Transplanted MSCs promote alveolar bone repair via hypoxia-induced extracellular vesicle secretion.

OBJECT: Mesenchymal stem cell (MSC) therapy is a potential strategy for promoting alveolar bone regeneration. This study evaluated the effects and mechanisms of transplanted MSCs on alveolar bone repair. METHODS: Mouse alveolar bone defect model was treated using mouse bone marrow mesenchymal stem cell (BMSC) transplantation. The bone repair was evaluated by micro-CT and Masson staining. The conditioned medium of hypoxia-treated BMSCs was co-cultured with normal BMSCs in vitro to detect the regulatory effect of transplanted MSCs on the chemotactic and migratory functions of host cells. The mechanisms were investigated using Becn siRNA transfection and western blotting. RESULTS: BMSC transplantation promoted bone defect regeneration. The hypoxic microenvironment induces BMSCs to release multiple extracellular vesicle (EV)-mediated regulatory proteins that promote the migration of host stem cells. Protein array analysis, western blotting, GFP-LC3 detection, and Becn siRNA transfection confirmed that autophagy activation in BMSCs plays a key role during this process. CONCLUSION: The local hypoxic microenvironment induces transplanted MSCs to secrete a large number of EV-mediated regulatory proteins, thereby upregulating the migration function of the host stem cells and promoting alveolar bone defect regeneration. This process depends on the autophagy-related mechanism of the transplanted MSCs.

Self-Supervised Image Denoising of Third Harmonic Generation Microscopic Images of Human Glioma Tissue by Transformer-based Blind Spot (TBS) Network.

Third harmonic generation (THG) microscopy shows great potential for instant pathology of brain tumor tissue during surgery. However, due to the maximal permitted exposure of laser intensity and inherent noise of the imaging system, the noise level of THG images is relatively high, which affects subsequent feature extraction analysis. Denoising THG images is challenging for modern deep-learning based methods because of the rich morphologies contained and the difficulty in obtaining the noise-free counterparts. To address this, in this work, we propose an unsupervised deep-learning network for denoising of THG images which combines a self-supervised blind spot method and a U-shape Transformer using a dynamic sparse attention mechanism. The experimental results on THG images of human glioma tissue show that our approach exhibits superior denoising performance qualitatively and quantitatively compared with previous methods. Our model achieves an improvement of 2.47-9.50 dB in SNR and 0.37-7.40 dB in CNR, compared to six recent state-of-the-art unsupervised learning models including Neighbor2Neighbor, Blind2Unblind, Self2Self+, ZS-N2N, Noise2Info and SDAP. To achieve an objective evaluation of our model, we also validate our model on public datasets including natural and microscopic images, and our model shows a better denoising performance than several recent unsupervised models such as Neighbor2Neighbor, Blind2Unblind and ZS-N2N. In addition, our model is nearly instant in denoising a THG image, which has the potential for real-time applications of THG microscopy.

Effect of electroacupuncture stimulation of "Sibai"(ST2) and "Quanliao"(SI18) on excitatory neurons of sensorimotor cortex in mice. / 电针"四白"和"颧髎"æ¿€æ´»å°é¼ èº¯ä½“æ„Ÿè§‰è¿åŠ¨çš®å±‚çš„å ´å¥‹æ€§ç¥žç»å ƒ.

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.

Incorporation of cellulose nanocrystals to improve the physicochemical and bioactive properties of pectin-konjac glucomannan composite films containing clove essential oil.

This study aimed to investigate the effectiveness of cellulose nanocrystals (CNC) isolated from cotton in augmenting pectin (PEC)/konjac glucomannan (KGM) composite films containing clove essential oil (CEO) for food packaging application. The effects of CNC dosage on film properties were examined by analyzing the rheology of film-forming solutions and the mechanical, barrier, antimicrobial, and CEO-release properties of the films. Rheological and FTIR analysis revealed the enhanced interactions among the film components after CNC incorporation due to its high aspect ratio and abundant hydroxyl groups, which can also prevent CEO droplet aggregation, contributing to form a compact microstructure as confirmed by SEM and 3D surface topography observations. Consequently, the addition of CNC reinforced the polysaccharide matrix, increasing the tensile strength of the films and improving their barrier properties to water vapor. More importantly, antibacterial, controlled release and kinetic simulation experiments proved that the addition of CNC could further slow down the release rate of CEO, prolonging the antimicrobial properties of the films. PEC/KGM/CEO composite films with 15 wt% CNC was found to have relatively best comprehensive properties, which was also most effective in delaying deterioration of grape quality during the storage of 9 days at 25 °C.

Comprehensive profiling of enhancer RNA in stage II/III colorectal cancer defines two prognostic subtypes with implications for immunotherapy.

BACKGROUND: Recently, enhancer RNAs (eRNAs) have garnered attention as pivotal biomarkers for the onset and progression of cancer. However, the landscape of eRNAs and the implications of eRNA-based molecular subtypes in stage II/III colorectal cancer (CRC) remain largely unexplored. METHODS: Comprehensive profiling of eRNAs was conducted on a public stage II/III CRC cohort with total RNA-seq data. We used unsupervised clustering of prognostic eRNAs to establish an eRNA-based subtyping system. Further evaluations included molecular characteristics, immune infiltration, clinical outcomes, and drug responses. Finally, we validated the eRNA-based subtyping system in The Cancer Genome Atlas (TCGA) CRC cohort. RESULTS: We identified a total of 6453 expressed eRNAs, among which 237 were prognostic. A global upregulation of eRNAs was observed in microsatellite-stable (MSS) CRCs when compared to microsatellite instability-high (MSI-H) CRCs. Through consensus clustering, two novel molecular subtypes, termed Cluster 1(C1) and Cluster 2(C2), were further identified. C1, associated with the activation of epithelial-mesenchymal transition (EMT), hypoxia, and KRAS signaling pathways, showed poorer prognosis. C2, correlated with the canonical CRC subtype, exhibited superior survival outcomes. In addition, C1 showed enrichment with immune infiltration and more sensitivity to immune checkpoint inhibitors. CONCLUSION: Our study unravels the molecular heterogeneity of stage II/III CRC at the eRNA level and highlights the potential applications of the novel eRNA-based subtyping system in predicting prognosis and guiding immunotherapy.

Study on Porosity of Thermal-Sprayed Commercially Pure Aluminum Coating.

Porosity is closely related to the corrosion and wear properties of a coating processed by thermal-spraying technology, and the quantitative characterization of porosity is a crucial part of the research on coating structures. The current image analysis method often uses the mechanical polishing method recommended by ISO to measure a coating porosity. This method has been proved to be an effective method for the characterization of oxide coatings. However, due to the significant differences in the physical and chemical properties between aluminum and oxides, this method may not be suitable for aluminum coatings, and a more appropriate approach needs to be explored. In this paper, the effects of three polishing technologies (mechanical polishing, argon-ion-beam polishing, and electrolytic polishing) on the porosity measurement of pure aluminum coatings were compared and studied. The research results showed that the commonly used mechanical polishing method and more advanced argon-ion-beam polishing method could not completely reveal the pore structure because SiC particles would be embedded in the pure aluminum coatings during mechanical polishing, filling large pores. Although electrolytic polishing technology had advantages in revealing the macroporous structure, it would introduce a microporous structure and oxides, which would affect the measurement of the coating porosity. The composite polishing technology (electrolytic polishing + argon-ion-beam polishing) could perfectly reveal the pore structure in the pure-aluminum coating, and the porosity of arc-sprayed aluminum coating was 9.9%, which was close to the macroscopic true value measured using the weighing method of 10.2%.

Alterations in gp120 glycans or the gp41 fusion peptide-proximal region modulate the stability of the human immunodeficiency virus (HIV-1) envelope glycoprotein pretriggered conformation.

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer mediates entry into host cells by binding receptors, CD4 and CCR5/CXCR4, and fusing the viral and cell membranes. In infected cells, cleavage of the gp160 Env precursor yields the mature Env trimer, with gp120 exterior and gp41 transmembrane Env subunits. Env cleavage stabilizes the State-1 conformation, which is the major target for broadly neutralizing antibodies, and decreases the spontaneous sampling of more open Env conformations that expose epitopes for poorly neutralizing antibodies. During HIV-1 entry into cells, CD4 binding drives the metastable Env from a pretriggered (State-1) conformation into more "open," lower-energy states. Here, we report that changes in two dissimilar elements of the HIV-1 Env trimer, namely particular gp120 glycans and the gp41 fusion peptide-proximal region (FPPR), can independently modulate the stability of State 1. Individual deletion of several gp120 glycans destabilized State 1, whereas removal of a V1 glycan resulted in phenotypes indicative of a more stable pretriggered Env conformation. Likewise, some alterations of the gp41 FPPR decreased the level of spontaneous shedding of gp120 from the Env trimer and stabilized the pretriggered State-1 Env conformation. State-1-stabilizing changes were additive and could suppress the phenotypes associated with State-1-destabilizing alterations in Env. Our results support a model in which multiple protein and carbohydrate elements of the HIV-1 Env trimer additively contribute to the stability of the pretriggered (State-1) conformation. The Env modifications identified in this study will assist efforts to characterize the structure and immunogenicity of the metastable State-1 conformation. IMPORTANCE The elicitation of antibodies that neutralize multiple strains of HIV-1 is an elusive goal that has frustrated the development of an effective vaccine. The pretriggered shape of the HIV-1 envelope glycoprotein (Env) spike on the virus surface is the major target for such broadly neutralizing antibodies. The "closed" pretriggered Env shape resists the binding of most antibodies but is unstable and often assumes "open" shapes that elicit ineffective antibodies. We identified particular changes in both the protein and the sugar components of the Env trimer that stabilize the pretriggered shape. Combinations of these changes were even more effective at stabilizing the pretriggered Env than the individual changes. Stabilizing changes in Env could counteract the effect of Env changes that destabilize the pretriggered shape. Locking Env in its pretriggered shape will assist efforts to understand the Env spike on the virus and to incorporate this shape into vaccines.

SlbHLH152, a bHLH transcription factor positively regulates iron homeostasis in tomato.

The maintain of iron (Fe) homeostasis is essential for plant survival. In tomato, few transcription factors have been identified as regulators of Fe homeostasis, among which SlbHLH068 induced by iron deficiency, plays an important role. However, the upstream regulator(s) responsible for activating the expression of SlbHLH068 remain(s) unknown. In this study, the bHLH (basic helix-loop-helix) transcription factor SlbHLH152 was identified as an upstream regulator of SlbHLH068 using yeast one-hybrid screening. Deletion of SlbHLH152 led to a significant decline in Fe concentration, which was accompanied by reduced expression of Fe-deficiency-responsive genes. In contrast, SlbHLH152 overexpression plants displayed tolerance to iron deficiency, increased Fe accumulation, and elevated expression of Fe-deficiency-responsive genes. Further analysis indicated that SlbHLH152 directly activates the transcription of SlbHLH068. Taken together, our results suggest that SlbHLH152 may be involved in the regulation of iron homeostasis by directly activating the transcription of SlbHLH068 in tomato.

A review of regeneration mechanism and methods for reducing soot emissions from diesel particulate filter in diesel engine.

With the global emphasis on environmental protection and the proposal of the climate goal of "carbon neutrality," countries around the world are calling for reductions in carbon dioxide, nitrogen oxide, and particulate matter pollution. These pollutants have severe impacts on human lives and should be effectively controlled. Engine exhaust is the most serious pollution source, and diesel engine is an important contributor to particulate matter. Diesel particulate filter (DPF) technology has proven to be an effective technology for soot control at the present and in the future. Firstly, the exacerbating effect of particulate matter on human infectious disease viruses is discussed. Then, the latest developments in the influence of key factors on DPF performance are reviewed at different observation scales (wall, channel, and entire filter). In addition, current soot catalytic oxidant schemes are presented in the review, and the significance of catalyst activity and soot oxidation kinetic models are highlighted. Finally, the areas that need further research are determined, which has important guiding significance for future research. Current catalytic technologies are focused on stable materials with high mobility of oxidizing substances and low cost. The challenge of DPF optimization design is to accurately calculate the balance between soot and ash load, DPF regeneration control strategy, and exhaust heat management strategy.

Effects of cinnamon essential oil-loaded Pickering emulsion on the structure, properties and application of chayote tuber starch-based composite films.

The use of non-conventional starch sources to develop biodegradable and bioactive starch-based films have attracted increasing attention recently. In this study, a nonconventional chayote tuber starch (CTS) was functionalized by zein-pectin nanoparticle-stabilized cinnamon essential oil (CEO) Pickering emulsion (ZPCO) to develop a novel bioactive composite films for food packaging application. Results demonstrated that antibacterial ZPCO featuring long-term stability was successfully obtained. FTIR and SEM analyses suggested that ZPCO have favorable dispersibility and compatibility with CTS matrix. With ZPCO increasing, the transmittance, tensile strength, and moisture content of composite films decreased, whereas their elongation at break, antimicrobial and antioxidant activities increased. ZPCO added at an appropriate level (2 %) can improve water-resistance of the films and reduce water vapor permeability. More importantly, ZPCO can achieve a slower sustained-release of CEO from composite films into food simulants. Furthermore, the composite film containing 2 % ZPCO is safe and nontoxic as proved by cell cytotoxicity test, and it can significantly prolong the shelf life of ground beef by showing the lowest total volatile base nitrogen and best acceptable sensory characteristic. Overall, the incorporation of ZPCO into CTS films offers a great potential application as a bioactive material in the food packing.

A nucleolin-activated polyvalent aptamer nanoprobe for the detection of cancer cells.

Sensitive detection of cancer cells plays a critical role in early cancer diagnosis. Nucleolin, overexpressed on the surface of cancer cells, is regarded as a candidate biomarker for cancer diagnosis. Thus, cancer cells can be detected through the detection of membrane nucleolin. Herein, we designed a nucleolin-activated polyvalent aptamer nanoprobe (PAN) to detect cancer cells. In brief, a long single-stranded DNA with many repeated sequences was synthesized through rolling circle amplification (RCA). Then the RCA product acted as a scaffold chain to combine with multiple AS1411 sequences, which was doubly modified with fluorophore and quenching group, respectively. The fluorescence of PAN was initially quenched. Upon binding to target protein, the conformation of PAN changed, leading to the recovery of fluorescence. The fluorescence signal of cancer cells treated with PAN was much brighter compared with that of monovalent aptamer nanoprobes (MAN) at the same concentration. Furthermore, the binding affinity of PAN to B16 cells was proved to be 30 times higher than that of MAN by calculating the dissociation constants. The results indicated that PAN could specifically detect target cells, and this design concept has potential to become promising in cancer diagnosis.

Pectin mediates the mechanism of host blood glucose regulation through intestinal flora.

Pectin is a complex polysaccharide found in plant cell walls and interlayers. As a food component, pectin is benefit for regulating intestinal flora. Metabolites of intestinal flora, including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), are involved in blood glucose regulation. SCFAs promote insulin synthesis through the intestine-GPCRs-derived pathway and hepatic adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway to promote hepatic glycogen synthesis. On the one hand, BAs stimulate intestinal L cells and pancreatic α cells to secrete Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) through receptors G protein-coupled receptor (TGR5) and farnesoid X receptor (FXR). On the other hand, BAs promote hepatic glycogen synthesis through AMPK pathway. LPS inhibits the release of inflammatory cytokines through Toll-like receptors (TLRs)-myeloid differentiation factor 88 (MYD88) pathway and mitogen-activated protein kinase (MAPK) pathway, thereby alleviating insulin resistance (IR). In brief, both SCFAs and BAs promote GLP-1 secretion through different pathways, employing strategies of increasing glucose consumption and decreasing glucose production to maintain normal glucose levels. Notably, pectin can also directly inhibit the release of inflammatory cytokines through the -TLRs-MYD88 pathway. These data provide valuable information for further elucidating the relationship between pectin-intestinal flora-glucose metabolism.

Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia?

Ciprofol is a novel compound that was independently developed in China. According to the Chinese product instructions approved by the China National Medical Products Administration and the information of official website, indications for ciprofol include sedation and anesthesia during the surgical/procedure of nontracheal intubation, induction and maintenance of general anesthesia, and sedation during intensive care. Ciprofol is a short-acting intravenous sedative based on the structural modification of propofol. Ciprofol has high efficacy, good selectivity, and fewer adverse reactions, indicating good clinical application potential. A series of clinical studies have been conducted to evaluate the sedative effect of ciprofol in various procedures and settings, including gastroscopy and colonoscopy, fiber-optic bronchoscopy, general anesthesia in elective surgeries, and mechanical ventilation in intensive care units. This review summarizes the chemical structure, pharmacodynamics, and pharmacokinetic properties of ciprofol. We also assessed the efficacy and safety of ciprofol by synthesizing the relevant clinical trial data.

A more accurate indicator to evaluate oxidative stress in rat plasma with osteoporosis.

Background: oxidative stress is linked to various human diseases which developed into the idea of "disrupted redox signaling". Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mineral density and deterioration of bone microarchitecture among which estrogen deficiency is the main cause. Lack of estrogen leads to the imbalance between oxidation and anti-oxidation in patients, and oxidative stress is an important link in the pathogenesis of OP. The ratio of the reduced to the oxidized thiols can characterize the redox status. However, few methods have been reported for the simultaneous determination of reduced forms and their oxidized forms of thiols in plasma. Methods: we developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation and validated a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method to determine two reduced forms of thiols-homocysteine (Hcy), cysteine (Cys) levels and their respective oxidized compounds, homocystine (HHcy) and cystine (Cyss) in rat plasma simultaneously for the first time. Thirty-six female rats were randomly divided into three groups: normal control (NC), oxidative stress (ovariectomy, OVX) and ovariectomy with hydrogen-rich saline administration (OVX + HRS). Results: the validation parameters for the methodological results were within the acceptance criteria. There were both significant differences of Hcy/HHcy (Hcy reduced/oxidized) and Cys/Cyss (Cys reduced/oxidized) in rat plasma between three groups with both p < 0.05 and meanwhile, the p values of malondialdehyde, superoxide dismutase and glutathione peroxidase were all less than 0.01. The value of both Hcy/HHcy and Cys/Cyss were significantly decreased with the change of Micro-CT scan result of femoral neck in OVX group (both the trabecular thickness and trabecular number significantly decreased with a significant increase of trabecular separation) which demonstrate OP occurs. The change of Hcy/HHcy is more obvious and prominent than Cys/Cyss. Conclusions: the Hcy/HHcy and Cys/Cyss could be suitable biomarkers for oxidative stress and especially Hcy/HHcy is more sensitive. The developed method is simple and accurate. It can be easily applied in clinical research to further evaluate the oxidative stress indicator for disease risk factors.

Peptide profiles and allergy-reactivity of extensive hydrolysates of milk protein.

Milk protein concentrate (MPC) is one of the major allergens in food. This study aimed to analyze the peptide profiles and potential allergenicity of the extensive hydrolysates of MPC (EMPHs) using the peptidomics approach. Results demonstrated that when the hydrolysis time was 4 h, the degree of hydrolysis of the four EMPHs (AX, Alcalase-Protamex), (AD, Alcalase-Protease A 2SD), (AE, Alcalase-Flavourzyme) and (AH, Alcalase-ProteAXH) were 12.45 %, 18.48 %, 18.87 % and 16.77 %, respectively. The results of size exclusion chromatography showed no significant difference, when the hydrolysis time exceeded 3 h. A total of 16 allergic peptides were identified in the EMPHs by LC-MS/MS. The peptide profiles and the coverage of master protein of the four EMPHs were different. The results of the enzyme-linked immunoassay and KU812 cell model showed that the allergenicity of the EMPHs samples was significantly reduced. This study provided strong support for the application of EMPHs in hypoallergenic formula foods.

Rolling Circle Amplification-Based DNA Nano-Assembly for Targeted Drug Delivery and Gene Therapy.

Combining the killing ability of chemotherapy drugs on tumor cells with the inhibiting ability of genetic drugs on tumor cell growth, a dual drug delivery system loaded with therapy drugs and siRNA has gradually received more and more research and extensive attention. In this paper, we designed a DNA nano-assembly based on rolling circle amplification that can co-deliver doxorubicin (Dox) and siRNA simultaneously. In order to fully exploit the potential of the dual loading system in cancer treatment, we selected STAT3 gene as a target and used siRNA to target STAT3 of mRNA and reduce the STAT3 expression in mouse melanoma cell line (B16); meanwhile, Dox as a chemotherapy drug was combined with multivalent aptamers specifically targeting B16 to achieve efficient delivery of siRNA and Dox. The results showed that the synergistic delivery system could achieve high efficiency in targeting and inhibiting proliferation in mouse melanoma cells. In addition, the synergistic effect of the dual delivery system on apoptosis of cancer cells was significantly better than that of single drug delivery systems.

Effects of High-Pressure Homogenization Treatment on the Development of Antioxidant Zanthoxylum bungeanum Leaf Powder Films for Preservation of Fresh-Cut Apple.

This study determined that Zanthoxylum bungeanum leaves (ZBLs) are rich in functional components such as cellulose, protein, flavone, and polyphenols. Therefore, they were used as the main raw material, with sodium alginate as a thickener and glycerol as a plasticizer, to investigate the preparation of active films from ZBL powder through high-pressure homogenization (HPH). The physical, optical, mechanical, and antioxidant properties of the films were evaluated, and their application in preserving fresh-cut apples was examined. The results showed that the optimal concentration of ZBL powder was 1.5% under a 30 MPa HPH treatment. The resulting HPH-treated films exhibited a denser microstructure and improved water vapor barrier properties and mechanical strength. Compared to the films without HPH treatment, the tensile strength increased from 4.61 MPa to 12.13 MPa, the elongation at break increased from 21.25% to 42.86%, the water vapor permeability decreased from 9.9 × 10-9 g/m·s·Pa to 8.0 × 10-9 g/m·s·Pa, and the transparency increased from 25.36% to 38.5%. Compared to the control group, the fresh-cut apples packaged with the HPH-treated ZBL active films exhibited effective preservation of apple quality during a five-day period at 4 °C and 70% humidity, showing better preservation effects than the other groups. In conclusion, the use of HPH treatment in developing novel biopolymer active films from ZBL powders with enhanced properties holds potential for various applications.

Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer.

Here we studied expression and potential functions of Gαi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gαi3 expression was remarkably elevated in human cervical cancer tissues and different cervical cancer cells, and was associated with poor overall survival and poor disease-specific survival of patients. Gαi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gαi3 shRNA or CRISPR/Cas9-caused Gαi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gαi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gαi3 silencing or KO, but was augmented following Gαi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gαi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gαi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after Gαi3 silencing or KO. Gαi3 depletion and Akt-mTOR inactivation were detected in Gαi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gαi3 is a valuable oncotarget of cervical cancer.