The phospholipid flippase ATP9A enhances macropinocytosis to promote nutrient starvation tolerance in hepatocellular carcinoma.

Macropinocytosis is an effective strategy to mitigate nutrient starvation. It can fuel cancer cell growth in nutrient-limited conditions. However, whether and how macropinocytosis contributes to the rapid proliferation of hepatocellular carcinoma cells, which frequently experience an inadequate nutrient supply, remains unclear. Here, we demonstrated that nutrient starvation strongly induced macropinocytosis in some hepatocellular carcinoma cells. It allowed the cells to acquire extracellular nutrients and supported their energy supply to maintain rapid proliferation. Furthermore, we found that the phospholipid flippase ATP9A was critical for regulating macropinocytosis in hepatocellular carcinoma cells and that high ATP9A levels predicted a poor outcome for patients with hepatocellular carcinoma. ATP9A interacted with ATP6V1A and facilitated its transport to the plasma membrane, which promoted plasma membrane cholesterol accumulation and drove RAC1-dependent macropinocytosis. Macropinocytosis inhibitors significantly suppressed the energy supply and proliferation of hepatocellular carcinoma cells characterised by high ATP9A expression under nutrient-limited conditions. These results have revealed a novel mechanism that overcomes nutrient starvation in hepatocellular carcinoma cells and have identified the key regulator of macropinocytosis in hepatocellular carcinoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Injectable and Microporous Microgel-Fiber Granular Hydrogel Loaded with Bioglass and siRNA for Promoting Diabetic Wound Healing.

Injectable hydrogels find extensive application in the treatment of diabetic wound healing. However, traditional bulk hydrogels are significantly limited due to their nano-porous structure, which obstructs cell migration and tissue infiltration. Moreover, regulating inflammation and matrix metalloproteinase -9 (MMP-9) expression in diabetic wounds is crucial for enhancing wound healing. This study marks the first instance of introducing an efficient, scalable, and simple method for producing microfiber-gel granules encapsulating bioceramics powders. Utilizing this method, an injectable microporous granular microgel-fiber hydrogel (MFgel) is successfully developed by assembling microgel-fibers made from hyaluronic acid (HA) and sodium alginate (SA) loaded with small interfering RNA (siRNA) and bioglass (BG) particles. Compared to traditional hydrogels (Tgel), MFgel possesses a highly interconnected network with micron-sized pores, demonstrating favorable properties for cell adhesion and penetration in in vitro experiments. Additionally, MFgel exhibits a higher compressive modulus and superior mechanical stability. When implanted subcutaneously in mice, MFgel promotes cellular and tissue infiltration, facilitating cell proliferation. Furthermore, when applied to skin defects in diabetic rats, MFgel not only effectively regulates inflammation and suppresses MMP-9 expression but also enhances angiogenesis and collagen deposition, thereby significantly accelerating diabetic wound healing. Taken together, this hydrogel possesses great potential in diabetic wound healing applications.

BOP1 confers chemoresistance of triple-negative breast cancer by promoting CBP-mediated ß-catenin acetylation.

Chemoresistance is a major obstacle to the treatment of triple-negative breast cancer (TNBC), which has a poor prognosis. Increasing evidence has demonstrated the essential role of cancer stem cells (CSCs) in the process of TNBC chemoresistance. However, the underlying mechanism remains unclear. In the present study, we report that block of proliferation 1 (BOP1) serves as a key regulator of chemoresistance in TNBC. BOP1 expression was significantly upregulated in chemoresistant TNBC tissues, and high expression of BOP1 correlated with shorter overall survival and relapse-free survival in patients with TNBC. BOP1 overexpression promoted, while BOP1 downregulation inhibited the drug resistance and CSC-like phenotype of TNBC cells in vitro and in vivo. Moreover, BOP1 activated Wnt/ß-catenin signaling by increasing the recruitment of cyclic AMP response element-binding protein (CBP) to ß-catenin, enhancing CBP-mediated acetylation of ß-catenin, and increasing the transcription of downstream stemness-related genes CD133 and ALDH1A1. Notably, treating with the ß-catenin/CBP inhibitor PRI-724 induced an enhancement of chemotherapeutic response of paclitaxel in BOP1-overexpressing TNBC cells. These findings indicate that BOP1 is involved in chemoresistance development and might serve as a prognostic marker and therapeutic target in TNBC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Impaired interaural correlation processing in people with schizophrenia.

Detection of transient changes in interaural correlation is based on the temporal precision of the central representations of acoustic signals. Whether schizophrenia impairs the temporal precision in the interaural correlation process is not clear. In both participants with schizophrenia and matched healthy-control participants, this study examined the detection of a break in interaural correlation (BIC, a change in interaural correlation from 1 to 0 and back to 1), including the longest interaural delay at which a BIC was just audible, representing the temporal extent of the primitive auditory memory (PAM). Moreover, BIC-induced electroencephalograms (EEGs) and the relationships between the early binaural psychoacoustic processing and higher cognitive functions, which were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), were examined. The results showed that compared to healthy controls, participants with schizophrenia exhibited poorer BIC detection, PAM and RBANS score. Both the BIC-detection accuracy and the PAM extent were correlated with the RBANS score. Moreover, participants with schizophrenia showed weaker BIC-induced N1-P2 amplitude which was correlated with both theta-band power and inter-trial phase coherence. These results suggested that schizophrenia impairs the temporal precision of the central representations of acoustic signals, affecting both interaural correlation processing and higher-order cognitions.

Improving the Performance of Continuous-Variable Measurement-Device-Independent Quantum Key Distribution via a Noiseless Linear Amplifier.

In the continuous variable measurement-device-independent quantum key distribution (CV-MDI-QKD) protocol, both Alice and Bob send quantum states to an untrusted third party, Charlie, for detection through the quantum channel. In this paper, we mainly study the performance of the CV-MDI-QKD system using the noiseless linear amplifier (NLA). The NLA is added to the output of the detector at Charlie's side. The research results show that NLA can increase the communication distance and secret key rate of the CV-MDI-QKD protocol. Moreover, we find that the more powerful the improvement of the performance with the longer gain of NLA and the optimum gain is given under different conditions.

Management of elbow dysfunction associated with giant cell tumor of the distal humerus: achieving oncologic safety and good function by a combined reconstruction.

BACKGROUND: The purpose of our study was to evaluate the functional outcomes and oncologic results of elbow salvage surgery using arthrolysis combined with ligament repair and external fixation for reconstruction of the elbow after tumor excision and autografting. METHODS: We retrospectively reviewed 6 patients with elbow dysfunction associated with giant cell tumor of the distal humerus. All patients were treated with our combined protocol. We assessed the Musculoskeletal Tumor Society system score, range of motion, Mayo Elbow Performance Score, recurrence, and complications for each patient. RESULTS: The mean follow-up period was 48 months (range, 36-60 months). There were no cases of postoperative fracture, infection, elbow dislocation, elbow stiffness, or local recurrence. The average Musculoskeletal Tumor Society score was 28 of 30 points (93%; range, 87%-100%). The Mayo Elbow Performance Score improved from a mean of 61 points to 93 points, with mean flexion of 135° and mean extension of 3°. CONCLUSIONS: Local tumor resection, autografting, and elbow reconstruction by arthrolysis combined with ligament repair and external fixation can be performed with oncologic safety and provide satisfactory functional outcomes with low complication rates.

Speaking rhythmically improves speech recognition under "cocktail-party" conditions.

This study examines whether speech rhythm affects speech recognition under "cocktail-party" conditions. Against a two-talker masker, but not a speech-spectrum noise masker, recognition of the last (third) keyword in a normal rhythmic sentence was significantly better than that of the first keyword. However, this word-position-related speech-recognition improvement disappeared for rhythmically hybrid target sentences that were constructed by grouping parts from different sentences with different artificially modulated rhythms (rates) (fast, normal, or slow). Thus, the normal rhythm with a constant rate plays a role in improving speech recognition against informational speech masking, probably through a build-up of temporal prediction for target words.

Early cervical cancer impact of peritoneal vaginoplasty combined with laparoscopic radical hysterectomy improved sexual function.

OBJECTIVE: We investigated the impact of laparoscopic radical hysterectomy (LRH) in combination with peritoneal vaginoplasty (PV) in improving sexual function after radical hysterectomy (RH) in patients with early cervical cancer. METHODS: A total of 79 patients with early-stage cervical cancer younger than 45 years were assigned to receive LRH in combination with PV (the LRH-PV group; n = 31) or LRH alone (the LRH group; n = 48). Other 40 healthy females were selected as controls (the control group). The sexual function was assessed with Female Sexual Functioning Index (FSFI). The FSFI scores and sexual function in the postoperative 1 year were compared between the LRH-PV and LRH groups, LRH-PV and control groups, and LRH and control groups, respectively. RESULTS: Patients with LRH-PV showed significantly higher scores in sexual satisfaction, lubrication, pain, and total score than those with LRH alone (P < 0.05) but were not statistically different in scores regarding sexual desire, arousal, and orgasm (P > 0.05). Healthy controls showed the highest in total scores and 6 domains among all subjects. In addition, the FSFI total scores in the LRH-PV group, LRH group, and LRH-PV + LRH group were significantly decreased compared with the control (P < 0.05). CONCLUSIONS: Peritoneal vaginoplasty to lengthen the vagina improves sexual function of patients with early cervical cancer receiving LRH in sexual satisfaction, lubrication, and pain.

Multilevel evaluation of 'China Healthy Lifestyles for All', a nationwide initiative to promote lower intakes of salt and edible oil.

OBJECTIVE: To evaluate the impact of 'China Healthy Lifestyle for All' on levels of knowledge, taste and intentions to modify future consumption of salt and edible oil. METHODS: Between May and August 2012, a face-to-face survey carried out in all 31 provinces, autonomous regions, and municipalities in mainland China, achieved a 98.1% response. Intention-To-Treat analysis via multilevel logistic regression was used to examine differences in outcomes between 31,396 non-institutionalised individuals aged > 18 years from 31 'intervention' (i.e. participating) and 26 'control' (i.e. non-participating) counties respectively. RESULTS: Adjusting for socioeconomic confounders, participants in 'intervention' counties were more likely to know the limit of salt (Odds Ratio 3.14, 95% Confidence Interval (95% CI) 1.98, 4.96) and oil consumption (3.67, 95% CI 2.31, 5.82), and were more intent to modify their consumption (salt 1.98, 95% CI 1.41, 2.76; oil OR 1.99, 95% CI 1.41, 2.81) and to report a change in taste (salt 1.90, 95% CI 1.31, 2.75; oil 2.07, 95% CI 1.38, 3.10). 'Intervention' effects were consistent regardless of income or education, but women and older participants benefited disproportionately. Outcomes were 2.8 and 4.7 times more likely among those with better recall. CONCLUSION: Place-based health promotion interventions have an important role to play in addressing non-communicable disease in China.

Analyzing simultaneous positive expression of EZH2 and P53 protein to improve predictive value in cervical squamous cell carcinoma.

OBJECTIVE: The current study was undertaken to investigate the predictive value of simultaneous enhancer of zeste homolog 2 (EZH2) and P53 expression in lesions of patients with cervical squamous cell carcinoma. METHODS: Quantum dot double fluorescence staining was applied to detect EZH2 and P53 protein in biopsy tissue of 168 patients with cervical squamous cell carcinoma. The expression was classified into double positive (EZH2 and P53 were positively expressed), single positive (either EZH2 or P53 was positively expressed), and double negative (neither was positively expressed). The EZH2 and P53 expression, clinical stages of cervical cancer, lymph node metastasis, progression-free survival, and overall survival were analyzed. RESULTS: A relationship of EZH2 and P53 expression with the clinical stage of cervical cancer and lymph node metastasis was indicated. Simultaneous detection of both proteins could partly predict prognosis, consistent with previous studies' results. The current study demonstrated that the expression levels of EZH2 and P53 in tumor tissue and the proportion of cases with double-positive expression significantly increased with increasing clinical stages of cancer, also confirming up-regulated expression of EZH2 and P53 with increasing stages. These findings may suggest that the 2 proteins were involved in the development of cervical cancer, but the nature of their interaction is undefined. The increase of EZH2 and P53 expression in patients with lymph node metastasis indicated that they may be involved in metastasis of cervical cancer. CONCLUSION: Simultaneous positive EZH2 and P53 expression could improve the predictive value of a poor prognosis in cervical cancer.

Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing.

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.

Prevalence and control of diabetes in Chinese adults.

IMPORTANCE: Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. OBJECTIVE: To investigate the prevalence of diabetes and glycemic control in the Chinese adult population. DESIGN, SETTING, AND PARTICIPANTS: Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. MAIN OUTCOMES AND MEASURES: Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control. RESULTS: The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control. CONCLUSIONS AND RELEVANCE: The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.

Reduced neural tracking of speech linguistic structures in children.

The adult brain can efficiently track both lower-level (i.e., syllable) and higher-level (i.e., phrase) linguistic structures to comprehend speech. When children actively or passively listened to speech, we found robust neural tracking of syllabic structure but marginally significant tracking of phrasal structure.

Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.

Human epidermal growth factor receptor 2-targeted (HER2-targeted) therapy is the mainstay of treatment for HER2+ breast cancer. However, the proteolytic cleavage of HER2, or HER2 shedding, induces the release of the target epitope at the ectodomain (ECD) and the generation of a constitutively active intracellular fragment (p95HER2), impeding the effectiveness of anti-HER2 therapy. Therefore, identifying key regulators in HER2 shedding might provide promising targetable vulnerabilities against resistance. In the current study, we found that upregulation of dolichyl-phosphate N-acetylglucosaminyltransferase (DPAGT1) sustained high-level HER2 shedding to confer trastuzumab resistance, which was associated with poor clinical outcomes. Upon trastuzumab treatment, the membrane-bound DPAGT1 protein was endocytosed via the caveolae pathway and retrogradely transported to the ER, where DPAGT1 induced N-glycosylation of the sheddase - ADAM metallopeptidase domain 10 (ADAM10) - to ensure its expression, maturation, and activation. N-glycosylation of ADAM10 at N267 protected itself from ER-associated protein degradation and was essential for DPAGT1-mediated HER2 shedding and trastuzumab resistance. Importantly, inhibition of DPAGT1 with tunicamycin acted synergistically with trastuzumab treatment to block HER2 signaling and reverse resistance. These findings reveal a prominent mechanism for HER2 shedding and suggest that targeting DPAGT1 might be a promising strategy against trastuzumab-resistant breast cancer.

Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon-To-Bone Healing.

Osteoporotic tendon-to-bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of the tendon, inflammatory microenvironment at the injury site, and the need for endogenous cell/tissue infiltration, there is an imminent need for an ideal scaffold to promote TBH that has aligned architecture, ability to modulate inflammation, and macroporous structure. Herein, a novel macroporous hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose-derived stem cells (sEVs) (MHA-sEVs) with aligned architecture and immunomodulatory ability is fabricated. When implanted subcutaneously, MHA-sEVs significantly improve cell infiltration and tissue integration through its macroporous structure. When applied to the osteoporotic RCR model, MHA-sEVs promote TBH by improving tendon repair through macroporous aligned architecture while enhancing bone regeneration by modulating inflammation. Notably, the biomechanical strength of MHA-sEVs is approximately two times higher than the control group, indicating great potential in reducing postoperative retear rates. Further cell-hydrogel interaction studies reveal that the alignment of microfiber gels in MHA-sEVs induces tenogenic differentiation of tendon-derived stem cells, while sEVs improve mitochondrial dysfunction in M1 macrophages (Mφ) and inhibit Mφ polarization toward M1 via nuclear factor-kappaB (NF-κb) signaling pathway. Taken together, MHA-sEVs provide a promising strategy for future clinical application in promoting osteoporotic TBH.

BAG2 drives chemoresistance of breast cancer by exacerbating mutant p53 aggregate.

Rationale: Chemoresistance is a major challenge in the clinical management of patients with breast cancer. Mutant p53 proteins tend to form aggregates that promote tumorigenesis in cancers. We here aimed to explore the mechanism for the generation of mutant p53 aggregates in breast cancer and assess its role in inducing chemoresistance. Methods: Expression of BCL2-associated athanogene 2 (BAG2) was evaluated by qRT-PCR, western blotting, and immunohistochemistry in breast cancer patient specimens. The significance of BAG2 expression in prognosis was assessed by Kaplan-Meier survival analysis and the Cox regression model. The roles of BAG2 in facilitating the formation of mutant p53 aggregates were analyzed by co-immunoprecipitation, immunofluorescence, and semi-denaturing detergent-agarose gel electrophoresis assays. The effects of BAG2 on the chemoresistance of breast cancer were demonstrated by cell function assays and mice tumor models. Results: In the present study, we found that BAG2 was significantly upregulated in relapse breast cancer patient tissues and high BAG2 was associated with a worse prognosis. BAG2 localized in mutant p53 aggregates and interacted with misfolded p53 mutants. BAG2 exacerbated the formation of the aggregates and recruited HSP90 to promote the propagation and maintenance of the aggregates. Consequently, BAG2-mediated mutant p53 aggregation inhibited the mitochondrial apoptosis pathway, leading to chemoresistance in breast cancer. Importantly, silencing of BAG2 or pharmacological targeting of HSP90 substantially reduced the aggregates and increased the sensitivity of chemotherapy in breast cancer. Conclusion: These findings reveal a significant role of BAG2 in the chemoresistance of breast cancer via exacerbating mutant p53 aggregates and suggest that BAG2 may serve as a potential therapeutic target for breast cancer patients with drug resistance.

Sensitivity to a break in interaural correlation is co-modulated by intensity level and interaural delay.

This study investigated whether sound intensity affects listeners' sensitivity to a break in interaural correlation (BIC) embedded in wideband noise at different interaural delays. The results show that the detection duration threshold remained stable at the intensity between 60 and 70 dB SPL, but increased in accelerating fashion as the intensity decreased toward 40 dB SPL. Moreover, the threshold elevated linearly as the interaural delay increased from 0 to 4 ms, and the elevation slope became larger as the intensity decreased from 50 to 40 dB SPL. Thus, detecting the BIC is co-modulated by both intensity and interaural delay.

Classification and detection of COVID-19 X-Ray images based on DenseNet and VGG16 feature fusion.

Since December 2019, the novel coronavirus disease (COVID-19) caused by the syndrome coronavirus 2 (SARS-CoV-2) strain has spread widely around the world and has become a serious global public health problem. For this high-speed infectious disease, the application of X-ray to chest diagnosis plays a key role. In this study, we propose a chest X-ray image classification method based on feature fusion of a dense convolutional network (DenseNet) and a visual geometry group network (VGG16). This paper adds an attention mechanism (global attention machine block and category attention block) to the model to extract deep features. A residual network (ResNet) is used to segment effective image information to quickly achieve accurate classification. The average accuracy of our model in detecting binary classification can reach 98.0%. The average accuracy for three category classification can reach 97.3%. The experimental results show that the proposed model has good results in this work. Therefore, the use of deep learning and feature fusion technology in the classification of chest X-ray images can become an auxiliary tool for clinicians and radiologists.

Subjective tinnitus patients with normal pure-tone hearing still suffer more informational masking in the noisy environment.

Subjective tinnitus patients experience more hearing difficulties than normal peers in complex hearing environments, even though most of these patients have normal pure-tone hearing thresholds. Using speech recognition tasks under different masking conditions can provide insight into whether the effects of tinnitus are lateralized and the mechanisms behind the effects. By simulating sound field recordings, we obtain a target speech sentence that can be perceived as presented on one side and noise or speech masking with or without spatial separation from it. Our study used the virtual sound field technique to investigate the difference in speech recognition ability between chronic subjective tinnitus patients and a normal-hearing control group under the four masking conditions (speech-spectrum noise masking or two-talker speech masking, with or without perceived spatial separation). Experiment 1 showed no differences for target speech perceived location (left or right), which rules out a lateralization of the effect of tinnitus patients. Experiment 2 further found that although tinnitus patients had weaker performance than normal people in very complex auditory scenarios, when the spatial cue of the target speech exists, they can make good use of this cue to make up for the original processing disadvantage and achieve a similar performance as the normal-hearing group. In addition, the current study distinguished the effects of informational masking and energetic masking on speech recognition in patients with tinnitus and normal hearing. The results suggest that the impact of tinnitus on speech recognition in patients is more likely to occur in the auditory center rather than the periphery.

HMMR promotes peritoneal implantation of gastric cancer by increasing cell-cell interactions.

BACKGROUND: Distant metastasis is the prominent factor for cancer-induced death of gastric cancer in which peritoneum is one of the dominating targets of gastric cancer metastasis. However, there is still a lack of effective predictive indicators and treatment methods for gastric cancer patients with peritoneal metastasis. METHODS: A clustering assay was used to investigate the cell aggregates formation ability. While the soft agar assay and anoikis assay were performed to detect the anchorage-independent growth and anoikis-resistant ability respectively. Luciferase activity assay, western blotting and immunofluorescence were used to explore the effect of HMMR on AKT signaling activity. The peritoneal implantation model was examined to explore the role of HMMR in vivo. RESULTS: Silencing of HMMR expression markedly reduced the peritoneal metastasis of gastric cancer cells through reducing cell-cell interactions. Mechanistically, HA-HMMR could activate Akt signaling, thus succeeding in distant colonization and metastatic outgrowth. Importantly, inducible depletion of HMMR significantly abrogates peritoneal implantation of gastric cancer in vitro and in vivo. CONCLUSION: Our study highlights that HMMR promotes peritoneal implantation of gastric cancer. A better understanding of HMMR's functions and mechanism might provide a novel therapeutic target and prognostic marker for metastatic gastric cancer.