Targeting estrogen mediated CYP4F2/CYP4F11-20-HETE metabolic disorder decelerates tumorigenesis in ER+ breast cancer.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

CgNis1's Impact on Virulence and Stress Response in Colletotrichum gloeosporioides.

Pepper anthracnose caused by Colletotrichum gloeosporioides infection is an important fungal disease and represents a serious threat to pepper yield and quality. At present, the pathogenic molecular mechanism of C. gloeosporioides is not very clear. In our study, we characterized the function of C. gloeosporioides CgNis1, a homolog of Magnaporthe oryzae MoNis1. We found that the ∆Cgnis1 mutant reduced the growth rate and was defective in conidiation. Although the rate of appressorium formation was unaffected, the germ tube was found to be abnormal. CgNis1 was shown to be involved in the H2O2 stress response and maintaining cell membrane permeability. The pathogenicity assays performed in this study indicated that the deletion of CgNIS1 is associated with virulence. Our results indicate that CgNis1 is necessary for the growth, development, and pathogenicity of the fungus. This work provides an in-depth analysis of the Nis1 protein, helps to enhance studies on pathogen-related molecular mechanisms, and provides a theoretical basis for the prevention and control of C. gloeosporioides in peppers.

Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study.

Background: Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods: Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [ß-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results: Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in ß-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions: Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

Short-term and long-term outcomes after robotic versus open hepatectomy in patients with large hepatocellular carcinoma: a multicenter study.

BACKGROUND: Robotic hepatectomy (RH) is currently widely accepted and it is associated with some benefits when compared to open hepatectomy (OH). However, whether such benefits can still be achieved for patients with large hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the short-term and long-term outcomes of patients undergoing RH or OH. METHODS: Perioperative and survival data from patients with large HCC who underwent RH or OH between January 2010 and December 2020 were collected from eight centres. Propensity score matching (PSM) was performed to minimise potential biases. RESULTS: Using predefined inclusion criteria, 797 patients who underwent OH and 309 patients who underwent RH were enroled in this study. After PSM, 280 patients in the robotic group had shorter operative time (median 181 vs. 201 min, P <0.001), lower estimated blood loss (median 200 vs. 400 ml, P <0.001), and shorter postoperative length of stay (median 6 vs. 9 days, P <0.001) than 465 patients in the open group. There were no significant differences between the two groups in overall survival and recurrence-free survival. Cox analysis showed AFP greater than 400 ng/ml, tumour size greater than 10 cm, and microvascular invasion were independent risk factors for overall survival and recurrence-free survival. After PSM, subgroup analysis showed that patients with a huge HCC (diameter >10 cm) who underwent RH had significantly lower estimated blood loss (median 200.0 vs. 500.0 min, P <0.001), and shorter length of stay (median 7 vs. 10 days, P <0.001) than those who underwent OH. CONCLUSION: Safety and feasibility of RH and OH for patients with large HCC were comparable. RH resulted in similar long-term survival outcomes as OH.

LLDT-8 ameliorates experimental autoimmune encephalomyelitis by mediating macrophage functions in the priming stage.

Multiple sclerosis (MS) is an inflammatory demyelinating disease in the central nervous system caused by T cell activation mediated by peripheral macrophages, resulting in severe neurological deficits and disability. Due to the currently limited and expensive treatments for MS, we here introduce an economic Chinese medicine extract, (5R)-5-Hydroxytriptolide (LLDT-8), which shows low toxicity and high immunosuppressive activity. We used the widely accepted mouse model of MS, experimental autoimmune encephalomyelitis (EAE), to examine the immunosuppressive effect of LLDT-8 in vivo. Through the RNA-sequence analysis of peripheral macrophages in EAE mice, we discovered that LLDT-8 alleviates the symptoms of EAE by inhibiting the proinflammatory effect of macrophages, thereby blocking the activation and proliferation of T cells. In all, we found that LLDT-8 could be a potential treatment for MS.

A review on the mechanisms underlying the antitumor effects of natural products by targeting the endoplasmic reticulum stress apoptosis pathway.

Cancer poses a substantial risk to human life and wellbeing as a result of its elevated incidence and fatality rates. Endoplasmic reticulum stress (ERS) is an important pathway that regulates cellular homeostasis. When ERS is under- or overexpressed, it activates the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-, inositol-requiring enzyme 1 (IRE1)- and activating transcription Factor 6 (ATF6)-related apoptotic pathways to induce apoptosis. Tumor cells and microenvironment are susceptible to ERS, making the modulation of ERS a potential therapeutic approach for treating tumors. The use of natural products to treat tumors has substantially progressed, with various extracts demonstrating antitumor effects. Nevertheless, there are few reports on the effectiveness of natural products in inducing apoptosis by specifically targeting and regulating the ERS pathway. Further investigation and elaboration of its mechanism of action are still needed. This paper examines the antitumor mechanism of action by which natural products exert antitumor effects from the perspective of ERS regulation to provide a theoretical basis and new research directions for tumor therapy.

Synergistic effects of a carbon emissions trading scheme on carbon emissions and air pollution: The case of China.

Facing the dual pressures of the exacerbation of global climate change and the deterioration of the domestic environment caused by pollution, China has clearly adopted environmental regulatory measures to improve the climate environment. One measure is the carbon emissions trading scheme (CETS), which serves as a notable example of the country's efforts to improve the climate environment. We gathered panel data from 285 prefecture-level cities in China from 2005 to 2018 and used the Difference-in-Differences (DID) model to empirically examine the synergistic effects of the CETS on carbon emissions and air pollution. The results indicate that CETS have been effective in reducing urban carbon emissions by approximately 9.8%. Additionally, the schemes have caused a simultaneous reduction in particulate matter (PM)2.5 emissions by 11.7% and sulfur dioxide (SO2 ) emissions by approximately 9.7%, mitigating urban air pollution in China. It demonstrates that the scheme has significant synergistic effects on carbon emissions and air pollution. To achieve synergistic effects of CETS, effective measures include reducing energy intensity and upgrading the industrial structure. The implementation of CETS had heterogeneity in different conditions, and the synergistic effect of the scheme is more significant in eastern regions, large cities, and the final industrial stage. Our findings offer innovative solutions for the integrated management of carbon emissions and air pollution and provide valuable insights for policymakers to enhance China's CETS. Integr Environ Assess Manag 2023;00:1-13. © 2023 SETAC.

The energy conservation and emission reduction co-benefits of China's emission trading system.

Emission Trading System (ETS) is an innovative practice under the progress of green development in China. It is also an important method for China to achieve market-oriented environmental governance in ecological civilization construction. The ETS pilot policy has implemented for more than 10 years. However, the co-benefits of ETS pilot policy by the integration of energy consumption, carbon and sulfur dioxide emissions, and wastewater has not been evaluated. In order to fill this gap, we use the 2003-2017 annual data of 30 China's provinces (municipalities and autonomous regions), and utilize the Difference-in-Differences (DID) model and Propensity Score Matching (PSM-DID) methodology to evaluate the co-benefits of ETS pilot policy on energy conservation and emission reduction. We find that the ETS pilot policy significantly promote energy conservation and emission reduction. Eastern and central China have significantly benefited from the policy, while the western China has not due to the limited technology and innovation as well as an imbalance of the industrial structure. The results provide the policy reference for China's government and institutions as well as the governments and institutions around the world to fulfill their commitments to save energy and reduce emissions, and early achieve the carbon peaking and carbon neutralization.

Strain-Induced Structural Phase Transitions in Epitaxial (001) BiCoO3 Films: A First-Principles Study.

We have simulated BiCoO3 films epitaxially grown along (001) direction with density functional theory computations. Leading candidates for the lowest-energy phases have been identified. The tensile strains induce magnetic phase transition in the ground state (P4mm symmetry) from a C-type antiferromagnetic order to a G-type order for the in-plane lattice parameter above 3.922 Å. The G-type antiferromagnetic order will be maintained with larger tensile strains; however, a continuous structural phase transition will occur, combining the ferroelectric and antiferrodistortive modes. In particular, the larger tensile strain allows an isostructural transition, the so-called Cowley's ''Type Zero'' phase transitions, from Cc-(I) to Cc-(II), with a slight volume collapse. The orientation of ferroelectric polarization changes from the out-of-plane direction in the P4mm to the in-plane direction in the Pmc21 state under epitaxial tensile strain; meanwhile, the magnetic ordering temperature TN can be strikingly affected by the variation of misfit strain.

Magnesium Ingot Stacking Segmentation Algorithm for Industrial Robot Based on the Correction of Image Overexposure Area.

This paper proposes an adaptive threshold segmentation algorithm for the magnesium ingot stack based on image overexposure area correction (ATSIOAC), which solves the problem of mirror reflection on the surface of magnesium alloy ingots caused by external ambient light and auxiliary light sources. Firstly, considering the brightness and chromaticity information of the mapped image, we divide the exposure probability threshold into weak exposure and strong exposure regions. Secondly, the saturation difference between the magnesium ingot region and the background region is used to obtain a mask for the magnesium ingot region to eliminate interference from the image background. Then, the RGB average of adjacent pixels in the overexposed area is used as a reference to correct the colors of the strongly exposed and weakly exposed areas, respectively. Furthermore, in order to smoothly fuse the two corrected images, pixel weighted average (WA) is applied. Finally, the magnesium ingot sorting experimental device was constructed and the corrected top surface image of the ingot pile was segmented through ATSIOAC. The experimental results show that the overexposed area detection and correction algorithm proposed in this paper can effectively correct the color information in the overexposed area, and when segmenting ingot images, complete segmentation results of the top surface of the ingot pile can be obtained, effectively improving the accuracy of magnesium alloy ingot segmentation. The segmentation algorithm achieves a segmentation accuracy of 94.38%.

Can the development of renewable energy in China compensate for the damage caused by environmental pollution to residents' health?

China's rapid economic growth in recent decades has caused a growing problem of environmental pollution, which negatively impacts the physical and mental health of residents. In recent years, renewable energy has emerged as a promising solution to alleviate environmental pollution and improve residents' well-being. However, it is unknown whether renewable energy development can counterbalance the health impacts of environmental pollution. Therefore, we conducted a study using data from the China Family Panel Studies (CFPS) to examine the impact of environmental pollution and renewable energy on the health of 20,694 residents. Our analysis showed that renewable energy development can partially offset the negative health effects of environmental pollution. Specifically, we found that a 1% increase in environmental pollution is linked to an average decrease of 0.0911% in physical health (PHY) and 0.0566% in mental health (MEN), whereas each 1% rise in renewable energy corresponds to an average increase of 0.2585% in PHY and 0.1847% in MEN. These positive effects apply to male and female residents, urban and rural residents, young and middle-aged adults, and people with low, medium, and high levels of education. These findings are significant for decision-makers striving to improve Chinese residents' physical and mental health by considering the specific impact of renewable energy and comprehensive environmental pollution.

Glutaredoxin-1 promotes lymphangioleiomyomatosis progression through inhibiting Bim-mediated apoptosis via COX2/PGE2/ERK pathway.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease, characterized by progressive cyst formation and respiratory failure. Clinical treatment with the mTORC1 inhibitor rapamycin could relieve partially the respiratory symptoms, but not curative. It is urgent to illustrate the fundamental mechanisms of TSC2 deficiency to the development of LAM, especially mTORC1-independent mechanisms. Glutaredoxin-1 (Glrx), an essential glutathione (GSH)-dependent thiol-oxidoreductase, maintains redox homeostasis and participates in various processes via controlling protein GSH adducts. Redox signalling through protein GSH adducts in LAM remains largely elusive. Here, we demonstrate the underlying mechanism of Glrx in the pathogenesis of LAM. METHODS: 1. Abnormal Glrx expression in various kinds of human malignancies was identified by the GEPIA tumour database, and the expression of Glrx in LAM-derived cells was detected by real-time quantitative reverse transcription (RT-qPCR) and immunoblot. 2. Stable Glrx knockdown cell line was established to evaluate cellular impact. 3. Cell viability was determined by CCK8 assay. 4. Apoptotic cell number and intracellular reactive oxygen species (ROS) level were quantified by flow cytometry. 5. Cox2 expression and PGE2 production were detected to clarify the mechanism of Bim expression modulated by Glrx. 6. S-glutathionylated p65 was enriched and detected by immunoprecipitation and the direct regulation of Glrx on p65 was determined. 7. The xenograft animal model was established and photon flux was analyzed using IVIS Spectrum. RESULTS: In LAM, TSC2 negatively regulated abnormal Glrx expression and activation in a mTORC1-independent manner. Knockdown of Glrx increased the expression of Bim and the accumulation of ROS, together with elevated S-glutathionylated proteins, contributing to the induction of apoptotic cell death and inhibited cell proliferation. Knockdown of Glrx in TSC2-deficient LAM cells increased GSH adducts on nuclear factor-kappa B p65, which contributed to a decrease in the expression of Cox2 and the biosynthesis of PGE2. Inhibition of PGE2 metabolism attenuated phosphorylation of ERK, which led to the accumulation of Bim, due to the imbalance of its phosphorylation and proteasome degradation. In xenograft tumour models, knockdown of Glrx in TSC2-deficient LAM cells inhibited tumour growth and increased tumour cell apoptosis. CONCLUSIONS: Collectively, we provide a novel redox-dependent mechanism in the pathogenesis of LAM and propose that Glrx may be a beneficial strategy for the treatment of LAM or other TSC-related diseases.

Short-term outcomes of robotic versus open hepatectomy among overweight patients with hepatocellular carcinoma: a propensity score-matched study.

BACKGROUND: Robotic hepatectomy (RH) has gradually been accepted as it has overcome some of the limitations of open hepatectomy (OH). This study was to compare short-term outcomes in RH and OH for overweight (preoperative body mass index ≥ 25 kg/m²) patients with hepatocellular carcinoma (HCC). METHODS: Perioperative and postoperative data from these patients who underwent RH or OH between January 2010 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) analysis was performed to determine the impact of RH versus OH on the prognosis of overweight HCC patients. RESULTS: All 304 overweight HCC patients were included, 172 who were underwent RH, and 132 who were underwent OH. After the 1:1 PSM, there were 104 patients in both RH and OH groups. After PSM, the RH group of patients had a shorter operative time, less estimated blood loss (EBL), a longer total clamping time, a shorter postoperative length of stay (LOS), less chance of surgical site infection and less rates of blood transfusion (all P < 0.05) compared to the OH patients. The differences between operative time, EBL and LOS were more significant in obese patients. RH was found to be an independent protective factor of EBL ≥ 400ml relative to OH in overweight patients for the first time. CONCLUSIONS: RH was safe and feasible in overweight HCC patients. Compared with OH, RH has advantages in terms of operative time, EBL, postoperative LOS, and surgical site infection. Carefully selected overweight patients should be considered for RH.

Compound from Magnolia officinalis Ameliorates White Matter Injury by Promoting Oligodendrocyte Maturation in Chronic Cerebral Ischemia Models.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.

Multilevel effective surgical workflow recognition in robotic left lateral sectionectomy with deep learning: experimental research.

BACKGROUND: Automated surgical workflow recognition is the foundation for computational models of medical knowledge to interpret surgical procedures. The fine-grained segmentation of the surgical process and the improvement of the accuracy of surgical workflow recognition facilitate the realization of autonomous robotic surgery. This study aimed to construct a multigranularity temporal annotation dataset of the standardized robotic left lateral sectionectomy (RLLS) and develop a deep learning-based automated model for multilevel overall and effective surgical workflow recognition. METHODS: From December 2016 to May 2019, 45 cases of RLLS videos were enrolled in our dataset. All frames of RLLS videos in this study are labeled with temporal annotations. The authors defined those activities that truly contribute to the surgery as effective frames, while other activities are labeled as under-effective frames. Effective frames of all RLLS videos are annotated with three hierarchical levels of 4 steps, 12 tasks, and 26 activities. A hybrid deep learning model were used for surgical workflow recognition of steps, tasks, activities, and under-effective frames. Moreover, the authors also carried out multilevel effective surgical workflow recognition after removing under-effective frames. RESULTS: The dataset comprises 4 383 516 annotated RLLS video frames with multilevel annotation, of which 2 418 468 frames are effective. The overall accuracies of automated recognition for Steps, Tasks, Activities, and under-effective frames are 0.82, 0.80, 0.79, and 0.85, respectively, with corresponding precision values of 0.81, 0.76, 0.60, and 0.85. In multilevel effective surgical workflow recognition, the overall accuracies were increased to 0.96, 0.88, and 0.82 for Steps, Tasks, and Activities, respectively, while the precision values were increased to 0.95, 0.80, and 0.68. CONCLUSION: In this study, the authors created a dataset of 45 RLLS cases with multilevel annotations and developed a hybrid deep learning model for surgical workflow recognition. The authors demonstrated a fairly higher accuracy in multilevel effective surgical workflow recognition when under-effective frames were removed. Our research could be helpful in the development of autonomous robotic surgery.

The impact of COVID-19 on economy, air pollution and income: evidence from China.

The global pandemic caused by the outbreak of COVID-19 has posed significant risks to our health. Preventive measures such as closed management have greatly affected the economies, environments and societies of various countries. Economy, air pollution and income are three important interconnected aspects of sustainable development. However, current research lacks systematic quantitative analysis of their relationships. To fill the gap, this study adopts monthly data from January 2016 to April 2022 and constructs both a Simultaneous Equation Model (SEM) and a Time Varying Parameter Stochastic Volatility Vector Autoregressive (TVP-SV-VAR) model to empirically analyze the impact of COVID-19 on China's economy, air pollution and income. This study finds that the COVID-19 has a negative impact on China's economy and income, and a positive impact on air pollution, and the impact of the COVID-19 is systematic. In addition, there is an inverted-U shaped relationship between air pollution and economics, and a positive correlation between economic and income. The impact of COVID-19 on the economy, air pollution and income show a process of sharp fluctuations to gradual stabilization that gradually stabilized over time. This process is time-varying in the short-term, medium-term and long-term. The impacts are persistent at three different time points (before, during and after the outbreak of COVID-19), but the negative impact on the economy and income is persistent, while the positive impact on air pollution is limited. This study provides a more systematic and dynamic understanding of the COVID-19 preventive and mitigation measures in China and even the world, which helps to provide insights into the formulation of more comprehensive planning strategies in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s00477-023-02450-z.

G6PD activation in TNBC cells induces macrophage recruitment and M2 polarization to promote tumor progression.

Glucose-6-phosphate dehydrogenase (G6PD) is involved in triple-negative breast cancer (TNBC) progression. Metabolic crosstalk between cancer cells and tumor-associated macrophages mediates tumor progression in TNBC. Molecular biological methods were applied to clarify the mechanism of the crosstalk between TNBC cells and M2 macrophages. In the present study, we verified that G6PD overexpression drives M2 macrophage polarization by directly combining with phospho-STAT1 and upregulating CCL2 and TGF-ß1 secretion in TNBC cells. In turn, M2-like TAMs activated TNBC cells through IL-10 secretion, providing feedback to upregulate G6PD and promote TNBC cell migration and proliferation in vitro. Furthermore, we found that 6-AN (a specific inhibitor of G6PD) not only suppressed the cancer-driven polarization of macrophages toward the M2 phenotype but also inhibited the inherent M2 polarization of macrophages. Targeting the G6PD-regulated pentose phosphate pathway restrained TNBC progression and M2-type polarization of macrophages in vitro and in vivo.

Forward looking statement, investor sentiment and stock liquidity.

Information is a critical element of capital markets, and liquidity is the lifeblood of capital markets. Relative to historical information, forward-looking information is of significant value to investors. Based on textual analysis calculations, we selected Chinese A-share listed companies as a research sample to explore the impact of forward-looking information disclosure level on stock liquidity. It is found that the higher the level of forward-looking information disclosure, the better the stock liquidity. Investor sentiment is the transmission mechanism through which the forward looking statement disclosure level affects stock liquidity. The heterogeneity analysis shows that the level of forward-Looking statement disclosure has a more significant effect on stock liquidity improvement for state-owned enterprises and enterprises in low-market regions than those in regions with high marketization levels. The article expands and enriches the research on forward-looking information disclosure, and also has some reference value for regulators to formulate laws and regulations and regulate forward-looking information disclosure.

Comparison of survival benefit between salvage surgery after conversion therapy versus surgery alone for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

BACKGROUND: Salvage surgery after conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody has shown improved survival benefits in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We aimed to compare the survival benefits in a retrospective cohort of patients with HCC with PVTT who underwent salvage surgery after conversion therapy and surgery alone. METHODS: From January 2015 to October 2021, we selected patients diagnosed with HCC with PVTT who underwent liver resection at Chinese PLA General Hospital. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. RESULTS: The 6-, 12-, and 24-month recurrence-free survival rates in the conversion and surgery alone groups were 80.3% vs 36.5%, 65.4% vs 29.4%, and 56% vs 21%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. CONCLUSIONS: For patients with HCC with PVTT, surgery after conversion therapy is in relationship with increased survival in comparison with surgery alone.

Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of anatomical resection (AR) versus nonanatomical resection (NAR) combined with resection margin (RM) (narrow RM <1 cm vs. wide RM ≥1 cm) on long-term prognosis in hepatitis B virus-related HCC patients with MVI. MATERIALS AND METHODS: Data from multicenters on HCC patients with MVI who underwent hepatectomy was analyzed retrospectively. Propensity score matching analysis was performed in these patients. RESULTS: The 1965 enrolled patients were divided into four groups: AR with wide RM ( n =715), AR with narrow RM ( n =387), NAR with wide RM ( n =568), and NAR with narrow RM ( n =295). Narrow RM ( P <0.001) and NAR ( P <0.001) were independent risk factors for both overall survival and recurrence-free survival in these patients based on multivariate analyses. For patients in both the AR and NAR groups, wide RM resulted in significantly lower operative margin recurrence rates than those patients in the narrow RM groups after propensity score matching ( P =0.002 and 0.001). Patients in the AR with wide RM group had significantly the best median overall survival (78.9 vs. 51.5 vs. 48.0 vs. 36.7 months, P <0.001) and recurrence-free survival (23.6 vs. 14.8 vs. 17.8 vs. 9.0 months, P <0.001) than those in the AR with narrow RM, NAR with wide RM or with narrow RM groups, respectively. CONCLUSIONS: If technically feasible and safe, AR combined with wide RM should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI.