Efficient electrosynthesis of HO2- from air for sulfide control in sewers.

Electrochemically in-situ generation of oxygen and caustic soda is promising for sulfide management while suffers from scaling, poor inactivating capacity, hydrogen release and ammonia escape. In this study, the four-compartment electrochemical cell efficiently captured oxygen molecules from the air chamber to produce HO2- without generating toxic by-products. Meanwhile, the catalyst layer surface of PTFE/CB-GDE maintained a relatively balanced gas-liquid micro-environment, enabling the formation of enduring solid-liquid-gas interfaces for efficient HO2- electrosynthesis. A dramatic increase in HO2- generation rate from 453.3 mg L-1 h-1 to 575.4 mg L-1 h-1 was attained by advancement in operation parameters design (flow channels, electrolyte types, flow rates and circulation types). Stability testing resulted in the HO2- generation rate over 15 g L-1 and the current efficiency (CE) exceeding 85%, indicating a robust stable operational capacity. Furthermore, after 120 mg L-1 HO2- treatment, an increase of 11.1% in necrotic and apoptotic cells in the sewer biofilm was observed, higher than that achieved with the addition of NaOH, H2O2 method. The in-situ electrosynthesis strategy for HO2- represents a significance toward the practical implementation of sulfide abatement in sewers, holding the potential to treat various sulfide-containing wastewater.

Single missing molar with wide mesiodistal length restored using a single or double implant-supported crown: A self-controlled case report and 3D finite element analysis.

PURPOSE: Based on a self-controlled case, this study evaluated the finite element analysis (FEA) results of a single missing molar with wide mesiodistal length (MDL) restored by a single or double implant-supported crown. METHODS: A case of a missing bilateral mandibular first molar with wide MDL was restored using a single or double implant-supported crown. The implant survival and peri-implant bone were compared. FEA was conducted in coordination with the case using eight models with different MDLs (12, 13, 14, and 15 mm). Von Mises stress was calculated in the FEA to evaluate the biomechanical responses of the implants under increasing vertical and lateral loading, including the stress values of the implant, abutment, screw, crown, and cortical bone. RESULTS: The restorations on the left and right sides supported by double implants have been used for 6 and 12 years, respectively, and so far have shown excellent osseointegration radiographically.The von Mises stress calculated in the FEA showed that when the MDL was >14 mm, both the bone and prosthetic components bore more stress in the single implant-supported strategy. The strength was 188.62-201.37 MPa and 201.85-215.9 MPa when the MDL was 14 mm and 15 mm, respectively, which significantly exceeded the allowable yield stress (180 MPa). CONCLUSIONS: Compared with the single implant-supported crown, the double implant-supported crown reduced peri-implant bone stress and produced a more appropriate stress transfer model at the implant-bone interface when the MDL of the single missing molar was ≥14 mm.

Synthesis of a Triangle-Fused Six-Pointed Star and Its Electrocatalytic CO2 Reduction Activity.

As electrocatalysts, molecular catalysts with large aromatic systems (such as terpyridine, porphyrin, or phthalocyanine) have been widely applied in the CO2 reduction reaction (CO2RR). However, these monomeric catalysts tend to aggregate due to strong π-π interactions, resulting in limited accessibility of the active site. In light of these challenges, we present a novel strategy of active site isolation for enhancing the CO2RR. Six Ru(Tpy)2 were integrated into the skeleton of a metallo-organic supramolecule by stepwise self-assembly in order to form a rhombus-fused six-pointed star R1 with active site isolation. The turnover frequency (TOF) of R1 was as high as 10.73 s-1 at -0.6 V versus reversible hydrogen electrode (vs RHE), which is the best reported value so far at the same potential to our knowledge. Furthermore, by increasing the connector density on R1's skeleton, a more stable triangle-fused six-pointed star T1 was successfully synthesized. T1 exhibits exceptional stability up to 126 h at -0.4 V vs RHE and excellent TOF values of CO. The strategy of active site isolation and connector density increment significantly enhanced the catalytic activity by increasing the exposure of the active site. This work provides a starting point for the design of molecular catalysts and facilitates the development of a new generation of catalysts with a high catalytic performance.

Ferroelectric Domain Wall Delayer and Low-Dropout Regulator.

A switching-type power converter providing an accurate and stable switching output voltage against line/load variations and power supply ripple is mostly complicated in system-on-chip power management integrated circuits (PMICs) within a limited occupation area. Here we fabricated domain wall (DW) nanodevices using an X-cut LiNbO3 thin film on silicon. The domain switching event occurs after a delay time predicted by Merz's law under the applied voltage. But the output current is irrespective of the applied voltage and can be adjusted by conducting wall width as well as input resistance in the circuit. The regulating currents appear repetitively across the volatile interfacial domains between the nanodevice and electrode under intermittently applied voltages. A wall-current-limited domain switching model is developed to explain the phenomenon. The multifunctional DW nanodevices with smaller occupation areas can serve as compact low-dropout regulators in PMICs, time-domain delayers in energy-efficient neural network systems, and on-chip electrostatic discharge protection besides nonvolatile memories and selectors.

Regulatory mechanisms of autophagy on DHA and carotenoid accumulation in Crypthecodinium sp. SUN.

BACKGROUND: Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN. RESULTS: The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content. CONCLUSIONS: Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.

Radiomics for predicting MGMT status in cerebral glioblastoma: comparison of different MRI sequences.

Using radiomics to predict O6-methylguanine-DNA methyltransferase promoter methylation status in patients with newly diagnosed glioblastoma and compare the performances of different MRI sequences. Preoperative MRI scans from 215 patients were included in this retrospective study. After image preprocessing and feature extraction, two kinds of machine-learning models were established and compared for their performances. One kind was established using all MRI sequences (T1-weighted image, T2-weighted image, contrast enhancement, fluid-attenuated inversion recovery, DWI_b_high, DWI_b_low and apparent diffusion coefficient), and the other kind was based on single MRI sequence as listed above. For the machine-learning model based on all sequences, a total of seven radiomic features were selected with the Maximum Relevance and Minimum Redundancy algorithm. The predictive accuracy was 0.993 and 0.750 in the training and validation sets, respectively, and the area under curves were 1.000 and 0.754 in the two sets, respectively. For the machine-learning model based on single sequence, the numbers of selected features were 8, 10, 10, 13, 9, 7 and 6 for T1-weighted image, T2-weighted image, contrast enhancement, fluid-attenuated inversion recovery, DWI_b_high, DWI_b_low and apparent diffusion coefficient, respectively, with predictive accuracies of 0.797-1.000 and 0.583-0.694 in the training and validation sets, respectively, and the area under curves of 0.874-1.000 and 0.538-0.697 in the two sets, respectively. Specifically, T1-weighted image-based model performed best, while contrast enhancement-based model performed worst in the independent validation set. The machine-learning models based on seven different single MRI sequences performed differently in predicting O6-methylguanine-DNA methyltransferase status in glioblastoma, while the machine-learning model based on the combination of all sequences performed best.

The biological functions and pathological mechanisms of CASK in various diseases.

Background: As a scaffold protein, calcium/calmodulin-dependent serine protein kinase (CASK) has been extensively studied in a variety of tissues throughout the body. The Cask gene is ubiquitous in several tissues, such as the neurons, islets, heart, kidneys and sperm, and is mostly localised in the cytoplasm adjacent to the basement membrane. CASK binds to a variety of proteins through its domains to exerting its biological activity. Scope of review: Here, we discuss the role of CASK in multiple tissues throughout the body. The role of different CASK domains in regulating neuronal development, neurotransmitter release and synaptic vesicle secretion was emphasised; the regulatory mechanism of CASK on the function of pancreatic islet ß cells was analysed; the role of CASK in cardiac physiology, kidney and sperm development was discussed; and the role of CASK in different tumours was compared. Finally, we clarify the importance of the Cask gene in the body, and how deletion or mutation of the Cask gene can have adverse consequences. Major conclusions: CASK is a conserved gene with similar roles in various tissues. The function of the Cask gene in the nervous system is mainly involved in the development of the nervous system and the release of neurotransmitters. In the endocrine system, an involvement of CASK has been reported in the process of insulin vesicle transport. CASK is also involved in cardiomyocyte ion channel regulation, kidney and sperm development, and tumour proliferation. CASK is an indispensable gene for the whole body, and CASK mutations can cause foetal malformations or death at birth. In this review, we summarise the biological functions and pathological mechanisms of CASK in various systems, thereby providing a basis for further in-depth studies of CASK functions.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation.

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.

Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

Assessment of spilled oil dispersion affected by dispersant: Characteristic, stability, and related mechanism.

Oil dispersion, a crucial process in oil transport, involves the detachment of oil droplets from slicks and their introduction into the water column, influencing subsequent oil migration and transformation. This study examines oil dispersion, considering characteristics, stability, and mechanisms, while evaluating the impact of dispersants and salinity. Results show the significant role of surfactant type in dispersants on oil dispersion characteristics, with anionic surfactants exhibiting higher sensitivity to salinity changes compared to nonionic surfactants. The dispersion efficiency varies with salinity, with anionic surfactants performing better in low salinity (<20‰) and nonionic surfactants showing superior performance at 30-35‰ salinities. Rheological analysis illustrates the breakup and coalescence of oil droplets within the shear rates of breaking waves. An increase in interfacial film rigidity impedes the coalescence of oil droplets, contributing to the dynamic stability of the oil-water hybrid system. The use of GM-2, a nonionic dispersant, results in the formation of a solid-like interface, characterized by increased elastic modulus, notably at 20‰ salinity. However, stable droplet size distribution (DSD) at 35‰ salinity for 60 h suggests droplets can remain dispersed in seawater. The enhancement of stability of oil dispersion is interpreted as the result of two mechanisms: stabilizing DSD and developing the strength of viscoelastic interfacial film. These findings offer insights into oil dispersion dynamics, highlighting the importance of surfactant selection and salinity in governing dispersion behavior, and elucidating mechanisms underlying dispersion stability.

Correction: Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].

Female university students' fertility intentions and their psychosocial factors.

BACKGROUND: Raising the birth rate can effectively increase the resulting labour supply and minimise the adverse impact of an ageing population on high-quality economic development since the demographic dividend is rapidly declining. The Chinese government has a "three-child" policy in place, yet the fertility rate is still falling. This study intends to investigate the present fertility intentions of female university students and assess the extent to which feminism has affected their intentions. It will next investigate the degree to which and the mechanisms by which the psychosocial factors have an impact on those intentions. METHODS: A cross-sectional survey of female university students was conducted in Nanjing, China, from February to March 2023. To assure the representativeness of the sample, a technique of stratified proportional sampling, PPS sampling, and convenience sampling was utilized. A total of 1124 valid samples were acquired from female university students in 15 comprehensive universities. The data were mined and analysed by SPSS (version 24.0) and AMOS (version 24.0) software. RESULTS: Overall female university students' fertility intentions are low at this stage, with more than half (53.55%) of them having no clear desire to have children. The level of feminist identity significantly negatively affected the Intensity of desire to have children (-0.32) and child-number desires (-0.7). Psychosocial factors had a greater degree of influence on fertility intentions. The direct effect of the level of feminist identity and the perception of fertility hindrances on childbearing desires was -0.63 and -0.50 respectively, and the direct effect of the perception of fertility supports on childbearing intentions was 0.79. CONCLUSION: The level of feminist identity is significantly and negatively related to childbearing desires. Psychosocial factors have a greater degree of influence on fertility intentions, with the level of feminist identity, the perception of fertility hindrances and the perception of fertility supports all significantly impacting fertility intentions. The findings of this study emphasise the importance of the government providing a full range of social security and employers providing better employee benefits to promote a fertility-friendly society.

Artificial intelligence-powered pharmacovigilance: A review of machine and deep learning in clinical text-based adverse drug event detection for benchmark datasets.

OBJECTIVE: The primary objective of this review is to investigate the effectiveness of machine learning and deep learning methodologies in the context of extracting adverse drug events (ADEs) from clinical benchmark datasets. We conduct an in-depth analysis, aiming to compare the merits and drawbacks of both machine learning and deep learning techniques, particularly within the framework of named-entity recognition (NER) and relation classification (RC) tasks related to ADE extraction. Additionally, our focus extends to the examination of specific features and their impact on the overall performance of these methodologies. In a broader perspective, our research extends to ADE extraction from various sources, including biomedical literature, social media data, and drug labels, removing the limitation to exclusively machine learning or deep learning methods. METHODS: We conducted an extensive literature review on PubMed using the query "(((machine learning [Medical Subject Headings (MeSH) Terms]) OR (deep learning [MeSH Terms])) AND (adverse drug event [MeSH Terms])) AND (extraction)", and supplemented this with a snowballing approach to review 275 references sourced from retrieved articles. RESULTS: In our analysis, we included twelve articles for review. For the NER task, deep learning models outperformed machine learning models. In the RC task, gradient Boosting, multilayer perceptron and random forest models excelled. The Bidirectional Encoder Representations from Transformers (BERT) model consistently achieved the best performance in the end-to-end task. Future efforts in the end-to-end task should prioritize improving NER accuracy, especially for 'ADE' and 'Reason'. CONCLUSION: These findings hold significant implications for advancing the field of ADE extraction and pharmacovigilance, ultimately contributing to improved drug safety monitoring and healthcare outcomes.

DNA Bloom Filter enables anti-contamination and file version control for DNA-based data storage.

DNA storage is one of the most promising ways for future information storage due to its high data storage density, durable storage time and low maintenance cost. However, errors are inevitable during synthesizing, storing and sequencing. Currently, many error correction algorithms have been developed to ensure accurate information retrieval, but they will decrease storage density or increase computing complexity. Here, we apply the Bloom Filter, a space-efficient probabilistic data structure, to DNA storage to achieve the anti-error, or anti-contamination function. This method only needs the original correct DNA sequences (referred to as target sequences) to produce a corresponding data structure, which will filter out almost all the incorrect sequences (referred to as non-target sequences) during sequencing data analysis. Experimental results demonstrate the universal and efficient filtering capabilities of our method. Furthermore, we employ the Counting Bloom Filter to achieve the file version control function, which significantly reduces synthesis costs when modifying DNA-form files. To achieve cost-efficient file version control function, a modified system based on yin-yang codec is developed.

Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

Characterization of a novel anti-PVRIG antibody with Fc-competent function that exerts strong antitumor effects via NK activation in preclinical models.

Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.