxicity prediction, molecular docking, and many-objective metaheuristics. We compared the performance of two latent Transformer models (ReLSO and FragNet) on a molecular generation task and show that ReLSO outperforms FragNet in terms of reconstruction and latent space organization. We then explored six different many-objective metaheuristics based on evolutionary algorithms and particle swarm optimization on a drug design task involving potential drug candidates to human lysophosphatidic acid receptor 1, a cancer-related protein target. CONCLUSION: We show that multi-objective evolutionary algorithm based on dominance and decomposition performs the best in terms of finding molecules that satisfy many objectives, such as high binding affinity and low toxicity, and high drug-likeness. Our framework demonstrates the potential of combining Transformers and many-objective computational intelligence for drug design.

Heterogeneous Multi-Phase Grains Improving the Strength-Ductility Balance in Warm-Rolled Fe-18Mn-3Ti Steel.

The thermal properties, microstructure, and mechanical properties of Fe-18Mn-3Ti (wt%) were investigated, focusing on the effects of different heat-treatment processes. Results revealed that the 450 °C warm-rolling sample (450 WR) exhibited promising mechanical properties. Specifically, this sample displayed a yield strength of 988 MPa, an ultimate tensile strength of 1052 MPa, and total elongation of 15.49%. Consequently, a favorable strength-ductility balance was achieved. The strain-hardening ability surpassed that of the cold rolling sample (CR). Microstructure analysis indicated the simultaneous occurrence of dynamic equilibrium between grain deformation and re-crystallization because of the co-influence of thermal and strain in the warm rolling process. This desirable mechanical property was attributed to the presence of a multi-phase (α-martensite, austenite, and ε-martensite) and heterogeneous microstructure. The improvement of ultimate tensile strength was based on grain refinement, grain co-deformation, and the transformation-induced plasticity (TRIP) effect in the early stage of plastic deformation (stage Ⅰ). The improvement of ultimate elongation (TEL) was ascribed to the TRIP effect in the middle stage of plastic deformation (stage Ⅱ).

Characterization of a novel antioxidant byssal protein from Mytilus coruscus foot.

Mussel byssal proteins are of biomimetic importance for the development of novel underwater bio-adhesive agents. It is important to maintain a reduced state during the process of byssus adhesion. There are 19 mussel foot proteins (MFPs) have been reported in previous studies, among which only MFP-6 had been confirmed as an antioxidant protein in mussel byssus due to the function of cysteines, and playing an essential role in the redox balance of mussel byssus during adhesion process. Although the other four MFPs (MFP-16 ~ MFP-19) also have abundant cysteines, their function is still unknown. In this study, a novel mussel foot protein, named MFP-20, was identified from Mytilus coruscus foot. The sequential features, expression profile, and function of recombinant MFP-20 were verified. The results showed that MFP-20 has more abundant cysteines than other MFPs, the relative expression of mfp-20 was upregulated in Fe3+ stress and low pH seawater. In addition, different adhesive substrates induced significant changes of expression level of mfp-20. Furthermore, rMFP-20 showed strong antioxidant capacity in the DPPH assay, and the abundant cysteines in its sequence may play vital roles in the antioxidation activity. Our findings revealed the possible function of MFP-20 with a totally different sequence from the reported MFP-6 and provided new clues for exploring the redox balance of mussel byssus during the adhesion process.

CaptureSelect FcXP affinity medium exhibits strong aggregate separation capability.

Protein A affinity chromatography has been widely used for initial product capture in recombinant antibody/Fc-fusion purification. However, in general Protein A lacks the capability of separating aggregates (unless the aggregates are too large to enter the pores of resin beads or have their Protein A binding sites buried, in which case the aggregates do not bind). In the current work, we demonstrated that CaptureSelect FcXP affinity medium exhibited strong aggregate separation capability and effectively removed aggregates under pH or conductivity gradient elution in two bispecific antibody (bsAb) cases. For these two cases, aggregate contents were reduced from >16% and >22% (in the feed) to <1% and <5% (in the eluate) for the first and second bsAbs, respectively. While more case studies are required to further demonstrate FcXP's superiority in aggregate removal, findings from the current study suggest that FcXP can potentially be a better alternative than Protein A for product capture in cases where aggregate content is high.

Hedgehog signaling is required for larval muscle development and larval metamorphosis of the mussel Mytilus coruscus.

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.

Hyposalinity stress reduces mussel byssus secretion but does not cause detachment.

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.

Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection.

There has been an increase in the use of molecular probe diagnostic techniques for lung cancer, and magnetic resonance imaging (MRI) offers specific advantages for diagnosing pulmonary carcinoma. Furthermore, advancements in near-infrared II (NIR-II) fluorescence have provided a new method for precise intraoperative tumor resection. However, few probes combine preoperative diagnosis with intraoperative imaging. This study aims to fill this research void by employing a dual-modal probe that targets the epidermal growth factor receptor for MR and NIR-II imaging, enabling the preoperative diagnosis of lung cancer using MRI and precise intraoperative tumor localization using NIR-II with a single probe. The imaging effects and targeting ability of the probe were confirmed in cell lines, mouse models, and clinical samples. The MR signal decreased within 24 h in the patient-derived xenograft mouse model. The average signal-to-background ratio of NIR-II reached 3.98 ± 0.27. The clinical sample also showed a decrease in the T2 signal using MRI, and the NIR-II optical signal-to-background ratio was 3.29. It is expected that this probe can improve the diagnostic rate of lung cancer using MRI and enable precise intraoperative tumor resection using NIR-II.

Ammonia-induced oxidative stress triggered apoptosis in the razor clam (Sinonovacula constricta).

As one of the most significant contaminants and stressors in aquaculture systems, ammonia adversely jeopardizes the health of aquatic animals. Ammonia exposure affects the development, metabolism, and survival of shellfish. However, the responses of the innate immune and antioxidant systems and apoptosis in shellfish under ammonia stress have rarely been reported. In this study, razor clams (Sinonovacula constricta) were exposed to different concentrations of non-ion ammonia (0.25 mg/L, 2.5 mg/L) for 72 h and then placed in ammonia-free seawater for 72 h for recovery. The immune responses induced by ammonia stress on razor clams were investigated by antioxidant enzyme activities and degree of apoptosis in digestive gland and gill tissues at different time points. The results showed that exposure to a high concentration of ammonia greatly disrupted the antioxidant system of the razor clam by exacerbating the accumulation of reactive oxygen species ( O 2 - , H2O2) and disordering the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and the level of activity remained at a significantly high level after recovering for 72 h (P < 0.05). In addition, there were significant differences (P < 0.05) in the expression of key genes (Caspase 7, Cyt-c, Bcl-2, and Bax) in the mitochondrial apoptotic pathway in the digestive glands and gills of razor clams as a result of ammonia stress and were unable to return to normal levels after 72 h of recovery. TUNEL staining indicated that apoptosis was more pronounced in gills, showing a dose and time-dependent pattern. As to the results, ammonia exposure leads to the activation of innate immunity in razor clams, disrupts the antioxidant system, and activates the mitochondrial pathway of apoptosis. This is important for comprehending the mechanism underlying the aquatic toxicity resulting from ammonia in shellfish.

Unravelling the reason for different binding behaviors exhibited by antibody aggregates towards preparative and analytical Protein A columns.

We previously showed that the root cause of low Protein A step yield observed for certain antibodies/Fc-fusions is the presence of non-binding aggregates in cell culture harvest. A pre-assumption for the above conclusion is that the aggregates, while do not bind to the preparative Protein A column, can bind to the analytical Protein A-high performance liquid chromatography (HPLC) column used for titer measurement. In the current work, using materials from a previous case with the low yield issue, we confirmed that non-binding aggregates in preparative Protein A flow-through can indeed bind to the analytical Protein A column. In addition, we showed that this discrepancy is mainly due to the different loading densities applied under these two circumstances. We also demonstrated that aggregate bound to the analytical Protein A column slightly stronger than the monomer, as it exhibited a longer retention time. In summary, the current study not only confirmed that non-binding aggregates detected in the preparative Protein A flow-through bind to the Protein A-HPLC column and contribute to the measured titer of culture harvest but also unravelled the reason for different binding behaviors exhibited by antibody aggregates towards preparative and analytical Protein A columns.

NADK-mediated proline synthesis enhances high-salinity tolerance in the razor clam.

Euryhaline organisms can accumulate organic osmolytes to maintain osmotic balance between their internal and external environments. Proline is a pivotal organic small molecule and plays an important role in osmoregulation that enables marine shellfish to tolerate high-salinity conditions. During high-salinity challenge, NAD kinase (NADK) is involved in de novo synthesis of NADP(H) in living organisms, which serves as a reducing agent for the biosynthetic reactions. However, the role of shellfish NADK in proline biosynthesis remains elusive. In this study, we show the modulation of NADK on proline synthesis in the razor clam (Sinonovacula constricta) in response to osmotic stress. Under acute hypersaline conditions, gill tissues exhibited a significant increase in the expression of ScNADK. To elucidate the role of ScNADK in proline biosynthesis, we performed dsRNA interference in the expression of ScNADK in gill tissues to assess proline content and the expression levels of key enzyme genes involved in proline biosynthesis. The results indicate that the knock-down of ScNADK led to a significant decrease in proline content (P<0.01), as well as the expression levels of two proline synthetase genes P5CS and P5CR involved in the glutamate pathway. Razor clams preferred to use ornithine as substrate for proline synthesis when the glutamate pathway is blocked. Exogenous administration of proline greatly improved cell viability and mitigated cell apoptosis in gills. In conclusion, our results demonstrate the important role of ScNADK in augmenting proline production under high-salinity stress, by which the razor clam is able to accommodate salinity variations in the ecological niche.

First report of Phaeosphaeria caricicola causing leaf spot on Belamcanda chinensis in China.

Belamcanda chinensis (L.) Redouté, a member of the Iridaceae family, is globally well-known for its medicinal value as clearing away heat, detoxifying, detumescence and pain (Qin 2000). In 2021, spots were observed on 40% B. chinensis leaves and about 28 disease index in Wanzhou District (30°32'N; 108°22'E) of Chongqing. Initial symptoms appeared as circular yellow white, sunken spots lesions, and then expanded into irregular lesions, the center of the spots was beige, external layer was light brown and surrounded by yellow halo. Symptomatic leaf tissues (5 × 5 mm) were cut from the infected margin, surface sterilized with 75% ethanol for 1 min, washed with 3% sodium hypochlorite for 3 min, rinsed three times with sterile water, placed on potato dextrose agar (PDA) medium incubated at 25°C for 7 days in the dark, forty isolates with similar morphology were obtained. Three isolates (SG9、SG20 and SG33) was selected for subsequent research. Colonies color changed from beige to light brown color after 14 days on PDA medium. Fungal colonies transformed from beige to brown at the edges after 28 days and light brown on top. Ascomata dark brown, ellipsoidal to globose 116.6 to 253.3 × 89.6 to 172.6 µm in diamensions. Asci stipitate, cylindrical with obtuse ends, and 69.1 to 114.7 × 10.2 to 24.1 µm (n = 30) in size, with eight overlapping linearly biseriate ascospores. Ascospores brown, narrowly fusiform, straight or slightly curved with three transversely septate, slightly constricted at septa, and 9.7 to 12.6 × 27.6 to 32.6 µm (n = 30). These characteristics are consistent with Phaeosphaeria sp. reported by Quaedvlieg et al in 2013. DNA was extracted from representative isolates. The internal transcribed spacer (ITS) region, the large subunit rDNA (LSU), the small subunit rDNA (SSU) and the RNA polymerase II second largest subunit (RPB2) genes were amplified for Polymerase chain reaction (PCR) by used ITS1/ITS4, LR5/LROR, NS1/NS4, and RPB2-5f2/RPB2-7cr primers (White et al. 1990; Vilgalys et al. 1990; Qi M W. et al. 2008; De G. J. et al. 1992). The sequences were submitted to NCBI GenBank: SG-G9 (ITS, OR701701; LSU, OR701699; SSU, OR701700; RPB2, OR738464); SG-G20 (ITS, OQ748032; LSU, OQ780728; SSU, OQ780723; RPB2, OQ779979); SG-G33 (ITS, OQ748033; LSU, OQ780729; SSU, OQ780722; RPB2, OQ779980). A phylogenetic analysis revealed a 99% similarity to the Phaeosphaeria caricicola CBS 603.86 (ITS, KF251182; LSU, GQ387590; SSU, GQ387529; RPB2, KF252189) sequences. Mycelial agar plugs (5-mm diameter) from a 7-day-old PDA culture of a fungal isolate were placed onto pinpricked leaves of three two-year-old B. chinensis plants. While the sterile PDA plugs inoculated in pinpricked leaves of B. chinensis as controls. Inoculated plants were placed in a greenhouse at 25°C and remained 95±1% relative humidity. The inoculated leaves of treatment developed symptoms after 20 days, whereas no symptoms occurred on controls, fulfilling Koch's postulates. The experiments were repeated three times. The fungus was re-isolated and was identical to original isolate by morphologically and molecularly. As far as we know, P. caricicola can cause diseases on carex plants and has been found in Switzerland. This is the first report of P. caricicola causing leaf spot on B. chinensis in China. Along with recording the occurrence of this disease, plant disease management strategies need to be established to reduce losses.

Acidic pH or salt treatment can convert soluble antibody aggregates in culture harvest into monomers and improve Protein A chromatography step yield.

While purifying a regular monospecific antibody, we found that the Protein A step yield was much lower than expected. Further studies revealed that the antibody formed large-size aggregates that did not bind to the Protein A resin, hence leading to dropped recovery. In an attempt to solve this low yield issue, we found that mildly acidic pH or ammonium sulfate treatment can partially convert the aggregates into monomers. In addition, when acidic pH treated culture harvest was processed by Protein A chromatography, the yield was restored to the normal range, suggesting that the monomers recovered from aggregates regained Protein A binding capability. Thus, low pH treatment of culture harvest can be potentially used as a general approach for improving Protein A step yield in cases where non-binding antibody aggregates are formed through noncovalent interactions.

Flow-diverter stents in intracranial aneurysm treatment: impact on covered cerebral artery branches.

OBJECTIVE: Flow diverter stents (FDSs) have attracted interest for intracranial aneurysm (IA) treatment; however, occlusion of side branches and related complications have been reported. This study aimed to investigate the effects of FDSs in IA management when different branches of intracranial arteries are covered. MATERIALS AND METHODS: A cross-sectional study was conducted using PUBMED, Embase, Web of Science, and Cochrane databases to include randomized or nonrandomized comparative-designed studies from January 2000 to August 2022 which reported outcomes of occlusion/narrowing of branches after IA treatment using FDSs. The PRISMA guidelines were used for our report. A random-effects meta-analysis was conducted to pool the outcomes, which included incidence rates of occlusion/narrowing of FDS-covered branches, branch occlusion-related symptoms, obliteration of IAs, and ideal clinical outcomes (modified Rankin Scale score ≤2). RESULTS: The authors identified 57 studies involving 3789 patients with IA managed by FDSs covering different branches. During the median imaging follow-up at 12 months, the IA obliteration rate was satisfactory (>70%) when covering the ophthalmic artery (OA), posterior communicating artery (PComA), anterior choroidal artery (AChoA) or anterior cerebral artery (ACA), but not the middle cerebral artery-M2 segment (MCA-M2; 69.5%; 95% CI: 60.8-77.5%) and posterior inferior cerebellar artery (PICA; 59.1%, 13/22). The overall ideal clinical outcome was observed in 97.4% of patients (95% CI: 95.5-98.9%). Higher rates of occlusion/narrowing of branches were identified when FDSs covered the ACA (66.6%; 95% CI: 45.1-85.3%), PComA (44.3%; 95% CI: 34.2-54.6%), or MCA-M2 (39.2%; 95% CI: 24.5-54.7%); the risks were lower when covering the OA (11.8%; 95% CI: 8.8-15.1%), PICA (6.8%; 95% CI: 1.5-14.5%), and AchoA (0.5%; 95% CI: 0.0-2.9%). The risk of branch occlusion-related complications was low (incidence rate <5%) for each of the six evaluated branches. CONCLUSIONS: Acceptable outcomes were identified following treatment of IAs when FDSs were placed across each of the six studied cerebral arteries. Treatment decisions regarding FDS placement across branch arteries should be made with the risk of complications from branch occlusion in mind.