Correction: Hu et al. Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C. Biosensors 2023, 13, 645.

In the original publication [...].

Response of Seed Germination and Seedling Growth of Six Desert Shrubs to Different Moisture Levels under Greenhouse Conditions.

Moisture is the most important environmental factor limiting seed regeneration of shrubs in desert areas. Therefore, understanding the effects of moisture changes on seed germination, morphological and physiological traits of shrubs is essential for vegetation restoration in desert areas. In March to June 2023, in a greenhouse using the potting method, we tested the effects of soil moisture changes (5%, 10%, 15%, 20% and 25%) on seed germination and seedling growth of six desert shrubs (Zygophyllum xanthoxylum, Nitraria sibirica, Calligonum mongolicum, Corethrodendron scoparium, Caragana korshinskii, and Corethrodendron fruticosu). Results showed that (1) seed germination percent and vigor index were significantly higher at 15 and 20% soil moisture content than at 5 and 10%; (2) shoot length, primary root length, specific leaf area and biomass of seedlings were significantly higher in the 15% and 20% soil moisture content treatments than in the 5% and 10% treatments; (3) superoxide dismutase activity (SOD) and soluble protein content (SP) decreased with decreasing soil water content, while peroxidase activity (POD) and catalase activity (CAT) showed a decreasing and then increasing trend with increasing soil water content; (4) the six seeds and seedling of shrubs were ranked in order of their survivability in response to changes in soil moisture: Caragana korshinskii > Zygophyllum xanthoxylum > Calligonum mongolicum > Corethrodendron scoparium > Corethrodendron fruticosu > Nitraria sibirica. Our study shows that shrub seedlings respond to water changes by regulating morphological and physiological traits together. More importantly, we found that C. korshinskii, Z. xanthoxylum and C. mongolicum were more survivable when coping with water deficit or extreme precipitation. The results of the study may provide a reference for the selection and cultivation of similar shrubs in desert areas under frequent extreme droughts in the future.

Setup errors analysis in iterative kV CBCT: A clinical study of cervical cancer treated with Volumetric Modulated Arc Therapy.

OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.

A Study on the Dynamic Switching Characteristics of p-GaN HEMT Power Devices.

This study employs an innovative dynamic switching test system to investigate the dynamic switching characteristics of three p-GaN HEMT devices. The dynamic switching characteristics are different from the previous research on the dynamic resistance characteristics of GaN devices, and the stability of GaN devices can be analyzed from the perspective of switching characteristics. Based on the theory of dynamic changes in threshold opening voltage and capacitance caused by electrical stress, the mechanism of dynamic switching characteristics of GaN HEMT devices is studied and analyzed in detail. The test results have shown that electrical stress induces trap ionization within the device, resulting in fluctuations in electric potential and ultimately leading to alterations in two critical factors of the dynamic switching characteristics of GaN HEMT devices, the parasitic capacitance and the threshold voltage. The dynamic changes in capacitance before and after electrical stress vary among devices, resulting in different dynamic switching characteristics. The test system is capable of extracting the switching waveform for visual comparison and quantitatively calculating the changes in switching parameters before and after electrical stressing. This test provides a prediction for the drift of switch parameters, offering pre-guidance for the robustness of the optimized application scheme.

Seed traits and burial state affect plant seed secondary dispersal mediated by rodents.

Seed dispersal is an important ecological process and has important implications for plant population expansion and regeneration. Seed dispersal not only reduces the probability of death due to seed density but also facilitates seedling establishment. Many studies have focused on the effect of one or two factors on seed dispersal. However, little is known about studies on the effect of multiple factors and their interactions on seed dispersal. Here, we conducted a field experiment to explore how seed size, soil burial, and seed peeling affect the dispersal and hoarding of seeds of Quercus liaotungensis in dispersal animals. We found that large seeds were preferentially selected by animals, and the predation after dispersal, hoarding after dispersal, predation distance after dispersal, and hoarding distance after dispersal of large seeds were significantly greater than small seeds, which is more beneficial to the plant expansion and regeneration. Soil burial increased the time of seed intact in situ, significantly increased predation in situ, and reduced predation after dispersal, predation distance after dispersal, and hoarding distance after dispersal, which is not beneficial to the plant population expansion and regeneration. Seed peeling reduced the time of seed intact in situ, and the predation after dispersal was significantly greater than that of unpeeled seeds, which is not beneficial to the plant population. We did not find the interactions between seed size, soil burial, and seed peeling on dispersal. The effects of a single factor may be more than their interactions between seed size, soil burial and seed peeling on dispersal. These results implied that seed size, soil burial and seed peeling may affect plant population expansion and regeneration by affecting the dispersal and hoarding of animals.

A case report of hemophagocytic lymphohistiocytosis induced by toripalimab plus chemoradiotherapy in cervical cancer.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome characterized by immune hyperactivation. Unlike primary HLH, immune checkpoint inhibitor (ICI)-triggered HLH is not well described, and there is a lack of theranostic guidelines. Herein, we first reported the successful management of PD-1 inhibitor-associated HLH in locally advanced cervical cancer. Case presentation: We report a case of HLH in a 47-year-old patient with International Federation of Gynecology and Obstetrics (FIGO) IIIC1r cervical cancer who received toripalimab, a programmed cell death-1 receptor inhibitor, combined with chemoradiotherapy. The patient developed pyrexia, splenomegaly, leukopenia, anemia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, reduced NK cell activity, elevated sCD25 levels, and hemophagocytosis in a bone marrow aspirate. Our patient was successfully treated with methylprednisolone, indicating that immune-induced HLH might respond to glucocorticoids, and is still alive with a complete response of the tumor. Conclusion: Considering the possibility of HLH is needed in patients receiving ICIs to detect rare toxicities at an early stage when the patient develops uncontrollable fever, cytopenia, and splenomegaly, our multidisciplinary treatment modality contributed to the early diagnosis and successful management of HLH, avoiding progressive tissue damage and organ failure. Whether glucocorticoids are used alone or not for immune-associated HLH needs further investigation.

Stem Cell Division and Its Critical Role in Mammary Gland Development and Tumorigenesis: Current Progress and Remaining Challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetrical cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of BC stem cell division modes and cause BC. Important regulatory factors such as mammalian Inscuteable mInsc, Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

Transmission from seed to seedling and elimination of alfalfa viruses.

Introduction: Viral diseases have become a vital factor limiting the development of the alfalfa (Medicago sativa) industry. Six viruses infecting alfalfa with a high incidence rate are Alfalfa mosaic virus (AMV), Medicago sativa alphapartitivirus 1 (MsAPV1), Medicago sativa alphapartitivirus 2 (MsAPV2), Medicago sativa deltapartitivirus 1 (MsDPV1), Medicago sativa amalgavirus 1 (MsAV1), and Cnidium vein yellowing virus 1 (CnVYV1). The purpose of this study was to develop preventive measures against these viruses by investigating their transmission through alfalfa seeds. Methods: In this study, we investigated the transmission rate of alfalfa viruses from seed to seedling by PCR, determined the location of viruses in seed by dissecting seed embryos and seed coat, tracked the changes of viruses in seedlings, and finally discover effective elimination measures for alfalfa viruses from 16 measures. Results and discussion: Our results demonstrated that all these six viruses could be transmitted from alfalfa seeds to seedlings with the transmission rate ranging from 44.44% to 88.89%. For AMV, MsAPV2, and MsAV1, the viral load was significantly higher in the seed coats than in the seed embryos; however, it did not show significant differences between these two parts of the seeds for MsAPV1, MsDPV1, and CnVYV1. Dynamic accumulation analysis of AMV and MsAPV2 indicated that the viral load in plants increased continuously in the early growth stage, making it important to inactivate these viruses prior to their seed-to-seedling transmission. Sixteen treatments including physical, chemical, and combinations of physical and chemical measures were compared in terms of their elimination efficiency on AMV and MsAPV2 and impacts on seed germination. The results showed that soaking alfalfa seeds in sterile distilled water for 2h + 2% NaClO for 1h or 2% NaClO for 1h were more promisingly applicable because it could significantly reduce AMV and MsAPV2 particles in both seeds and seedlings. Our data revealed a route of virus transmission in alfalfa and shed light on the discovery of a highly efficient method for the management of alfalfa viral diseases.

Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

Construction of Fluorescent G-Quadruplex Nanowires for Label-Free and Accurate Monitoring of Circular RNAs in Breast Cancer Cells and Tissues with Low Background.

Circular RNAs (circRNAs) represent an emerging category of endogenous transcripts characterized by long half-life time, covalently closed structures, and cell-/tissue-specific expression patterns, making them potential disease biomarkers. Herein, we demonstrate the construction of fluorescent G-quadruplex nanowires for label-free and accurate monitoring of circular RNAs in breast cancer cells and tissues by integrating proximity ligation-rolling circle amplification cascade with lighting up G-quadruplex. The presence of target circRNA facilitates the SplintR ligase-mediated ligation of the padlock probe. Upon the addition of primers, the ligated padlock probe can serve as a template to initiate subsequent rolling circle amplification (RCA), generating numerous long G-quadruplex nanowires that can incorporate with thioflavin T (ThT) to generate a remarkably improved fluorescence signal. Benefiting from good specificity of SplintR ligase-mediated ligation reaction and exponential amplification efficiency of RCA, this strategy can sensitively detect target circRNA with a limit of detection of 4.65 × 10-18 M. Furthermore, this method can accurately measure cellular circRNA expression with single-cell sensitivity and discriminate the circRNA expression between healthy para-carcinoma tissues and breast cancer tissues, holding great potential in studying the pathological roles of circRNA and clinic diagnostics.

The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment.

Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis and has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes and both tumorigenesis and progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, and immunotherapy, the persistent hallmark of cancer enables malignant cells to elude cell death and develop resistance to therapy. Recent findings indicate that pyroptosis can overcome apoptosis resistance amplify treatment-induced tumor cell death. Moreover, pyroptosis triggers antitumor immunity by releasing pro-inflammatory cytokines, augmenting macrophage phagocytosis, and activating cytotoxic T cells and natural killer cells. Additionally, it transforms "cold" tumors into "hot" tumors, thereby enhancing the antitumor effects of various treatments. Consequently, pyroptosis is intricately linked to tumor development and holds promise as an effective strategy for boosting therapeutic efficacy. As the principal executive protein of pyroptosis, the gasdermin family plays a pivotal role in influencing pyroptosis-associated outcomes in tumors and can serve as a regulatory target. This review provides a comprehensive summary of the relationship between pyroptosis and gasdermin family members, discusses their roles in tumor progression and the tumor immune microenvironment, and analyses the underlying therapeutic strategies for tumor treatment based on pyroptotic cell death.

LmFKBP24 interacts with LmEaster to inhibit the antifungal immunity of Locusta migratoria.

Locusta migratoria is one of the most destructive pests that threaten crop growth and food production security in China. Metarhizium anisopliae has been widely used to control locusts around the world. Previous laboratory studies have revealed that LmFKBP24 is significantly upregulated after M. anisopliae infection, suggesting that it may play a role in immune regulation, yet the mechanism remains largely unknown. To gain further insight, we conducted an RNA interference (RNAi) study to investigate the function of LmFKBP24 in the regulation of antifungal immunity and analyzed the expression patterns of immune-induced genes. Our research revealed that LmFKBP24 is activated and upregulated when locusts are infected by M. anisopliae, and it inhibits the expression of antimicrobial peptide (AMP) defensin in the downstream of Toll pathway by combining with LmEaster rather than LmCyPA, thus exerting an immunosuppressive effect. To further investigate this, we conducted yeast two-hybrid (Y2H) and pull down assays to identify the proteins interacting with LmFKBP24. Our results provided compelling evidence for revealing the immune mechanism of L. migratoria and uncovered an innovative target for the development of new biological pesticides. Furthermore, our research indicates that LmFKBP24 interacts with LmEaster through its intact structure, providing a strong foundation for further exploration.

Novel Label-Free Nanocrystalline Gold Interdigitated Microelectrode Immunosensor for the Rapid and Ultrasensitive Detection of SARS-CoV-2.

Waves of COVID-19 outbreaks have dragged down the global economy and endangered human life. There is an urgent need for timeliness and sensitive SARS-CoV-2 detection techniques to complement the existing PCR assay. Herein, the controllable growth of gold crystalline grains was achieved by applying the reverse current during pulse electrochemical deposition (PED) interval. The proposed method validates the effects of pulse reverse current (PRC) on the atomic arrangement, crystal structures, orientations, and film characteristics in Au PED. The gap between the gold grains on the surface of the nanocrystalline gold interdigitated microelectrodes (NG-IDME) fabricated by the PED+PRC process matches the size of the antiviral antibody. Immunosensors are prepared by binding a large number of antiviral antibodies on the surface of NG-IDME. The NG-IDME immunosensor has a high specific capture ability for SARS-CoV-2 nucleocapsid protein (SARS-CoV-2/N-Pro) and completes ultrasensitive and quantification of SARS-CoV-2/N-Pro in humans and pets within 5 min (the LOQ as low as 75 fg/mL). The specificity, accuracy, stability, and actual blind sample tests show that the NG-IDME immunosensor is suitable for the detection of SARS-CoV-2 in humans and animals. This approach assists in monitoring the transmission of SARS-CoV-2-infected animals to humans.

Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C.

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Gasdermin D Plays an Oncogenic Role in Glioma and Correlates to an Immunosuppressive Microenvironment.

BACKGROUND: Understanding the molecular mechanisms driving oncogenic processes in glioma is important in order to develop efficient treatments. Recent studies have proposed gasdermin D (GSDMD) as a newly discovered pyroptosis executive protein associated with tumorigenesis. However, the precise effect of GSDMD on glioma progression remains unknown. METHODS: The expression levels of GSDMD in 931 glioma and 1157 normal control tissues were collected. A series of bioinformatic approaches and in vivo and in vitro experiments were used to investigate the roles and mechanisms of GDSMD in glioma. RESULTS: Significant upregulation of GSDMD was detected in glioma tissues compared to normal brain tissues. Patients with glioma and higher GSDMD levels had shorter overall survival, and the Cox regression analysis revealed that GSDMD was an independent risk factor. In addition, upregulation of GSDMD was associated with higher tumor mutation burden and PD-1/PD-L1 expression. Immune infiltration and single-cell analyses indicated that GSDMD was positively associated with an immunosuppressive microenvironment with more infiltrated macrophages and cancer-associated fibroblasts. Furthermore, the in vitro and in vivo experiments revealed that GSDMD knockdown inhibited glioma proliferation, migration, and growth in vivo. CONCLUSION: Our analyses revealed a relatively comprehensive understanding of the oncogenic role of GSDMD in glioma. GSDMD is a promising prognostic biomarker and a potential target for glioma treatment.

The Efficacy of Volumetric Modulated Arc Therapy Combined With Chemotherapy, Brachytherapy, and Local Hyperthermia on Patients with Locally Advanced Cervical Cancer: A Retrospective Study.

OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.

Harnessing NK cell-based immunotherapy to prevent the high-dose radiotherapy-inducing tumor survival recurrence.

Natural killer cells play crucial roles in tumor immunosurveillance and serve as first responders to recognize abnormal cells. Radiotherapy is the mainstay of cancer treatment. However, the effect of high-dose radiotherapy on NK cells remains elusive. Here, we used tumor-bearing mice in the murine colorectal cancer cell line, MC38. The function of NK cells in tumor-draining lymph nodes and tumors was explored after the mice were treated using radiotherapy with 20 Gy and/or blocking antibody αTIGIT at the indicated time. High-dose radiotherapy shaped an immunosuppressive tumor microenvironment to support tumor growth, showing a decreased anti-tumor immunity phenotype in which effector T cells were reduced significantly. Furthermore, the production of functional cytokines and markers in NK cells, including CD107a, granzyme B, and IFN-γ, also remarkably decreased after radiotherapy, while the inhibitory receptor TIGIT was significantly upregulated by FACS analysis. The effect of radiotherapy was significantly elevated after treatment with the combination of radiotherapy and TIGIT inhibition. Moreover, this combination significantly decreased tumor recurrence. Our findings reported that local single high-dose radiotherapy shaped the immunosuppressive microenvironment and inhibited the function of NK cells. Our study revealed compelling evidence suggesting that the enhancement of NK cell function through TIGIT targeting is an effective strategy to mitigate immune suppression caused by high-dose radiotherapy, thereby promoting the inhibition of tumor recurrence.

Target immune components to circumvent sorafenib resistance in hepatocellular carcinoma.

Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment for decades, especially hepatocellular carcinoma (HCC). Although sorafenib produced substantial clinical benefits in the initial stage, a large proportion of cancer patients acquired drug resistance in subsequent treatment, which always disturbs clinical physicians. Cumulative evidence unraveled the underlying mechanism of sorafenib, but few reports focused on the role of immune subpopulations, since the immunological rationale of sorafenib resistance has not yet been defined. Here, we reviewed the immunoregulatory effects of sorafenib on the tumor microenvironment and emphasized the potential immunological mechanisms of therapeutic resistance to sorafenib. Moreover, we also summarized the clinical outcomes and ongoing trials in combination of sorafenib with immunotherapy, highlighted the immunotherapeutic strategies to improve sorafenib efficacy, and put forward several prospective questions aimed at guiding future research in overcoming sorafenib resistance in HCC.

The role of macrophages-mediated communications among cell compositions of tumor microenvironment in cancer progression.

Recent studies have revealed that tumor-associated macrophages are the most abundant stromal cells in the tumor microenvironment and play an important role in tumor initiation and progression. Furthermore, the proportion of macrophages in the tumor microenvironment is associated with the prognosis of patients with cancer. Tumor-associated macrophages can polarize into anti-tumorigenic phenotype (M1) and pro-tumorigenic phenotype (M2) by the stimulation of T-helper 1 and T-helper 2 cells respectively, and then exert opposite effects on tumor progression. Besides, there also is wide communication between tumor-associated macrophages and other immune compositions, such as cytotoxic T cells, regulatory T cells, cancer-associated fibroblasts, neutrophils and so on. Furthermore, the crosstalk between tumor-associated macrophages and other immune cells greatly influences tumor development and treatment outcomes. Notably, many functional molecules and signaling pathways have been found to participate in the interactions between tumor-associated macrophages and other immune cells and can be targeted to regulate tumor progression. Therefore, regulating these interactions and CAR-M therapy are considered to be novel immunotherapeutic pathways for the treatment of malignant tumors. In this review, we summarized the interactions between tumor-associated macrophages and other immune compositions in the tumor microenvironment and the underlying molecular mechanisms and analyzed the possibility to block or eradicate cancer by regulating tumor-associated macrophage-related tumor immune microenvironment.

The value of CT radiomics features to predict visceral pleural invasion in ≤3 cm peripheral type early non-small cell lung cancer.

OBJECTIVE: To investigate predictive value of CT-based radiomics features on visceral pleural invasion (VPI) in ≤3.0 cm peripheral type early non-small cell lung cancer (NSCLC). METHODS: A total of 221 NSCLC cases were collected. Among them, 115 are VPI-positive and 106 are VPI-negative. Using a stratified random sampling method, 70% cases were assigned to training dataset (n = 155) and 30% cases (n = 66) were assigned to validation dataset. First, CT findings, imaging features, clinical data and pathological findings were retrospectively analyzed, the size, location and density characteristics of nodules and lymph node status, the relationship between lesions and pleura (RAP) were assessed, and their mean CT value and the shortest distance between lesions and pleura (DLP) were measured. Next, the minimum redundancy-maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) features were extracted from the imaging features. Then, CT imaging prediction model, texture feature prediction model and joint prediction model were built using multifactorial logistic regression analysis method, and the area under the ROC curve (AUC) was applied to evaluate model performance in predicting VPI. RESULTS: Mean diameter, density, fractal relationship with pleura, and presence of lymph node metastasis were all independent predictors of VPI. When applying to the validation dataset, the CT imaging model, texture feature model, and joint prediction model yielded AUC = 0.882, 0.824 and 0.894, respectively, indicating that AUC of the joint prediction model was the highest (p < 0.05). CONCLUSION: The study demonstrates that the joint prediction model containing CT morphological features and texture features enables to predict the presence of VPI in early NSCLC preoperatively at the highest level.