Integrating convolution and self-attention improves language model of human genome for interpreting non-coding regions at base-resolution.

Interpretation of non-coding genome remains an unsolved challenge in human genetics due to impracticality of exhaustively annotating biochemically active elements in all conditions. Deep learning based computational approaches emerge recently to help interpret non-coding regions. Here, we present LOGO (Language of Genome), a self-attention based contextualized pre-trained language model containing only two self-attention layers with 1 million parameters as a substantially light architecture that applies self-supervision techniques to learn bidirectional representations of the unlabelled human reference genome. LOGO is then fine-tuned for sequence labelling task, and further extended to variant prioritization task via a special input encoding scheme of alternative alleles followed by adding a convolutional module. Experiments show that LOGO achieves 15% absolute improvement for promoter identification and up to 4.5% absolute improvement for enhancer-promoter interaction prediction. LOGO exhibits state-of-the-art multi-task predictive power on thousands of chromatin features with only 3% parameterization benchmarking against the fully supervised model, DeepSEA and 1% parameterization against a recent BERT-based DNA language model. For allelic-effect prediction, locality introduced by one dimensional convolution shows improved sensitivity and specificity for prioritizing non-coding variants associated with human diseases. In addition, we apply LOGO to interpret type 2 diabetes (T2D) GWAS signals and infer underlying regulatory mechanisms. We make a conceptual analogy between natural language and human genome and demonstrate LOGO is an accurate, fast, scalable, and robust framework to interpret non-coding regions for global sequence labeling as well as for variant prioritization at base-resolution.

Peroxisome-Mediated Reactive Oxygen Species Signals Modulate Programmed Cell Death in Plants.

Peroxisomes are a class of simple organelles that play an important role in plant reactive oxygen species (ROS) metabolism. Experimental evidence reveals the involvement of ROS in programmed cell death (PCD) in plants. Plant PCD is crucial for the regulation of plant growth, development and environmental stress resistance. However, it is unclear whether the ROS originated from peroxisomes participated in cellular PCD. Enzymes involved in the peroxisomal ROS metabolic pathways are key mediators to figure out the relationship between peroxisome-derived ROS and PCD. Here, we summarize the peroxisomal ROS generation and scavenging pathways and explain how peroxisome-derived ROS participate in PCD based on recent progress in the functional study of enzymes related to peroxisomal ROS generation or scavenging. We aimed to elucidate the role of the peroxisomal ROS regulatory system in cellular PCD to show its potential in terms of accurate PCD regulation, which contribute to environmental stress resistance.

microRNAs: Key Players in Plant Response to Metal Toxicity.

Environmental metal pollution is a common problem threatening sustainable and safe crop production. Heavy metals (HMs) cause toxicity by targeting key molecules and life processes in plant cells. Plants counteract excess metals in the environment by enhancing defense responses, such as metal chelation, isolation to vacuoles, regulating metal intake through transporters, and strengthening antioxidant mechanisms. In recent years, microRNAs (miRNAs), as a small non-coding RNA, have become the central regulator of a variety of abiotic stresses, including HMs. With the introduction of the latest technologies such as next-generation sequencing (NGS), more and more miRNAs have been widely recognized in several plants due to their diverse roles. Metal-regulated miRNAs and their target genes are part of a complex regulatory network. Known miRNAs coordinate plant responses to metal stress through antioxidant functions, root growth, hormone signals, transcription factors (TF), and metal transporters. This article reviews the research progress of miRNAs in the stress response of plants to the accumulation of HMs, such as Cu, Cd, Hg, Cr, and Al, and the toxicity of heavy metal ions.

A Nck-associated protein 1-like protein affects drought sensitivity by its involvement in leaf epidermal development and stomatal closure in rice.

Water deficit is a major environmental threat affecting crop yields worldwide. In this study, a drought stress-sensitive mutant drought sensitive 8 (ds8) was identified in rice (Oryza sativa L.). The DS8 gene was cloned using a map-based approach. Further analysis revealed that DS8 encoded a Nck-associated protein 1 (NAP1)-like protein, a component of the SCAR/WAVE complex, which played a vital role in actin filament nucleation activity. The mutant exhibited changes in leaf cuticle development. Functional analysis revealed that the mutation of DS8 increased stomatal density and impaired stomatal closure activity. The distorted actin filaments in the mutant led to a defect in abscisic acid (ABA)-mediated stomatal closure and increased ABA accumulation. All these resulted in excessive water loss in ds8 leaves. Notably, antisense transgenic lines also exhibited increased drought sensitivity, along with impaired stomatal closure and elevated ABA levels. These findings suggest that DS8 affects drought sensitivity by influencing actin filament activity.

Using Heading date 1 preponderant alleles from indica cultivars to breed high-yield, high-quality japonica rice varieties for cultivation in south China.

Heading date 1 (Hd1) is an important gene for the regulation of flowering in rice, but its variation in major cultivated rice varieties, and the effect of this variation on yield and quality, remains unknown. In this study, we selected 123 major rice varieties cultivated in China from 1936 to 2009 to analyse the relationship between the Hd1 alleles and yield-related traits. Among these varieties, 19 haplotypes were detected in Hd1, including two major haplotypes (H8 and H13) in the japonica group and three major haplotypes (H14, H15 and H16) in the indica group. Analysis of allele frequencies showed that the secondary branch number was the major aimed for Chinese indica breeding. In the five major haplotypes, SNP316 (C-T) was the only difference between the two major japonica haplotypes, and SNP495 (C-G) and SNP614 (G-A) are the major SNPs in the three indica haplotypes. Association analysis showed that H16 is the most preponderant allele in modern cultivated Chinese indica varieties. Backcrossing this allele into the japonica variety Chunjiang06 improved yield without decreasing grain quality. Therefore, our analysis offers a new strategy for utilizing these preponderant alleles to improve yield and quality of japonica varieties for cultivation in the southern areas of China.

Transcriptional programs of infectious spleen and kidney necrosis virus (ISKNV) in vitro and in vivo.

Infectious spleen and kidney necrosis virus (ISKNV), causing serious infectious diseases to marine and freshwater fishes, is the type species of the genus Megalocytivirus, family Iridoviridae. In this study, the transcriptional programs of ISKNV in vitro (MFF-1 cells) and in vivo (spleens from mandarin fish) were investigated using real-time PCR. Transcription of all the putative open reading frames (ORFs) of ISKNV was verified. The temporal expression patterns of ISKNV ORFs in vitro and in vivo, including peak expression times (PETs) and relative maximal expression levels, were determined and compared. The K-means clustering with Spearman rank correlation was generated in heat maps constructed based on ISKNV ORF expression profiles in vivo and in vitro. The current study may provide a global picture of ISKNV infection at the transcription level and help better understand the molecular pathogenic mechanism of megalocytiviruses.

PALE-GREEN LEAF12 Encodes a Novel Pentatricopeptide Repeat Protein Required for Chloroplast Development and 16S rRNA Processing in Rice.

Pentatricopeptide repeat (PPR) proteins regulate organellar gene expression in plants, through their involvement in organellar RNA metabolism. In rice (Oryza sativa), 477 genes are predicted to encode PPR proteins; however, the majority of their functions remain unknown. In this study, we identified and characterized a rice mutant, pale-green leaf12 (pgl12); at the seedling stage, pgl12 mutants had yellow-green leaves, which gradually turned pale green as the plants grew. The pgl12 mutant had significantly reduced Chl contents and increased sensitivity to changes in temperature. A genetic analysis revealed that the pgl12 mutation is recessive and located within a single nuclear gene. Map-based cloning of PGL12, including a transgenic complementation test, confirmed the presence of a base substitution (C to T), generating a stop codon, within LOC_Os12g10184 in the pgl12 mutant. LOC_Os12g10184 encodes a novel PLS-type PPR protein containing 17 PPR motifs and targeted to the chloroplasts. A quantitative real-time PCR analysis showed that PGL12 was expressed in various tissues, especially the leaves. We also showed that the transcript levels of several nuclear- and plastid-encoded genes associated with chloroplast development and photosynthesis were significantly altered in pgl12 mutants. The mutant exhibited defects in the 16S rRNA processing and splicing of the plastid transcript ndhA. Our results indicate that PGL12 is a new PLS-type PPR protein required for proper chloroplast development and 16S rRNA processing in rice.

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence.

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 (del1). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes.

EARLY SENESCENCE1 Encodes a SCAR-LIKE PROTEIN2 That Affects Water Loss in Rice.

The global problem of drought threatens agricultural production and constrains the development of sustainable agricultural practices. In plants, excessive water loss causes drought stress and induces early senescence. In this study, we isolated a rice (Oryza sativa) mutant, designated as early senescence1 (es1), which exhibits early leaf senescence. The es1-1 leaves undergo water loss at the seedling stage (as reflected by whitening of the leaf margin and wilting) and display early senescence at the three-leaf stage. We used map-based cloning to identify ES1, which encodes a SCAR-LIKE PROTEIN2, a component of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein family verprolin-homologous complex involved in actin polymerization and function. The es1-1 mutants exhibited significantly higher stomatal density. This resulted in excessive water loss and accelerated water flow in es1-1, also enhancing the water absorption capacity of the roots and the water transport capacity of the stems as well as promoting the in vivo enrichment of metal ions cotransported with water. The expression of ES1 is higher in the leaves and leaf sheaths than in other tissues, consistent with its role in controlling water loss from leaves. GREEN FLUORESCENT PROTEIN-ES1 fusion proteins were ubiquitously distributed in the cytoplasm of plant cells. Collectively, our data suggest that ES1 is important for regulating water loss in rice.

PGL, encoding chlorophyllide a oxygenase 1, impacts leaf senescence and indirectly affects grain yield and quality in rice.

Chlorophyll (Chl) b is a ubiquitous accessory pigment in land plants, green algae, and prochlorophytes. This pigment is synthesized from Chl a by chlorophyllide a oxygenase and plays a key role in adaptation to various environments. This study characterizes a rice mutant, pale green leaf (pgl), and isolates the gene PGL by using a map-based cloning approach. PGL, encoding chlorophyllide a oxygenase 1, is mainly expressed in the chlorenchyma and activated in the light-dependent Chl synthesis process. Compared with wild-type plants, pgl exhibits a lower Chl content with a reduced and disorderly thylakoid ultrastructure, which decreases the photosynthesis rate and results in reduced grain yield and quality. In addition, pgl exhibits premature senescence in both natural and dark-induced conditions and more severe Chl degradation and reactive oxygen species accumulation than does the wild-type. Moreover, pgl is sensitive to heat stress.

Quantitative trait loci identification, fine mapping and gene expression profiling for ovicidal response to whitebacked planthopper (Sogatella furcifera Horvath) in rice (Oryza sativa L.).

BACKGROUND: The whitebacked planthopper (WBPH), Sogatella furcifera Horváth, is a serious rice pest in Asia. Ovicidal resistance is a natural rice defense mechanism against WBPH and is characterized by the formation of watery lesions (WLs) and increased egg mortality (EM) at the WBPH oviposition sites. RESULTS: This study aimed to understand the genetic and molecular basis of rice ovicidal resistance to WBPH by combining genetic and genomic analyses. First, the ovicidal trait in doubled haploid rice lines derived from a WBPH-resistant cultivar (CJ06) and a WBPH-susceptible cultivar (TN1) were phenotyped based on the necrotic symptoms of the leaf sheaths and EM. Using a constructed molecular linkage map, 19 quantitative trait loci (QTLs) associated with WLs and EM were identified on eight chromosomes. Of them, qWL6 was determined to be a major QTL for WL. Based on chromosome segment substitution lines and a residual heterozygous population, a high-resolution linkage analysis further defined the qWL6 locus to a 122-kb region on chromosome 6, which was annotated to encode 20 candidate genes. We then conducted an Affymetrix microarray analysis to determine the transcript abundance in the CJ06 and TN1 plants. Upon WBPH infestation, 432 genes in CJ06 and 257 genes in TN1 were significantly up-regulated, while 802 genes in CJ06 and 398 genes in TN1 were significantly down-regulated. This suggests that remarkable global changes in gene expression contribute to the ovicidal resistance of rice. Notably, four genes in the 122-kb region of the qWL6 locus were differentially regulated between CJ06 and TN1 in response to the WBPH infestation, suggesting they may be candidate resistance genes. CONCLUSIONS: The information obtained from the fine mapping of qWL6 and the microarray analyses will facilitate the isolation of this important resistance gene and its use in breeding WBPH-resistant rice.

Evaluation of novel promoters for vascular tissue-specific gene expression in Populus.

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.

Comparative analysis of PLATZ transcription factors in six poplar species and analysis of the role of PtrPLATZ14 in leaf development.

Plant AT-rich sequence and zinc-binding (PLATZ) proteins are a class of plant-specific transcription factor that play a crucial role in plant growth, development, and stress response. However, the evolutionary relationship of the PLATZ gene family across the Populus genus and the biological functions of the PLATZ protein require further investigation. In this study, we identified 133 PLATZ genes from six Populus species belonging to four Populus sections. Synteny analysis of the PLATZ gene family indicated that whole genome duplication events contributed to the expansion of the PLATZ family. Among the nine paralogous pairs, the protein structure of PtrPLATZ14/18 pair exhibited significant differences with others. Through gene expression patterns and co-expression networks, we discovered divergent expression patterns and sub-networks, and found that the members of pair PtrPLATZ14/18 might play different roles in the regulation of macromolecule biosynthesis and modification. Furthermore, we found that PtrPLATZ14 regulates poplar leaf development by affecting cell size control genes PtrGRF/GIF and PtrTCP. In conclusion, our study provides a theoretical foundation for exploring the evolution relationships and functions of the PLATZ gene family within Populus species and provides insights into the function and potential mechanism of PtrPLATZ14 in leaf morphology that were diverse across the Populus genus.

PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa.

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

Magnetic resonance-guided focused ultrasound for essential tremor: a prospective, single center, single-arm study.

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

CCNet: Criss-Cross Attention for Semantic Segmentation.

Contextual information is vital in visual understanding problems, such as semantic segmentation and object detection. We propose a criss-cross network (CCNet) for obtaining full-image contextual information in a very effective and efficient way. Concretely, for each pixel, a novel criss-cross attention module harvests the contextual information of all the pixels on its criss-cross path. By taking a further recurrent operation, each pixel can finally capture the full-image dependencies. Besides, a category consistent loss is proposed to enforce the criss-cross attention module to produce more discriminative features. Overall, CCNet is with the following merits: 1) GPU memory friendly. Compared with the non-local block, the proposed recurrent criss-cross attention module requires 11× less GPU memory usage. 2) High computational efficiency. The recurrent criss-cross attention significantly reduces FLOPs by about 85 percent of the non-local block. 3) The state-of-the-art performance. We conduct extensive experiments on semantic segmentation benchmarks including Cityscapes, ADE20K, human parsing benchmark LIP, instance segmentation benchmark COCO, video segmentation benchmark CamVid. In particular, our CCNet achieves the mIoU scores of 81.9, 45.76 and 55.47 percent on the Cityscapes test set, the ADE20K validation set and the LIP validation set respectively, which are the new state-of-the-art results. The source codes are available at https://github.com/speedinghzl/CCNethttps://github.com/speedinghzl/CCNet.

Inequality Measure of Leaf Area Distribution for a Drought-Tolerant Landscape Plant.

Measuring the inequality of leaf area distribution per plant (ILAD) can provide a useful tool for quantifying the influences of intra- and interspecific competition, foraging behavior of herbivores, and environmental stress on plants' above-ground architectural structures and survival strategies. Despite its importance, there has been limited research on this issue. This paper aims to fill this gap by comparing four inequality indices to measure ILAD, using indices for quantifying household income that are commonly used in economics, including the Gini index (which is based on the Lorenz curve), the coefficient of variation, the Theil index, and the mean log deviation index. We measured the area of all leaves for 240 individual plants of the species Shibataea chinensis Nakai, a drought-tolerant landscape plant found in southern China. A three-parameter performance equation was fitted to observations of the cumulative proportion of leaf area vs. the cumulative proportion of leaves per plant to calculate the Gini index for each individual specimen of S. chinensis. The performance equation was demonstrated to be valid in describing the rotated and right shifted Lorenz curve, given that >96% of root-mean-square error values were smaller than 0.004 for 240 individual plants. By examining the correlation between any of the six possible pairs of indices among the Gini index, the coefficient of variation, the Theil index, and the mean log deviation index, the data show that these indices are closely related and can be used interchangeably to quantify ILAD.

VP23R of infectious spleen and kidney necrosis virus mediates formation of virus-mock basement membrane to provide attaching sites for lymphatic endothelial cells.

Putative open reading frames (ORFs) encoding laminin-like proteins are found in all members of the genus Megalocytivirus, family Iridoviridae. This is the first study that identified the VP23R protein encoded by ORF23R of the infectious spleen and kidney necrosis virus (ISKNV), a member of these genes of megalocytiviruses. The VP23R mRNA covering the ISKNV genomic coordinates 19547 to 22273 was transcribed ahead of the major capsid protein. Immunofluorescence analysis demonstrated that VP23R was expressed on the plasma membrane of the ISKNV-infected cells and could not be a viral envelope protein. Residues 292 to 576 of VP23R are homologous to the laminin γ1III2-6 fragment, which covers the nidogen-binding site. An immunoprecipitation assay showed that VP23R could interact with nidogen-1, and immunohistochemistry showed that nidogen-1 was localized on the outer membrane of the infected cells. Electron microscopy showed that a virus-mock basement membrane (VMBM) was formed on the surface of the infected cells and a layer of endothelial cells (ECs) was attached to the VMBM. The VMBM contained VP23R and nidogen-1 but not collagen IV. The attached ECs were identified as lymphatic endothelial cells (LECs), which have unique feature of overlapping intercellular junctions and can be stained by immunohistochemistry using an antibody against a specific lymphatic marker, Prox-1. Such infection signs have never been described in viruses. Elucidating the functions of LECs attached to the surface of the infected cells may be useful for studies on the pathogenic mechanisms of megalocytiviruses and may also be important for studies on lymphangiogenesis and basement membrane functions.

VP15R from infectious spleen and kidney necrosis virus is a non-muscle myosin-II-binding protein.

VP15R protein, encoded by the 15th open reading frame of infectious spleen and kidney necrosis virus (ISKNV), was identified. VP15R is a 263-residue protein that is first transcribed within 12 h post-infection. The VP15R mRNA is transcribed beginning at ISKNV genomic coordinate 12111, extending 167 bp upstream of the initiation codon. No signal peptides, transmembrane fragments, or nuclear localization signal sequences were predicted in the VP15R sequence. The 102-202 sequence of VP15R is homologous to the 1153-1253 sequence of the filamin C protein of Danio rerio (zebrafish), with an identity of 29%. Immunofluorescence and VP15R-GFP fusion protein subcellular localization assays showed that VP15R is localized in the cytoplasm. Pull-down and MALDI-TOF-TOF/MS assays demonstrated that VP15R can bind to the non-muscle myosin II (NM II) protein. Co-immunoprecipitation assays confirmed that VP15R can bind to the heavy chains of the NM II protein of mandarin fish, mice, and humans.

The Zap-X Radiosurgical System in the Treatment of Intracranial Tumors: A Technical Case Report.

BACKGROUND AND IMPORTANCE: The Zap-X system (Zap Surgical Systems Inc, San Carlos, California) is a radically new surgical robot designed for brain and head and neck radiosurgery. It represents the first new dedicated brain stereotactic radiosurgery platform in almost half a century optimizing the goals of safety, speed, and accuracy. The Zap-X system was used in a required Chinese National Medical Products Administration clinical study. In early January 2020, 2 patients were treated with the Zap-X robot prior to a national COVID-19 lockdown. Both were closely followed via clinical exam and magnetic resonance imaging (MRI) imaging. Prospectively collected data were used to generate this report. CLINICAL PRESENTATION: Two female patients, each harboring either a trigeminal schwannoma or petroclival meningioma, were treated with the Zap-X robot. Respective tumor volumes were 2.60 and 4.02 cm3. A radiation dose of 13 Gy was prescribed to the 50% isodose line. At 8 mo of follow-up, preoperative symptoms were either resolved or stable and MRI imaging demonstrated a 31% and 56% reduction in lesion volume, respectively. In both patients, symptoms improved, and tumor volumes decreased, whereas no major complication was observed. CONCLUSION: Given only 2 patients and short-term follow-up, any conclusions about the safety and efficacy of the Zap-X radiosurgery robot are preliminary. However, in the absence of any other published outcomes to date, this small case series may be of interest to many radiosurgical specialists.