Genome optimization via virtual simulation to accelerate maize hybrid breeding.

The employment of doubled-haploid (DH) technology in maize has vastly accelerated the efficiency of developing inbred lines. The selection of superior lines has to rely on genotypes with genomic selection (GS) model, rather than phenotypes due to the high expense of field phenotyping. In this work, we implemented 'genome optimization via virtual simulation (GOVS)' using the genotype and phenotype data of 1404 maize lines and their F1 progeny. GOVS simulates a virtual genome encompassing the most abundant 'optimal genotypes' or 'advantageous alleles' in a genetic pool. Such a virtually optimized genome, although can never be developed in reality, may help plot the optimal route to direct breeding decisions. GOVS assists in the selection of superior lines based on the genomic fragments that a line contributes to the simulated genome. The assumption is that the more fragments of optimal genotypes a line contributes to the assembly, the higher the likelihood of the line favored in the F1 phenotype, e.g. grain yield. Compared to traditional GS method, GOVS-assisted selection may avoid using an arbitrary threshold for the predicted F1 yield to assist selection. Additionally, the selected lines contributed complementary sets of advantageous alleles to the virtual genome. This feature facilitates plotting the optimal route for DH production, whereby the fewest lines and F1 combinations are needed to pyramid a maximum number of advantageous alleles in the new DH lines. In summary, incorporation of DH production, GS and genome optimization will ultimately improve genomically designed breeding in maize. Short abstract: Doubled-haploid (DH) technology has been widely applied in maize breeding industry, as it greatly shortens the period of developing homozygous inbred lines via bypassing several rounds of self-crossing. The current challenge is how to efficiently screen the large volume of inbred lines based on genotypes. We present the toolbox of genome optimization via virtual simulation (GOVS), which complements the traditional genomic selection model. GOVS simulates a virtual genome encompassing the most abundant 'optimal genotypes' in a breeding population, and then assists in selection of superior lines based on the genomic fragments that a line contributes to the simulated genome. Availability of GOVS (https://govs-pack.github.io/) to the public may ultimately facilitate genomically designed breeding in maize.

Hybrid photonic deep convolutional residual spiking neural networks for text classification.

Spiking neural networks (SNNs) offer powerful computation capability due to its event-driven nature and temporal processing. However, it is still limited to shallow structure and simple tasks due to the training difficulty. In this work, we propose a deep convolutional residual spiking neural network (DCRSNN) for text classification tasks. In the DCRSNN, the feature extraction is achieved via a convolution SNN with residual connection, using the surrogate gradient direct training technique. Classification is performed by a fully-connected network. We also suggest a hybrid photonic DCRSNN, in which photonic SNNs are used for classification with a converted training method. The accuracy of hard and soft reset methods, as well as three different surrogate functions, were evaluated and compared across four different datasets. Results indicated a maximum accuracy of 76.36% for MR, 91.03% for AG News, 88.06% for IMDB and 93.99% for Yelp review polarity. Soft reset methods used in the deep convolutional SNN yielded slightly better accuracy than their hard reset counterparts. We also considered the effects of different pooling methods and observation time windows and found that the convergence accuracy achieved by convolutional SNNs was comparable to that of convolutional neural networks under the same conditions. Moreover, the hybrid photonic DCRSNN also shows comparable testing accuracy. This work provides new insights into extending the SNN applications in the field of text classification and natural language processing, which is interesting for the resources-restrained scenarios.

Compression-Driven Internanocluster Reaction for Synthesis of Unconventional Gold Nanoclusters.

Can the active kernels in ultrasmall metal nanoparticles (nanoclusters, NCs) react with one another, or can the internanocluster reaction occur when they are in close enough proximity? To resolve this fundamental issue, we investigated the solid-state internanocluster reaction of the most studied gold NC Au25 (SR)18 (SR: thiolate). A novel NC was produced by increasing the pressure to 5 GPa, whose composition was determined to be Au32 (SC2 H4 Ph)24 by mass spectrometry and thermogravimetric analysis. As revealed by single-crystal X-ray crystallography, the structure, a bicuboid Au14 kernel and three pairs of interlocked trimetric staples, has not been reported and endows the NC with obvious photoluminescence. DFT calculations indicate that the staples contribute substantially to the absorption properties. Further experiments reveal the pressure (internanocluster distance) can tune the internanocluster reaction, and the resulting product is not necessarily the thermodynamic product.

Novel Hydrogen Clathrate Hydrate.

We report a new hydrogen clathrate hydrate synthesized at 1.2 GPa and 298 K documented by single-crystal x-ray diffraction, Raman spectroscopy, and first-principles calculations. The oxygen sublattice of the new clathrate hydrate matches that of ice II, while hydrogen molecules are in the ring cavities, which results in the trigonal R3c or R3[over ¯]c space group (proton ordered or disordered, respectively) and the composition of (H_{2}O)_{6}H_{2}. Raman spectroscopy and theoretical calculations reveal a hydrogen disordered nature of the new phase C_{1}^{'}, distinct from the well-known ordered C_{1} clathrate, to which this new structure transforms upon compression and/or cooling. This new clathrate phase can be viewed as a realization of a disordered ice II, unobserved before, in contrast to all other ordered ice structures.

Hydrogen Pentagraphenelike Structure Stabilized by Hafnium: A High-Temperature Conventional Superconductor.

The recent discovery of H_{3}S and LaH_{10} superconductors with record high superconducting transition temperatures T_{c} at high pressure has fueled the search for room-temperature superconductivity in the compressed superhydrides. Here we introduce a new class of high T_{c} hydrides with a novel structure and unusual properties. We predict the existence of an unprecedented hexagonal HfH_{10}, with remarkably high value of T_{c} (around 213-234 K) at 250 GPa. As concerns the novel structure, the H ions in HfH_{10} are arranged in clusters to form a planar "pentagraphenelike" sublattice. The layered arrangement of these planar units is entirely different from the covalent sixfold cubic structure in H_{3}S and clathratelike structure in LaH_{10}. The Hf atom acts as a precompressor and electron donor to the hydrogen sublattice. This pentagraphenelike H_{10} structure is also found in ZrH_{10}, ScH_{10}, and LuH_{10} at high pressure, each material showing a high T_{c} ranging from 134 to 220 K. Our study of dense superhydrides with pentagraphenelike layered structures opens the door to the exploration of a new class of high T_{c} superconductors.

Polymorphism of polymeric nitrogen at high pressures.

Polymeric nitrogen at 120 GPa-180 GPa is known in two monatomic crystalline cubic gauche (cg-N) and layered polymeric (LP-N) phases and one amorphous modification (η-N), and all these high-pressure phases attract considerable attention for their potential application as a high energy density material. Here, we investigated the stability of these modifications at high pressures in the laser heated diamond anvil cell upon decompression from 161 GPa. Pure LP-N was synthesized above 152 GPa upon laser heating of η-N to 2500 K, while cg-N forms below 150 GPa. Upon laser heating at 129 GPa and 123 GPa, the LP-N clearly diminished, indicating that the synthesis of cg-N becomes more favorable in a mixed phase region below 129 GPa. Upon unloading, cg-N and LP-N were metastable to at least 71 GPa at up to 2500 K and at room temperature, respectively. These observations clarified a complicated polymorphism of monatomic nitrogen at high pressures and large hysteretic phenomena related to a transition to nonmolecular nitrogen.

Helium-hydrogen immiscibility at high pressures.

Hydrogen and helium are the most abundant elements in the universe, and they constitute the interiors of gas giant planets. Thus, their equations of states, phase, chemical state, and chemical reactivity at extreme conditions are of great interest. Applying Raman spectroscopy, visual observation, and synchrotron X-ray diffraction in diamond anvil cells, we performed experiments on H2-He 1:1 and D2-He 1:10 compressed gas mixtures up to 100 GPa at 300 K. By comparing with the available data on pure bulk materials, we find no sign of miscibility, chemical reactivity, and new compound formation. This result establishes a new baseline for future investigations of miscibility in the He-H2 system at extreme P-T conditions.

Kinetic boundaries and phase transformations of ice i at high pressure.

Raman spectroscopy in diamond anvil cells has been employed to study phase boundaries and transformation kinetics of H2O ice at high pressures up to 16 GPa and temperatures down to 15 K. Ice i formed at nearly isobaric cooling of liquid water transforms on compression to high-density amorphous (HDA) ice at 1.1-3 GPa at 15-100 K and then crystallizes in ice vii with the frozen-in disorder (ice vii') which remains stable up to 14.1 GPa at 80 K and 15.9 GPa at 100 K. Unexpectedly, on decompression of ice vii', it transforms to ice viii in its domain of metastability, and then it relaxes into low-density amorphous (LDA) ice on a subsequent pressure release and warming up. On compression of ice i at 150-170 K, ice ix is crystallized and no HDA ice is found; further compression of ice ix results in the sequential phase transitions to stable ices vi and viii. Cooling ice i to 210 K at 0.3 GPa transforms it to a stable ice ii. Our extensive investigations provide previously missing information on the phase diagram of water, especially on the kinetic paths that result in formation of phases which otherwise are not accessible; these results are keys for understanding the phase relations including the formation of metastable phases. Our observations inform on the ice modifications that can occur naturally in planetary environments and are not accessible for direct observations.

Synthesis and Raman spectroscopy of a layered SiS2 phase at high pressures.

Dichalcogenides are known to exhibit layered solid phases, at ambient and high pressures, where 2D layers of chemically bonded formula units are held together by van der Waals forces. These materials are of great interest for solid-state sciences and technology, along with other 2D systems such as graphene and phosphorene. SiS2 is an archetypal model system of the most fundamental interest within this ensemble. Recently, high pressure (GPa) phases with Si in octahedral coordination by S have been theoretically predicted and also experimentally found to occur in this compound. At variance with stishovite in SiO2, which is a 3D network of SiO6 octahedra, the phases with octahedral coordination in SiS2 are 2D layered. Very importantly, this type of semiconducting material was theoretically predicted to exhibit continuous bandgap closing with pressure to a poor metallic state at tens of GPa. We synthesized layered SiS2 with octahedral coordination in a diamond anvil cell at 7.5-9 GPa, by laser heating together elemental S and Si at 1300-1700 K. Indeed, Raman spectroscopy up to 64.4 GPa is compatible with continuous bandgap closing in this material with the onset of either weak metallicity or of a narrow bandgap semiconductor state with a large density of defect-induced, intra-gap energy levels, at about 57 GPa. Importantly, our investigation adds up to the fundamental knowledge of layered dichalcogenides.

Subchronic toxicity study in rats evaluating genetically modified DAS-81419-2 soybean.

A 90-day feeding study in rats was conducted to evaluate the subchronic oral toxicity of genetically modified (GM) DAS-81419-2 soybean. Wistar rats were fed with diets containing toasted soybean meal produced from DAS-81419-2 soybean grain that expresses the Cry1F, Cry1Ac, and Pat proteins or containing conventional soybean at doses of 30.0%, 15.0%, 7.5%, or 0% (control group) for 90 consecutive days. The general behavior, body weight and food consumption were observed. At the middle and end of the experiment, blood, serum, and urine samples were collected for biochemical assays. At the conclusion of the study, the internal organs were weighed and histopathological examination was completed. The rats exhibited free movement and shiny coats without any abnormal symptoms or abnormal secretions in their noses, eyes, or mouths. There were no adverse effects on body weight in GM soybean groups and conventional soybean groups. No biological differences in hematological, biochemical, or urine indices were observed. No significant differences in relative organ weights were detected between the experimental groups and the control group. No histopathological changes were observed. Under the conditions of this study, DAS-81419-2 soybean did not cause any treatment-related effects in Wistar rats following 90 days of dietary administration.

Experimental verification of the high pressure crystal structures in NH3BH3.

A detailed high-pressure study on NH3BH3 has been carried out using in situ synchrotron X-ray diffraction (XRD) and Raman scattering with a diamond anvil cell up to 20 and 33 GPa, respectively. The Rietveld refinement based on the XRD pattern and analysis of Raman data indicate two first-order phase transitions from the ambient pressure I4 mm structure (α-NH3BH3) to a high pressure Cmc21 phase (ß-NH3BH3) at 2.14 GPa, and further into a monoclinic P21 (Z = 2) phase (γ-NH3BH3) at 9.67 GPa. Fitting the measured volumetric compression data to the third order Birch-Murnaghan equation of state reveals a bulk modulus of B0 = 9.9 ± 0.5 and 17.0 ± 3.0 GPa (with fixed B0 (') = 4) for the ß-NH3BH3 below and above 5 GPa, respectively. Still, with the splitting of the NBH rock mode in Raman experiment, it is concluded that a second-order isostructural phase transition occurs at 5 GPa. By analyzing the dihydrogen bonding framework, the origin of the isostructural phase transition is attributed to the number of dihydrogen bondings per molecule in the Cmc21 phase increasing from 12 to 14 at 5 GPa.

[Effects of nanosized cadmium sulfide on male reproductive system in mice].

OBJECTIVE: To investigate the effects of nanosized cadmium sulfide (nano-CdS) on the male reproductive system in mice. METHODS: Thirty-six specific pathogen?free male ICR mice were equally and randomly divided into three groups: two experimental groups and a control group. The two experimental groups were exposed to 100 mg/kg and 50 mg/kg nano-CdS once daily by gavage, respectively, while the control group was exposed to the same volume of physiological saline once daily by gavage. After 45 days, levels of cadmium accumulation and serum testosterone in the testis were determined, the epididymal sperm count, the rate of sperm abnormality, and histopathological changes in testis tissue were observed under a microscope, and the level of CYP11A1 mRNA was determined by qRT-PCR. RESULTS: Compared with the control group, the two experimental groups had a significantly increased level of cadmium accumulation in the testis (P < 0.05), and the 100 mg/kg nano-CdS group had a significantly decreased epididymal sperm count (P < 0.05) and a significantly increased rate of sperm abnormality (P < 0.05), but the 50 mg/kg nano-CdS group did not. The 100 mg/kg nano-CdS group showed different histopathological changes in testis tissue, but the 50 mg/kg nano-CdS group did not. The two experimental groups had significantly reduced levels of testosterone and CYP11A1 mRNA compared with the control group. CONCLUSION: Nano-CdS given through the digestive tract may have an effect on the male reproductive system in mice by affecting the key enzyme genes in the androgen synthesis pathway to reduce the levels of reproductive hormones.

Prediction of Room-Temperature Superconductivity in Quasi-Atomic H2-Type Hydrides at High Pressure.

Achieving superconductivity at room temperature (RT) is a holy grail in physics. Recent discoveries on high-Tc superconductivity in binary hydrides H3S and LaH10 at high pressure have directed the search for RT superconductors to compress hydrides with conventional electron-phonon mechanisms. Here, an exceptional family of superhydrides is predicated under high pressures, MH12 (M = Mg, Sc, Zr, Hf, Lu), all exhibiting RT superconductivity with calculated Tcs ranging from 313 to 398 K. In contrast to H3S and LaH10, the hydrogen sublattice in MH12 is arranged as quasi-atomic H2 units. This unique configuration is closely associated with high Tc, attributed to the high electronic density of states derived from H2 antibonding states at the Fermi level and the strong electron-phonon coupling related to the bending vibration of H2 and H-M-H. Notably, MgH12 and ScH12 remain dynamically stable even at pressure below 100 GPa. The findings offer crucial insights into achieving RT superconductivity and pave the way for innovative directions in experimental research.

One-Dimensional Non-coplanar Nitrogen Chains in Manganese Tetranitride under High Pressure.

Transition metal nitrides have great potential applications as incompressible and high energy density materials. Various polymeric nitrogen structures significantly affect their properties, contributing to their complex bonding modes and coordination conditions. Herein, we first report a new manganese polynitride MnN4 with bifacial trans-cis [N4]n chains by treating with high-pressure and high-temperature conditions in a diamond anvil cell. Our experiments reveal that MnN4 has a P-1 symmetry and could stabilize in the pressure range of 56-127 GPa. Detailed pressure-volume data and calculations of this phase indicate that MnN4 is a potential hard (255 GPa) and high energy density (2.97 kJ/g) material. The asymmetric interactions impel N1 and N4 atoms to hybridize to sp2-3, which causes distortions of [N4]n chains. This work discovers a new polynitride material, fills the gap for the study of manganese polynitride under high pressure, and offers some new insights into the formation of polymeric nitrogen structures.

Stabilization of High-Pressure Phase of Face-Centered Cubic Lutetium Trihydride at Ambient Conditions.

Superconductivity at room temperature and near-ambient pressures is a highly sought-after phenomenon in physics and materials science. A recent study reported the presence of this phenomenon in N-doped lutetium hydride [Nature 615, 244 (2023)], however, subsequent experimental and theoretical investigations have yielded inconsistent results. This study undertakes a systematic examination of synthesis methods involving high temperatures and pressures, leading to insights into the impact of the reaction path on the products and the construction of a phase diagram for lutetium hydrides. Notably, the high-pressure phase of face-centered cubic LuH3 (fcc-LuH3) is maintained to ambient conditions through a high-temperature and high-pressure method. Based on temperature and anharmonic effects corrections, the lattice dynamic calculations demonstrate the stability of fcc-LuH3 at ambient conditions. However, no superconductivity is observed above 2 K in resistance and magnetization measurements in fcc-LuH3 at ambient pressure. This work establishes a comprehensive synthesis approach for lutetium hydrides, thereby enhancing the understanding of the high-temperature and high-pressure method employed in hydrides with superconductivity deeply.

Frontier in the diamond anvil cell techniques for ultrahigh pressure generation.

The diamond anvil cell (DAC) has become a principal tool for high-pressure research in muti-fields such as physics, earth, and planetary sciences, because of its ability to the realization of megabar pressures and thousands of degrees. Nevertheless, the strain on the culet of single crystal diamond at high loads leads to the conventional DAC having a 400 GPa limit. To date, based on the conventional DAC, several new designs were innovatively proposed, such as the double stage DAC (ds-DAC) and toroidal DAC. They are both capable to reach pressures above 600 GPa, and even static pressures of more than 1.0 TPa are achieved using ds-DAC. All these progresses promote the exploration of unique properties and new matters in a remarkable extended pressure range. Here, the typical characteristics and experimental methods of these interesting and important ultrahigh-pressure technologies are reviewed, the strengths and limitations are summarized, and an outlook on the development of ultrahigh-pressure technology is also provided. These exciting results will further stimulate breakthrough discoveries for ultrahigh-pressure studies.

[Predictive value of early lactate/albumin ratio in the prognosis of sepsis].

OBJECTIVE: To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis. METHODS: A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed. RESULTS: A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95%CI) of lactate, albumin, and L/A were 0.794 (95%CI was 0.741-0.840), 0.589 (95%CI was 0.528-0.647), 0.807 (95%CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. CONCLUSIONS: The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

Restoration of saturated outputs from microchannel plate photomultiplier tubes in sub-microsecond single-pulse-current mode.

Microchannel plate (MCP) photomultiplier tubes (PMTs) are frequently used in experimental diagnostics, where they are operated in single-pulse current measurement mode. However, considering the significant amplitude fluctuations in the measured signal, the resulting output signal from the MCP-PMT is inevitably distorted by gain saturation. Therefore, understanding the correlation between the MCP-PMT output signal and gain saturation is critical in assessing the extent of output signal distortion and determining the MCP-PMT saturation level. This knowledge allows for a more precise assessment of the input signal's features. In this paper, we present an experimental method for restoring the initial waveform from the saturated MCP-PMT signal. To correct the amplitude-drop caused by gain saturation, our technique involves calibrating the MCP-PMT's relative gain as a function of the accumulated output charge using a square-wave light source. We then applied this approach to restore a ∼500 ns saturated pulse from a double-layer 10 mm diameter MCP-PMT. The restored signal showed a deviation of less than 6% from the reference waveform, which validates the effectiveness of the technique.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.