Identification of a novel hypoglycemic small molecule, trans-2, 4-dimethoxystilbene by rectifying gut microbiota and activating hepatic AMPKα-PPARγ pathway through gut-liver axis.

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.

Tensor Robust Kernel PCA for Multidimensional Data.

Recently, the tensor nuclear norm (TNN)-based tensor robust principle component analysis (TRPCA) has achieved impressive performance in multidimensional data processing. The underlying assumption in TNN is the low-rankness of frontal slices of the tensor in the transformed domain (e.g., Fourier domain). However, the low-rankness assumption is usually violative for real-world multidimensional data (e.g., video and image) due to their intrinsically nonlinear structure. How to effectively and efficiently exploit the intrinsic structure of multidimensional data remains a challenge. In this article, we first suggest a kernelized TNN (KTNN) by leveraging the nonlinear kernel mapping in the transform domain, which faithfully captures the intrinsic structure (i.e., implicit low-rankness) of multidimensional data and is computed at a lower cost by introducing kernel trick. Armed with KTNN, we propose a tensor robust kernel PCA (TRKPCA) model for handling multidimensional data, which decomposes the observed tensor into an implicit low-rank component and a sparse component. To tackle the nonlinear and nonconvex model, we develop an efficient alternating direction method of multipliers (ADMM)-based algorithm. Extensive experiments on real-world applications collectively verify that TRKPCA achieves superiority over the state-of-the-art RPCA methods.

Progress of studies on natural products for glioblastoma therapy.

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.

ß-acetoxyisovalerylalkannin suppresses proliferation and induces ROS-based mitochondria-mediated apoptosis in human melanoma cells.

ß-acetoxyisovalerylalkannin (ß-AIVA) is one of shikonin/alkannin derivative, which were mainly extracted from Boraginaceae family. The effects of ß-AIVA on human melanoma A375 cells and U918 cells were investigated in vitro. The CCK-8 assay showed that ß-AIVA inhibited proliferation of cells. Results from flow cytometry, ROS assay and JC-1 assay showed that ß-AIVA increased late apoptosis rate, induced the production of ROS and promoted mitochondrial depolarization in cells. ß-AIVA regulated expressions of BAX and Bcl-2 proteins, and increased the expression of cleaved caspase-9 and cleaved caspase-3. These findings suggest that ß-AIVA may be a potential therapeutic drug for treating melanoma.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.

Diverse terpenoid glycosides with in vitro cytotoxicity from Glechoma longituba.

Terpenoids are the largest class of all known natural products, possessing structural diversity and numerous biological activities. Ten previously undescribed terpenoid glycosides, glechlongsides A-J (1-10), were isolated from the ethanol extract of the whole plant of Glechoma longituba, including diterpenoid glycoside and pentacyclic triterpenoid saponin. The structures of these compounds were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra. In addition, glechlongsides F-I (6-9) exhibited weak cytotoxicity against human cancer cell lines BGC-823, Be1, HCT-8, A2780, and A549 with IC50 values ranging from 3.77 to 30.95 µM, respectively.

Effect of Third Interstitial Fluid on Adverse Outcomes in Patients with Severe Pre-eclampsia and Twin Pregnancy: A 5-year Single-center Retrospective Study.

OBJECTIVE: This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia, and explore the differences in bad ending between twins and singletons. METHODS: The present retrospective cohort study was conducted on patients with severe pre-eclampsia, who delivered in Tongji Hospital, Wuhan, China, between 2017 and 2022. The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated. Then, the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid. RESULTS: A total of 709 patients were included for the present study. Among these patients, 68 patients had twin pregnancies, and 641 patients had singleton pregnancies. The rate of postpartum hemorrhage (2.81% vs. 13.24%, P<0.001), and admission rate to the Neonatal Intensive Care Unit (NICU) after birth (30.73% vs. 63.24%, P=0.011) were significantly higher in twin pregnancies. The neonatal weight of twins was statistically lower than singletons (1964.73±510.61 g vs. 2142.92±731.25 g, P=0.008). For the groups with the third interstitial fluid, the delivery week (P=0.001) and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group, when compared to singleton pregnancy group (P=0.032), and the length of hospital stay was shorter (P=0.044). Furthermore, there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid. CONCLUSION: The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies, when compared to singleton pregnancies. Thus, when patients develop the third interstitial fluid, twin pregnancies would more likely lead to adverse fetal outcomes, when compared to singleton pregnancies, and there would be no significant difference in maternal adverse outcomes. More attention should be given to patients who merge with the third interstitial fluid.

HDACs alters negatively to the tumor immune microenvironment in gynecologic cancers.

The role of histone deacetylases (HDACs) in the tumor immune microenvironment of gynecologic tumors remains unexplored. We integrated data from The Cancer Genome Atlas and Human Protein Atlas to examine HDAC expression in breast, cervical, ovarian, and endometrial cancers. Elevated HDAC expression correlated with poor prognosis and highly malignant cancer subtypes. Gene Set Enrichment Analysis revealed positive associations between HDAC expression and tumor proliferation signature, while negative associations were found with tumor inflammation signature. Increased HDAC expression was linked to reduced infiltration of natural killer (NK), NKT, and CD8+ T cells, along with negative associations with the expression of PSMB10, NKG7, CCL5, CD27, HLA-DQA1, and HLA-DQB1. In a murine 4T1 breast cancer model, treatment with suberoylanilide hydroxamic acid (SAHA; HDAC inhibitor) and PD-1 antibody significantly inhibited tumor growth and infiltration of CD3+ and CD8+ T cells. Real-time polymerase chain reaction revealed upregulated expressions of Psmb10, Nkg7, Ccl5, Cd8a, Cxcr6, and Cxcl9 genes, while Ctnnb1 and Myc genes were inhibited, indicating tumor suppression and immune microenvironment activation. Our study revealed that HDACs play tumor-promoting and immunosuppressive roles in gynecologic cancers, suggesting HDAC inhibitors as potential therapeutic agents for these cancers.

Achieving Practical Venue Recycle of Waste Oil-Based Drilling Fluids with Vacuum Distillation Technology.

Drilling fluids are essential operating additives for extracting oil and shale gas. Thus, their pollution control and recycling utilization are significant to petrochemical development. Vacuum distillation technology was used in this research to handle waste oil-based drilling fluids and achieve reutilization. Briefly, recycled oil and recovered solids can be obtained from waste oil-based drilling fluids whose density is 1.24-1.37 g/cm3 by vacuum distillation under the condition of an external heat transfer oil temperature of 270 ± 5 °C and a reaction pressure below 5 × 103 Pa. Meanwhile, recycled oil has excellent apparent viscosity (AV, 21 mPa·s) and plastic viscosity (PV, 14 mPa·s), which could be used as a substitute for 3# white oil. Furthermore, PF-ECOSEAL prepared by recycled solids exhibited better rheological properties (27.5 mPa·s AV, 18.5 mPa·s PV, and 9 Pa yield point) and plugging performance (32 mL V0, 1.90 mL/min1/2Vsf) than drilling fluids prepared with the conventional plugging agent PF-LPF. Our work confirmed that vacuum distillation is a valid technology in innocuity treatment and resource utilization of drilling fluids and has great value in industrial applications.

Understanding the 0++ and 2++ charmonium(-like) states near 3.9 GeV.

We propose that the X(3915) observed in the J/ψω channel is the same state as the χc2(3930), and the X(3960), observed in the Ds+Ds- channel, is an S-wave Ds+Ds- hadronic molecule. In addition, the JPC=0++ component in the B+→D+D-K+ assigned to the X(3915) in the current Review of Particle Physics has the same origin as the X(3960), which has a mass around 3.94 GeV. To check the proposal, the available data in the DD¯ and Ds+Ds- channels from both B decays and γγ fusion reaction are analyzed considering both the DD¯-DsD¯s-D*D¯*-Ds*D¯s* coupled channels with 0++ and a 2++ state introduced additionally. It is found that all the data in different processes can be simultaneously well reproduced, and the coupled-channel dynamics produce four hidden-charm scalar molecular states with masses around 3.73, 3.94, 3.99 and 4.23 GeV, respectively. The results may deepen our understanding of the spectrum of charmonia as well as of the interactions between charmed hadrons.

The role of lncRNA SNHG14 in gastric cancer: enhancing tumor cell proliferation and migration, and mechanisms of CDH2 expression.

LncRNAs are a class of non-coding RNAs that play an important role in regulating gene expression. However, their specific molecular mechanisms in gastric carcinogenesis and metastasis need further exploration. TCGA data showed that the expression of MFGE8, which was closely related to survival, was significantly positively correlated with lncRNA SNHG14. And moreover, the results of high-throughput sequencing and qRT-PCR showed that lncRNA SNHG14 was significantly elevated in gastric cancer. Further, in vitro functional realization showed that lncRNA SNHG14 overexpression significantly increased gastric cancer's proliferation, invasion and migration. Animal experiments also showed that lncRNA SNHG14 overexpression promoted tumorigenesis and metastasis in vivo. Mechanistically, MFGE8 activates the expression of lncRNA SNHG14, which activates the cellular EMT by stabilizing CDH2. Our study suggests that lncRNA SNHG14 could be a potential target for gastric cancer therapy.

Gastric cancer is one of the malignant tumors with a high incidence and high mortality rate worldwide. The current treatment modalities for gastric cancer are surgery, chemotherapy and targeted therapy. However, the 5-year survival rate of gastric cancer patients is still less than 30%. The main reason for the low survival rate of gastric cancer patients is that most cases are already at an advanced disease stage when first diagnosed, with tumor metastasis, tumor heterogeneity and resistance to radiotherapy. TCGA data showed that the expression of MFGE8, which was closely related to survival, was significantly positively correlated with lncRNA SNHG14.We found that lncRNA SNHG14 expression was significantly elevated in gastric cancer by high-throughput sequencing. It was further confirmed in vitro and in vivo that overexpression of lncRNA SNHG14 promoted the proliferation and migration ability of gastric cancer. Mechanistically, lncRNA SNHG14 played an oncogene role by promoting CDH2 expression to activate EMT in tumor cells.

Ir-Catalyzed Chemo-, Regio-, and Enantioselective Allylic Enolization of 6,6-Dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one Involving Keto-Enol Isomerization.

The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.

Prediction of a Narrow Exotic Hadronic State with Quantum Numbers J

Lots of charmonium-like structures have been observed in the last two decades. Most of them have quantum numbers that can be formed by a pair of charm and anticharm quarks, thus it is difficult to unambiguously identify the exotic ones among them. In this Letter, by exploiting heavy quark spin symmetry, we present a robust prediction of the hadronic molecular scenario, where the ψ(4230), ψ(4360) and ψ(4415) are identified as DD[over ¯]_{1}, D^{*}D[over ¯]_{1}, and D^{*}D[over ¯]_{2}^{*} bound states, respectively. We show that a flavor-neutral charmonium-like exotic state with quantum numbers J^{PC}=0^{--}, denoted as ψ_{0}(4360), should exist as a D^{*}D[over ¯]_{1} bound state. The mass and width of the ψ_{0}(4360) are predicted to be (4366±18) MeV and less than 10 MeV, respectively. The ψ_{0}(4360) is significant in two folds: no 0^{--} hadron has been observed so far, and a study of this state will enlighten the understanding of the mysterious vector mesons between 4.2 and 4.5 GeV, as well as the nature of previously observed exotic Z_{c} and P_{c} states. We propose that such an exotic state can be searched for in e^{+}e^{-}→ηψ_{0}(4360) and uniquely identified by measuring the angular distribution of the outgoing η meson.

Adenosine-A2A Receptor Signaling Plays a Crucial Role in Sudden Unexpected Death in Epilepsy.

Adenosinergic activities are suggested to participate in SUDEP pathophysiology; this study aimed to evaluate the adenosine hypothesis of SUDEP and specifically the role of adenosine A2A receptor (A2AR) in the development of a SUDEP mouse model with relevant clinical features. Using a combined paradigm of intrahippocampal and intraperitoneal administration of kainic acid (KA), we developed a boosted-KA model of SUDEP in genetically modified adenosine kinase (ADK) knockdown (Adk+/-) mice, which has reduced ADK in the brain. Seizure activity was monitored using video-EEG methods, and in vivo recording of local field potential (LFP) was used to evaluate neuronal activity within the nucleus tractus solitarius (NTS). Our boosted-KA model of SUDEP was characterized by a delayed, postictal sudden death in epileptic mice. We demonstrated a higher incidence of SUDEP in Adk+/- mice (34.8%) vs. WTs (8.0%), and the ADK inhibitor, 5-Iodotubercidin, further increased SUDEP in Adk+/- mice (46.7%). We revealed that the NTS level of ADK was significantly increased in epileptic WTs, but not in epileptic Adk+/- mutants, while the A2AR level in NTS was increased in epileptic (WT and Adk+/-) mice vs. non-epileptic controls. The A2AR antagonist, SCH58261, significantly reduced SUDEP events in Adk+/- mice. LFP data showed that SCH58261 partially restored KA injection-induced suppression of gamma oscillation in the NTS of epileptic WT mice, whereas SCH58261 increased theta and beta oscillations in Adk+/- mutants after KA injection, albeit with no change in gamma oscillations. These LFP findings suggest that SCH58261 and KA induced changes in local neuronal activities in the NTS of epileptic mice. We revealed a crucial role for NTS A2AR in SUDEP pathophysiology suggesting A2AR as a potential therapeutic target for SUDEP risk prevention.

Nonlinear elasticity, yielding, and entropy in amorphous solids.

The holographic duality has proven successful in linking seemingly unrelated problems in physics. Recently, intriguing correspondences between the physics of soft matter and gravity are emerging, including strong similarities between the rheology of amorphous solids, effective field theories for elasticity, and the physics of black holes. However, direct comparisons between theoretical predictions and experimental/simulation observations remain limited. Here, we study the effects of nonlinear elasticity on the mechanical and thermodynamic properties of amorphous materials responding to shear, using effective field and gravitational theories. The predicted correlations among the nonlinear elastic exponent, the yielding strain/stress, and the entropy change due to shear are supported qualitatively by simulations of granular matter models. Our approach opens a path toward understanding the complex mechanical responses of amorphous solids, such as mixed effects of shear softening and shear hardening, and offers the possibility to study the rheology of solid states and black holes in a unified framework.

Preclinical characterization of the novel anti-SIRPα antibody BR105 that targets the myeloid immune checkpoint.

BACKGROUND: The CD47-SIRPα pathway acts as an important myeloid cell immune checkpoint and targeting the CD47/SIRPα axis represents a promising strategy to promote antitumor immunity. Several CD47-targeting agents show encouraging early activity in clinical trials. However, due to ubiquitous expression of CD47, the antigen sink and hematologic toxicity, such as anemia and thrombocytopenia, are main problems for developing CD47-targeting therapies. Considering the limited expression of SIRPα, targeting SIRPα is an alternative approach to block the CD47-SIRPα pathway, which may result in differential efficacy and safety profiles. METHODS: SIRPα-targeting antibody BR105 was generated by hybridoma fusion and following humanization. BR105 was characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. The functional activity was determined in in vitro phagocytosis assays by using human macrophages. The effect of BR105 on human T cell activation was studied using an OKT3-induced T-cell proliferation assay and an allogeneic mixed lymphocyte reaction. Human SIRPα-humanized immunodeficient mice were used in cancer models for evaluating the in vivo antitumor efficacy of BR105. Safety was addressed in a repeat-dose toxicity study in cynomolgus monkeys, and toxicokinetic analysis was further evaluated. RESULTS: BR105 shows broad binding activity across various SIRPα variants, and potently blocks the interaction of SIRPα and CD47. In vitro functional assays demonstrated that BR105 synergizes with therapeutic antibodies to promote phagocytosis of tumor cells. Moreover, the combination of BR105 and therapeutic antibody significantly inhibits tumor growth in a xenograft tumor model. Although BR105 may slightly bind to SIRPγ, it does not inhibit T cell activation, unlike other non-selective SIRPα-targeting antibody and CD47-targeting agents. Toxicity studies in non-human primates show that BR105 is well tolerated with no treatment-related adverse effects noted. CONCLUSIONS: The novel and differentiated SIRPα-targeting antibody, BR105, was discovered and displays promising antitumor efficacy in vitro and in vivo. BR105 has a favorable safety profile and shows no adverse effects on T cell functionality. These data support further clinical development of BR105, especially as a therapeutic agent to enhance efficacy when used in combination with tumor-targeting antibodies or antibodies that target other immune checkpoints.

Prenylaromadendrane-type diterpenoids from the gum resin of Boswellia sacra flueck and their cytotoxic effects.

Two new prenylaromadendrane-type diterpenoids, and three known analogues, were isolated from the ethanol extract of the gum resin of B. sacra Flueck. The structures of the new compounds were elucidated using 1 D and 2 D NMR spectroscopic analyses, mass spectrometric data, circular dichroism spectra, and comparison with the other compounds in the literature. One diterpenoid represents the first example of an acetoxyl-substituted prenylaromadendranoid in frankincense. All compounds exhibited notable cytotoxicity against human malignant glioma (U87-MG) cell line, with inhibitory rates exceeding that of the positive control 5-fluorouracil. However, nitric oxide inhibition induced by lipopolysaccarides was not observed in primary mouse peritoneal macrophages.

Four new polyprenylated acylphloroglucinol derivatives from Hypericum beanii.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (1-2), and two new biosynthetic precursors, hyperbeanins R-S (3-4), were isolated from Hypericum beanii, together with three known analogs (5-7). Compound 1 was one of type A PPAPs featured with unusual bicyclo[5.3.1]hendecane core. The structures of isolates were established by NMR spectroscopic methods, experimental electronic circular dichroism (ECD) spectra and comparisons with known compounds. Compounds 5 and 6 showed obvious hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage.

Isolation, physicochemical, and structure-function relationship of the hydrophobic variant of Fc-fusion proteins that bind to TNF-α receptor, HS002 and HS002A.

HS002 is the recombinant human tumor necrosis factor-α receptor Ⅱ: IgG Fc fusion protein licensed in China to treat rheumatism and psoriasis. The aim of this study was to isolate and characterize the hydrophobic freeze-dried powder injection (HS002) and ampoule injection (HS002A) variants derived from proteins of the same sequence and then to explore the structure-function relationship. Extensive physicochemical and structural testing was performed during a side-by-side comparison of the monomer peak and variant. Then the TNF-α-related binding activity, cell biological activity and affinity with FcRn were analyzed. Finally, a transformation study of the hydrophobic variant was performed under serum-like redox conditions. This research revealed that HS002A has similar physicochemical and structure-function relationship profiles to those of HS002. The hydrophobic variant exhibited the presence of new incorrect disulfide bridging. At the same time, this novel disulfide scrambled species structure-function relationship was found to be the molecular basis for reduced TNF-α binding and cell biological activities. In addition, incorrect disulfide bridging was found to be reversible under serum-like redox conditions, restoring TNF-α binding and cell biological activities to almost normal levels, all of which indicate that the variant is probably irrelevant to clinical efficacy once the drug enters the bloodstream.

TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway.

BACKGROUND: Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics. METHODS: Atomic Force Microscope (AFM) was used to measure the Young's modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry. RESULTS: We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. CONCLUSIONS: These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy.