Diagnostic value of contrast-enhanced CT in clear cell renal cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Contrast-enhanced computed tomography (CECT) improves lesion contrast with surrounding tissues through the injection of contrast agents. This enhancement allows for more precise lesion characterization, aiding in the early diagnosis of clear cell renal cell carcinoma (ccRCC). This meta-analysis aims to assess the diagnostic efficacy of CECT in ccRCC and to provide an ideal imaging examination method for the preoperative diagnosis of ccRCC. METHODS: We conducted a comprehensive search across six major online databases: PubMed, Web of Science, Cochrane Library, WANFANG DATA, China National Knowledge Infrastructure, and Chinese BioMedical Literature Database (CBM). The objective was to collate and analyze studies that evaluate the diagnostic utility of CECT in the identification of ccRCC. Meta-disc 1.4 and Stata 16.0 were used to conduct a meta-analysis and evaluate the diagnostic accuracy of CECT for ccRCC. RESULTS: The meta-analysis included 17 relevant studies investigating the diagnostic value of CECT for ccRCC. The combined sensitivity and specificity of CECT were 0.88 (95% confidence interval: 0.83-0.91) and 0.82 (95%CI: 0.75-0.87), respectively. Positive diagnostic likelihood ratio = 4.87 (95%CI: 3.47-6.84), negative diagnostic likelihood ratio = 0.15 (95%CI: 0.11-0.21), and diagnostic odds ratio = 32.67 (95%CI: 18.21-58.61). In addition, the area under the ROC curve was 0.92 (95%CI: 0.89-0.94), indicating that CECT has a decent discriminative ability in diagnosing ccRCC. CONCLUSIONS: CECT is recognized as a highly effective imaging tool for diagnosing ccRCC. It provides valuable guidance in the preoperative assessment and planning of surgical strategies for patients with ccRCC.

Electrical Impedance Tomography Identifies Evolution of Regional Perfusion in a Porcine Model of Acute Respiratory Distress Syndrome.

BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.

TRIM58 functions as a tumor suppressor in colorectal cancer by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway.

BACKGROUND: This study aimed to investigate the underlying molecular mechanisms of TRIM58 in the development of colorectal cancer (CRC). CRC is one of the most common cancers of the digestive tract worldwide. The ubiquitin-proteasome system regulates many oncogenic or tumor-suppressive proteins. TRIM58, an E3 ubiquitin ligase and a member of the tripartite motif protein family, is a potential prognostic marker that indicates poor prognosis in cancer. Currently, the precise molecular mechanisms for the TRIM58-mediated CRC progression remain unclear. METHODS: To examine the effects of TRIM58 on cell viability, cell cycle progression, and apoptosis in CRC, Cell Counting Kit-8 and flow cytometry assays were employed. The AKT inhibitor LY294002 was used to examine the effects of AKT signaling on TRIM58-mediated cell viability, cell cycle progression, and apoptosis in CRC. Additionally, Co-IP and ubiquitination assays were used to examine the correlation between TRIM58 and RECQL4. RESULTS: TRIM58 overexpression inhibited CRC cell viability and promoted cell cycle arrest and apoptosis, in which the TRIM58 knockdown demonstrated inversed effects via the AKT signaling pathway. TRIM58 inhibited RECQL4 protein levels through its ubiquitin ligase activity, and RECQL4 overexpression inhibited TRIM58 overexpression-mediated CRC cell viability, cell cycle progression, and apoptosis. The downregulation of TRIM58 and upregulation of RECOL4 were observed in human CRC tissue, and TRIM58 demonstrated antitumor effects in CRC-induced tumor growth in a mouse model. CONCLUSIONS: TRIM58 acts as a tumor suppressor in CRC through the promotion of RECQL4 ubiquitination and inhibition of the AKT signaling pathway and may be investigated for the successful treatment of CRC.

Anaerobic co-digestion of poultry litter and wheat straw affected by solids composition, free ammonia and carbon/nitrogen ratio.

In this study, the effects of three total solids levels (2%, 5% and 10% TS) of the mixtures of poultry litter and wheat straw at different percent volatile solids from wheat straw (0%, 25% and 50% VSWS), free ammonia nitrogen (FAN) and C/N ratio on co-digesting poultry litter with wheat straw were studied in batch experiments operated at 37 °C. The results showed that adjusting the substrate C/N ratio alone could not always result in high methane yields and biogas volumes. The maximum CH4 yield of 201 mL g-1 initial VS was observed in the 5% TS category with VSWS being 50%. The highest specific biogas volume produced (318 mL g-1 initial VS) was also obtained in the same solid category. A polynomial regression between FAN and the methanogenic activity was obtained with the correlation coefficient being 0.9472. A FAN inhibitory threshold concentration of 253.9 mg L-1 was found, and a total loss of methane production occurred when the FAN concentration reached 1000 mg L-1. An optimal TS content for anaerobic digestion of poultry litter with wheat straw was around 4.15% to achieve the best biogas yield. Similarly, for digesting poultry litter without addition of wheat straw, the TS content should be kept at around 6.8%.

Kinetics of batch anaerobic co-digestion of poultry litter and wheat straw including a novel strategy of estimation of endogenous decay and yield coefficients using numerical integration.

The kinetics of anaerobic co-digestion of poultry litter and wheat straw has not been widely reported in the literature. Since endogenous decay and yield coefficients are two basic parameters for the design of anaerobic digesters, they are currently estimated only by continues experiments. In this study, numerical integration was employed to develop a novel strategy to estimate endogenous decay and yield coefficients using initial and final liquid data combined with methane volumes produced over time in batch experiments. To verify this method, the kinetics of batch anaerobic co-digestion of poultry litter and wheat straw at different TS and VS levels was investigated, with the corresponding endogenous decay and (non-observed) yield coefficients in the exponential periods determined to be between 0.74 × 10(-3) and 6.1 × 10(-3) d(-1), and between 0.0259 and 0.108 g VSS (g VS)(-1), respectively. A general Gompertz model developed early for bio-product could be used to simulate the methane volume profile in the co-digestion. The same model parameters obtained from the methane model combined with the corresponding yield coefficients could also be used to describe the VSS generation and VS destruction.

Optimization of methane production in anaerobic co-digestion of poultry litter and wheat straw at different percentages of total solid and volatile solid using a developed response surface model.

Poultry litter (PL) can be good feedstock for biogas production using anaerobic digestion. In this study, methane production from batch co-digestion of PL and wheat straw (WS) was investigated for two factors, i.e., total solid (2%, 5%, and 10%) and volatile solid (0, 25, and 50% of WS), constituting a 3 × 3 experimental design. The results showed that the maximum specific methane volume [197 mL (g VS)(­1)] was achieved at 50% VS from WS at 5% TS level. It was estimated that the inhibitory threshold of free ammonia was about 289 mg L(--1), beyond which reduction of methanogenic activity by at least 54% was observed. The specific methane volume and COD removal can be expressed using two response surface models (R(2) = 0.9570 and 0.9704, respectively). Analysis of variance of the experimental results indicated that the C/N ratio was the most significant factor influencing the specific methane volume and COD removal in the co-digestion of these two materials.

Evaluation of perceived urgency from single-trial EEG data elicited by upper-body vibration feedback using deep learning.

Notification systems that convey urgency without adding cognitive burden are crucial in human-computer interaction. Haptic feedback systems, particularly those utilizing vibration feedback, have emerged as a compelling solution, capable of providing desirable levels of urgency depending on the application. High-risk applications require an evaluation of the urgency level elicited during critical notifications. Traditional evaluations of perceived urgency rely on subjective self-reporting and performance metrics, which, while useful, are not real-time and can be distracting from the task at hand. In contrast, EEG technology offers a direct, non-intrusive method of assessing the user's cognitive state. Leveraging deep learning, this study introduces a novel approach to evaluate perceived urgency from single-trial EEG data, induced by vibration stimuli on the upper body, utilizing our newly collected urgency-via-vibration dataset. The proposed model combines a 2D convolutional neural network with a temporal convolutional network to capture spatial and temporal EEG features, outperforming several established EEG models. The proposed model achieves an average classification accuracy of 83% through leave-one-subject-out cross-validation across three urgency classes (not urgent, urgent, and very urgent) from a single trial of EEG data. Furthermore, explainability analysis showed that the prefrontal brain region, followed by the central brain region, are the most influential in predicting the urgency level. A follow-up neural statistical analysis revealed an increase in event-related synchronization (ERS) in the theta frequency band (4-7 Hz) with the increased level of urgency, which is associated with high arousal and attention in the neuroscience literature. A limitation of this study is that the proposed model's performance was tested only the urgency-via-vibration dataset, which may affect the generalizability of the findings.

Immunoreactive Microenvironment Modulator GBP5 Suppresses Ovarian Cancer Progression by Inducing Canonical Pyroptosis.

Ovarian cancer has the highest mortality among gynecological malignancies, and exploring effective strategies to reverse the immunosuppressive tumor microenvironment in patients remains a pressing scientific challenge. In this study, we identified a pyroptosis-related protective factor, GBP5, which significantly inhibits the growth of ovarian cancer cells and patient-derived ovarian cancer organoids, impeding the invasion and migration of ovarian cancer cells. Results of immunohistochemistry and external single-cell data verification were consistent. Further research confirmed that GBP5 in ovarian cancer cell can induce canonical pyroptosis through JAK2/STAT1 pathway, thereby restraining the progression of ovarian cancer. Interestingly, in this study, we also discovered that ovarian cancer cells with high GBP5 expression exhibit increased expressions of CXCL9/10/11 in a co-culture assay. Subsequent immune cell infiltration analyses revealed the remodeling of immunosuppressive microenvironment in ovarian cancer patients, characterized by increased infiltration and polarization of M1 macrophages. External immunotherapy database analysis showed profound potential for the application of GBP5 in immunotherapy strategies for ovarian cancer. Overall, our study demonstrates that the protective factor GBP5 significantly inhibits ovarian cancer progression, triggering canonical pyroptosis through the JAK2-STAT1 pathway. Driven by its pro-inflammatory nature, it can also enhance M1 macrophages polarization and reverse immunosuppressive microenvironment, thus providing new insights for ovarian cancer treatment.

The Impact of Different Smoking Behavior on Pulmonary Function and Pulmonary Hypertension Among Chinese Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD. Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH. Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP. Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.

A dataset for fine-grained seed recognition.

The research of plant seeds has always been a focus of agricultural and forestry research, and seed identification is an indispensable part of it. With the continuous application of artificial intelligence technology in the field of agriculture, seed identification through computer vision can effectively promote the development of agricultural and forestry wisdom. Data is the foundation of computer vision, but there is a lack of suitable datasets in the agricultural field. In this paper, a seed dataset named LZUPSD is established. A device based on mobile phones and macro lenses was established to acquire images. The dataset contains 4496 images of 88 different seeds. This dataset can not only be used as data for training deep learning models in the computer field, but also provide important data support for agricultural and forestry research. As an important resource in this field, this dataset plays a positive role in modernizing agriculture and forestry.

Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4.

Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.

Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice.

BACKGROUND: Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS: 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS: We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION: Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.

Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy.

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.

OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION: Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

Application of a reaction model to improve calculation of the sugar recovery standard for sugar analysis.

A kinetic model was applied to improve determination of the sugar recovery standard (SRS) for biomass analysis. Three sets of xylose (0.10-1.00 g/L and 0.999-19.995 g/L) and glucose (0.206-1.602 g/L) concentrations were measured by HPLC following reaction of each for 1 h. Then, parameters in a kinetic model were fit to the resulting sugar concentration data, and the model was applied to predict the initial sugar concentrations and the best SRS value (SRS(p)). The initial sugar concentrations predicted by the model agreed with the actual initial sugar concentrations. Although the SRS(e) calculated directly from experimental data oscillated considerably with sugar concentration, the SRS(p) trend was smooth. Statistical analysis of errors and application of the F-test confirmed that application of the model reduced experimental errors in SRS(e). Reference SRS(e) values are reported for the three series of concentrations.

Identification of a Ferroptosis-Related Prognostic Gene PTGS2 Based on Risk Modeling and Immune Microenvironment of Early-Stage Cervical Cancer.

Background: Cervical cancer (CC) has long been a concern, as a gynecological cancer type of high-risk. At present, there are few studies on the early detection of CC at the genetic level. The breakthrough is to recognize CC patients tending to have a worse prognosis by checking the expression pattern of ferroptosis-related genes, which enjoy a great potential of being applied to cancer treatment. Methods: Data used in this study was obtained from a series of public online databases, integrated with ferroptosis-related gene collection stored from the FerrDb database and GeneCards database. The least absolute shrinkage and selection operator- (LASSO-) penalized analysis was taken for modeling, and before, univariate Cox regression analysis got done to shrink the candidates' range. Several analyses were made for the evaluation of the efficacy of the new model, based on CC patients' overall survival (OS). Tumor microenvironment- (TME-) related analyses were conducted by various algorithms on different populations, comprising CIBERSORT, ssGSEA, XCELL, etc. Nonnegative matrix factorization (NMF) clustering got applied to find that ferroptosis-marker genes affect prognosis more than "driver" and "suppressor". Hub-gene PTGS2 was screened out by protein-protein interaction analysis and real-time qPCR after ferroptosis induction, and ELISA was conducted for further verification on the correlation between ferroptosis and M1 polarization. Results: The twenty-five ferroptosis-related genes model can estimate the prognosis of patients independently of other clinical factors, and the low-risk score group shows higher expression of immune-enhancing cells, noteworthily for M1 macrophages. It is experimentally validated that the M1 marker TNF-α significantly increased after coculturing M1 macrophages and SiHa cells processed with ferroptosis inductor before. The key gene to the model, PTGS2, presented to be a risk factor in cervical cancer, and its low-expression group has stronger immune activity and higher tumor mutation burden, with the significantly highly mutated gene TENM2 in it showing high drug sensitivity and neoantigen for patients with its mutant-type. Meanwhile, it influences macrophage polarization. Conclusion: Prognosis of early-stage cervical cancer patients can be exactly predicted on ferroptosis-related genes. Among model genes, PTGS2 may have a major impact by affecting macrophage polarization and mutation effects.

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis.

Ovarian cancer (OC) is the most lethal gynecological malignancy, in which chemoresistance is a crucial factor leading to the poor prognosis. Recently, immunotherapy has brought new light for the treatment of solid tumors. Hence, as a kind of immunologically active cancer, it is reasonably necessary to explore the potential mechanism between immune characteristics and cisplatin resistance in OC. Our study focused on the important role of cisplatin resistance-related lncRNAs on mediating the OC tumor immune microenvironment (TIME) using an integrative analysis based on the Cancer Genome Atlas (TCGA) database. First, the cisplatin resistance-related differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were preliminarily screened to construct a DEL-DEM co-expression network. Next, the protein-protein interaction (PPI) network and pivot analysis were performed to reveal the relevance of these lncRNAs with tumor immune response. Second, the novel lncRNA CTD-2288O8.1 was identified as a key gene for the OC cisplatin resistance formation by qRT-PCR and survival analysis. Gain- and loss-of-function assays (Cell Counting Kit-8 (CCK-8) assay, wound-healing scratch assay, transwell assay, and colony formation assay) further verified the activity of CTD-2288O8.1 in OC progression as well. Third, gene set enrichment analysis (GSEA) was applied along with the correlation analyses of CTD-2288O8.1 with ImmuneScore, tumor-infiltrating immune cells (TICs), and immune inhibitory checkpoint molecules, illustrating that CTD-2288O8.1 was strongly associated with the TIME and has the potential to predict the effect of OC immunotherapy. In addition, basic experiments demonstrated that the expression of CTD-2288O8.1 impacted the EGFR/AKT signal pathway activity of OC tumor cells. Of greater significance, it promoted the M2 polarization of macrophage, which is a type of the most important components of the TIME in solid tumor. Taking together, our study revealed cisplatin resistance-related lncRNAs closely linked with tumor immunity in OC, underscoring the potential mechanism of the TIME in conferring cisplatin resistance, which provided the research basis for further clinical treatment. CTD-2288O8.1 was identified to mediate cisplatin resistance and affect the response of immunotherapy, which could serve as a promising biomarker for guiding clinical treatment and improving prognosis in OC.

Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer.

Cervical cancer (CC) is a malignancy that tends to have a poor prognosis when detected at an advanced stage; however, there are few studies on the early detection of CC at the genetic level. The tumor microenvironment (TME) and genomic instability (GI) greatly affect the survival of tumor patients via effects on carcinogenesis, tumor growth, and resistance. It is necessary to identify biomarkers simultaneously correlated with components of the TME and with GI, as these could predict the survival of patients and the efficacy of immunotherapy. In this study, we extracted somatic mutational data and transcriptome information of CC cases from The Cancer Genome Atlas, and the GSE44001 dataset from the Gene Expression Omnibus database was downloaded for external verification. Stromal components differed most between genomic unstable and genomic stable groups. Differentially expressed genes were screened out on the basis of GI and StromalScore, using somatic mutation information and ESTIMATE methods. We obtained the intersection of GI- and StromalScore-related genes and used them to establish a four-gene signature comprising RIPOR2, CCL22, PAMR1, and FBN1 for prognostic prediction. We described immunogenomic characteristics using this risk model, with methods including CIBERSORT, gene set enrichment analysis (GSEA), and single-sample GSEA. We further explored the protective factor RIPOR2, which has a close relationship with ImmuneScore. A series of in vitro experiments, including immunohistochemistry, immunofluorescence, quantitative reverse transcription PCR, transwell assay, CCK8 assay, EdU assay, cell cycle detection, colony formation assay, and Western blotting were performed to validate RIPOR2 as an anti-tumor signature. Combined with integrative bioinformatic analyses, these experiments showed a strong relationship between RIPOR2 with tumor mutation burden, expression of genes related to DNA damage response (especially PARP1), TME-related scores, activation of immune checkpoint activation, and efficacy of immunotherapy. To summarize, RIPOR2 was successfully identified through comprehensive analyses of the TME and GI as a potential biomarker for forecasting the prognosis and immunotherapy response, which could guide clinical strategies for the treatment of CC patients.

NMR-based metabonomics reveals the dynamic effect of electro-acupuncture on central nervous system in gastric mucosal lesions (GML) rats.

BACKGROUND: Gastric mucosal lesions (GML) are common in gastric diseases and seriously affect the quality of life. There are inevitable side effects in drug therapy. Acupuncture is an important part of traditional Chinese medicine. Electro-acupuncture (EA) has unique curative effect in treatment of GML. However, there are still few reports on the central mechanism of electro-acupuncture in treatment of GML. In this study, NMR metabonomics was used to explore the central metabolic change mechanism of electro-acupuncture in treatment of GML. METHODS: SD rats were randomly divided into Control, GML and EA groups. According to different intervention time, each group was further divided into 3 subgroups. This study mainly established GML model rats by 75% ethanol. Dynamic expressions of metabolites in cerebral cortex and medulla were observed by 1D 1H Nuclear Magnetic Resonance (NMR) metabolomics, combined with gastric mucosal histopathological examination to evaluate the time-effect relationship of electro-acupuncture at Zusanli (ST36) and Liangmen (ST21) points for 1 day, 4 days and 7 days treatment of GML. RESULTS: The results showed that the repair effect of electro-acupuncture on gastric mucosal injury was the most obvious in 4 days and stable in 7 days, and 4 days electro-acupuncture can effectively inhibit GML gastric mucosal inflammation and the expression of inflammatory cells. Meanwhile, the NMR spectrum results of medulla and cerebral cortex showed that, 21 potential metabolites were identified to participate in the mechanism of pathogenesis of GML and the regulation of electro-acupuncture, including 15 in medulla and 10 in cerebral cortex. Metabolic pathway analysis showed that the differential metabolites involved 19 metabolic pathways, which could be divided into energy, neurotransmitters, cells and cell membrane and antioxidation according to their functions. The correlation analysis of stomach, medulla and cerebral cortex shows that the stimulation signal of GML may reach the cerebral cortex from the stomach through medulla, and electro-acupuncture can treat GML by regulating the central nervous system (CNS). CONCLUSIONS: 4 days electro-acupuncture treatment can significantly improve gastric mucosal injury, and the curative effect tends to be stable in 7 days treatment. Meanwhile, the pathogenesis of GML and the efficacy of electro-acupuncture involve metabolic pathways such as energy, neurotransmitters, cells and antioxidation, and electro-acupuncture can treat GML by regulating CNS.

MicroRNA-34a: A Novel Therapeutic Target in Fibrosis.

Fibrosis can occur in many organs, and severe cases leading to organ failure and death. No specific treatment for fibrosis so far. In recent years, microRNA-34a (miR-34a) has been found to play a role in fibrotic diseases. MiR-34a is involved in the apoptosis, autophagy and cellular senescence, also regulates TGF-ß1/Smad signal pathway, and negatively regulates the expression of multiple target genes to affect the deposition of extracellular matrix and regulate the process of fibrosis. Some studies have explored the efficacy of miR-34a-targeted therapies for fibrotic diseases. Therefore, miR-34a has specific potential for the treatment of fibrosis. This article reviews the important roles of miR-34a in fibrosis and provides the possibility for miR-34a as a novel therapeutic target in fibrosis.