Improving Fine Particle Removal Using a Single-Channel Slit Bubbling Device in Wet Flue Gas Desulfurization System.

To improve the cleanliness of coal-fired power plants' particulate matter emissions, a novel device (single-channel slit bubbling particle removal device (SCSB-PRD)) is proposed to improve the wet flue gas desulfurization system's (WFGDs) collaborative particle removal effect. Actual coal-fired flue gas was used to test the particle removal performance. The results showed that the flue gas temperature had no obvious effect on the scrubbing effect of the SCSB-PRD. The scrubbing space, scrubbing liquid volume, and flue gas flow rate effectively changed the gas-liquid flow state, and the bubbling state was the key factor in particle removal. The jet-bubbling contact state was more conducive to removing particles than the foam bubbling state. The jet-bubbling state improved the removal efficiency of fine particles by approximately 30% compared to the foam bubbling state. The device operated in a single stage, and the removal performance of the particulate matter reached more than 60%. Even the submicron particles had a satisfactory removal performance of greater than 50%. The particulate matter concentration at the outlet of the WFGDs was reduced to less than 10 mg/m3, which provides a feasible transformation path for ultraultra-low emissions of particulate matter from coal-fired power plants.

Effect of dexmedetomidine infusion on postoperative sleep disturbances in women with breast cancer: A monocentric randomized-controlled double-blind trial.

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).

Copper in Cancer: from transition metal to potential target.

In recent years, with the continuous in-depth exploration of the molecular mechanisms of tumorigenesis, numerous potential new targets for cancer treatment have been identified, some of which have been further developed in clinical practice and have produced positive outcomes. Notably, researchers' initial motivation for studying copper metabolism in cancer stems from the fact that copper is a necessary trace element for organisms and is closely connected to body growth and metabolism. Moreover, over the past few decades, considerable progress has been made in understanding the molecular processes and correlations between copper and cancer. Certain achievements have been made in the development and use of relevant clinical medications. The concept of "cuproptosis," a novel concept that differs from previous forms of cell death, was first proposed by a group of scientists last year, offering fresh perspectives on the targeting capabilities of copper in the treatment of cancer. In this review, we introduced the fundamental physiological functions of copper, the key components of copper metabolism, and a summary of the current research contributions on the connection between copper and cancer. In addition, the development of new copper-based nanomaterials and their associated mechanisms of action are discussed. Finally, we described how the susceptibility of cancer cells to this metallic nutrition could be leveraged to further improve the existing cancer treatment paradigm in the new setting.

Tunable Optical Frequency Comb Generated Using Periodic Windows in a Laser and Its Application for Distance Measurement.

A novel method for the generation of an optical frequency comb (OFC) is presented. The proposed approach uses a laser diode with optical feedback and operating at a specific nonlinear dynamic state named periodic window. In this case, the laser spectrum exhibits a feature with a series of discrete, equally spaced frequency components, and the repetition rate can be flexibly adjusted by varying the system parameters (e.g., external cavity length), which can provide many potential applications. As an application example, a dual-OFC system for distance measurement is presented. The results demonstrate the system's ability to achieve target distance detection, underscoring its potential for real-world applications in this field.

Ionic liquids with reversible photo-induced conductivity regulation in aqueous solution.

Stimulus-responsive ionic liquids have gained significant attention for their applications in various areas. Herein, three kinds of azobenzimidazole ionic liquids with reversible photo-induced conductivity regulation were designed and synthesized. The change of electrical conductivity under UV/visible light irradiation in aqueous solution was studied, and the effect of chemical structure and concentration of ionic liquids containing azobenzene to the regulation of photoresponse conductivity were discussed. The results showed that exposing the ionic liquid aqueous solution to ultraviolet light significantly increased its conductivity. Ionic liquids with longer alkyl chains exhibited an even greater increase in conductivity, up to 75.5%. Then under the irradiation of visible light, the electrical conductivity of the solution returned to its initial value. Further exploration of the mechanism of the reversible photo-induced conductivity regulation of azobenzene ionic liquids aqueous solution indicated that this may attributed to the formation/dissociation of ionic liquids aggregates in aqueous solution induced by the isomerization of azobenzene under UV/visible light irradiation and resulted the reversible conductivity regulation. This work provides a way for the molecular designing and performance regulation of photo-responsive ionic liquid and were expected to be applied in devices with photoconductive switching and micro photocontrol properties.

Pseudotargeted metabolomics-based random forest model for tracking plant species from herbal products.

BACKGROUND: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions. PURPOSE: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products. METHODS: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products. RESULTS: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products. CONCLUSION: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.

Resveratrol induces the growth inhibition of CDX-deficient gastric cancer cells using CDX2 and RUNX3 via the ß-catenin/TCF4 signaling pathway.

This study aimed to determine the expression levels of runt-related transcription factor 3 (RUNX3) and caudal-related homeobox 2 (CDX2) in patients with chronic gastritis, intestinal metaplasia, atypical hyperplasia, and gastric cancer (GC). To analyze the overexpression of CDX2 and the effects of resveratrol (Res) on MKN7 and TMK1 cells, immunohistochemical staining was performed to determine the protein expression levels in tissue samples. The biological activity of MKN7 and TMK1 cells was determined. Relative mRNA and protein expression levels were also determined. RUNX3 expression was positively correlated with CDX2 expression and negatively correlated with ß-catenin and transcription factor 4 (TCF-4) levels in GC tissues. Interestingly, RUNX3 expression was negatively correlated with CDX2 expression in other tissues. CDX2 overexpression or Res treatment inhibited cell proliferation, migration, and invasion, while inducing cell apoptosis. Furthermore, RUNX3 and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) expression levels were increased, while those of of ß-catenin, TCF-4, and Bcl-2 were decreased in the CDX2 group. Upon treatment with lithium chloride (LiCl), the proliferation, migration, and invasion of CDX2-overexpressing MKN7 and TMK1 cells were enhanced. Our results indicate that Res inhibits the growth of MKN7 and TMK1 cells by increasing RUNX3 and CDX2 expression levels, with the potential involvement of the ß-catenin/TCF-4 signaling pathway.

Colorectal cancer with testicular metastasis: A case report and literature review.

RATIONALE: Colorectal cancer is the second leading cause of cancer-related deaths in the world. About 50% of patients will have metastases during the course of the disease. The common sites of metastasis are the liver, lung, peritoneum, lymph, etc. Metastatic carcinoma to the testes is uncommon. We found a case of ascending colon cancer metastasized to the testis in the clinic. PATIENT CONCERNS: We reported a 50-year-old male patient who was found to have testicular metastases >4 years after intestinal cancer surgery, and multiple metastases in the peritoneum and pelvis were found 1 week later. DIAGNOSES: After enhanced computed tomography and pathological biopsy, the patient was diagnosed with testicular metastasis of colon cancer. INTERVENTIONS: Capecitabine combined with bevacizumab is currently undergoing palliative treatment. OUTCOMES: The patients died of tumor progression on June 28, 2021. LESSONS: The testicular metastasis of colorectal cancer is a sign of peritoneum and multiple metastases. When the testicular metastasis occurs in colorectal cancer patients, it usually indicates that the patient has a poor prognosis.

Systematic Comparison and Rational Design of Theophylline Riboswitches for Effective Gene Repression.

Riboswitches are promising regulatory tools in synthetic biology. To date, 25 theophylline riboswitches have been developed for regulation of gene expression in bacteria. However, no one has systematically evaluated their regulatory effects. To promote efficient selection and application of theophylline riboswitches, we examined 25 theophylline riboswitches in Escherichia coli MG1655 and found that they varied widely in terms of activation/repression ratios and expression levels in the absence of theophylline. Of the 20 riboswitches that activate gene expression, only one exhibited a high activation ratio (63.6-fold) and low expression level without theophylline. Furthermore, none of the five riboswitches that repress gene expression were more than 2.0-fold efficient. To obtain an effective repression system, we rationally designed a novel theophylline riboswitch to control a downstream gene or genes by premature transcription termination. This riboswitch allowed theophylline-dependent downregulation of the TurboRFP reporter in a dose- and time-dependent manner. Its performance profile exceeded those of previously described repressive theophylline riboswitches. We then introduced as the second part a RepA tag (protein degradation tag) coding sequence fused at the 5'-terminal end of the turborfp gene, which further reduced protein level, while not reducing the repressive effect of the riboswitch. By combining two tandem theophylline riboswitches with a RepA tag, we constructed a regulatory cassette that represses the expression of the gene(s) of interest at both the transcriptional and posttranslational levels. This regulatory cassette can be used to repress the expression of any gene of interest and represents a crucial step toward harnessing theophylline riboswitches and expanding the synthetic biology toolbox. IMPORTANCE A variety of gene expression regulation tools with significant regulatory effects are essential for the construction of complex gene circuits in synthetic biology. Riboswitches have received wide attention due to their unique biochemical, structural, and genetic properties. Here, we have not only systematically and precisely characterized the regulatory properties of previously developed theophylline riboswitches but also engineered a novel repressive theophylline riboswitch acting at the transcriptional level. By introducing coding sequences of a tandem riboswitch and a RepA protein degradation tag at the 5' end of the reporter gene, we successfully constructed a simple and effective regulatory cassette for gene regulation. Our work provides useful biological components for the construction of synthetic biology gene circuits.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Detection and assessment of dust mite allergens in an indoor environment in Anhui, China.

Dust in the home environment is thought to be a potential trigger for increasing allergic diseases, such as allergic rash, rhinitis, asthma, and other conditions, associated with dust mites. To verify the status of dust mite prevalence in indoor surroundings, we collected 189 dust samples from the air conditioner filters (n = 75) and floors (n = 114) of households, schools, and hotels in the Anhui area, China. All samples were measured for dust mite breeding rate and breeding density under light microscopy and analyzed for dust mite species Dermatophagoides farinae 1 (Der f 1) and Dermatophagoides pteronyssinus 1 (Der p 1) allergen using enzyme-linked immunosorbent assay (ELISA). The dust mite breeding rates were 34.67% (26/75) and 20.18% (23/114), respectively, in the dust samples from the floor and air conditioning filters. The breeding density was the highest in households (10/g), followed by schools (9/g) and hotels (4/g). ELISA indicated that the allergen threshold (2.0 µg/g dust) of Der f 1 was exceeded in only two samples and Der p 1 in one sample. Additionally, a questionnaire was used to investigate the health knowledge on allergic diseases involved in indoor facilities, finding that most allergy sufferers were aware that indoor dust might be responsible for their conditions. The findings suggest that regular maintenance of indoor hygiene and cleaning of air-conditioning filters should reduce the risks of exposure to indoor allergens.

Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review.

BACKGROUND: Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. CASE PRESENTATION: A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. CONCLUSIONS: Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation.

Stimulator of interferon genes (STING) pathway activation predicts the effectiveness of targeting the PD-1/PD-L1 axis in lung cancer. Active IFN-γ signaling is a common feature in tumors that respond to PD-1/PD-L1 blockade. The connection between IFN-γ and STING signaling in cancer cells has not been documented. We showed that IFN-γ caused DNA damage and the accumulation of cytosolic dsDNA, leading to the activation of the cGAS- and IFI16-dependent STING pathway in lung adenocarcinoma cells. IFN-γ-induced iNOS expression and nitric oxide production were responsible for DNA damage and STING activation. Additional etoposide treatment enhanced IFN-γ-induced IFN-ß and CCL5 expression. Tumor-infiltrating T cells stimulated with a combination of anti-CD3 and anti-PD-1 antibodies caused STING activation and increased IFN-ß and CCL5 expression in lung adenocarcinoma. These effects were abrogated by the addition of an IFN-γ neutralizing antibody. Our results suggest that the activation of tumor-infiltrating T cells could alter the tumor microenvironment via the IFN-γ-mediated activation of STING signaling in cancer cells.

The Prognostic Value of GNG7 in Colorectal Cancer and Its Relationship With Immune Infiltration.

Background: G Protein Subunit Gamma 7 (GNG7) is an important gene that regulates cell proliferation and induces apoptosis. However, the correlation between GNG7 expression and immune infiltration as well as patient prognosis of colorectal cancer (CRC) remains unclear. Methods: The GNG7 expression differences between tumor tissues and normal tissues were explored via the Oncomine database, Tumor Immune Estimation Resource (TIMER) site and UALCAN database. Then, the influence of GNG7 on clinical prognosis were evaluated, using the PrognoScan database. In addition, the relationship between GNG7 and tumor-related immune infiltration as well as gene marker sets of immune infiltration was investigated via TIMER, TISIDB and GEPIA. Results: We found that GNG7 expression was down-regulated in multiple malignant tumors including colorectal cancer (CRC) and the GNG7 expression was associated with tumor stage, histology subtype, lymph node metastasis and poor prognosis in colorectal cancer (CRC). In addition, the expression of GNG7 was significantly associated with infiltration level of multiple immune cells, immunomodulatory factors as well as part of the immune cell markers. Conclusion: GNG7 displays validated prognostic value in CRC and was associated with its immune cell infiltration and immunoregulation. These results suggest that GNG7 is a potential prognostic marker and is associated with tumor immune infiltration, thus providing a new perspective for the immunotherapy of CRC.

Assessment of myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices: a prospective study. / å¿ƒè‚ŒåšåŠŸå‚æ•°è¯„ä¼°é‡åº¦å­ç—«å‰æœŸå­•å¦‡å­ä»£æ–°ç”Ÿå„¿æœŸå¿ƒè‚ŒæŸä¼¤çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To evaluate myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices. METHODS: A prospective cohort study was performed on 25 preterm infants born to the pregnant women with severe preeclampsia from June 2020 to April 2021 (severe preeclampsia group), and 25 preterm infants born to the pregnant women without severe complications in pregnancy were enrolled as the control group. Echocardiography was performed within 24 hours and at 48-72 hours and 14-28 days after birth to measure conventional parameters. Two-dimensional speckle-tracking echocardiography was performed to construct a noninvasive left ventricular pressure-strain loop based on two-dimensional myocardial strain and left ventricular systolic pressure noninvasively measured, so as to calculate myocardial work indices. RESULTS: Compared with the control group, the severe preeclampsia group had significant reductions in left ventricular global work index and global constructive work within 24 hours after birth (P<0.05), a significant reduction in left ventricular global work efficiency and a significant increase in global waste work at 48-72 hours after birth (P<0.05), and a significant reduction in left ventricular global work efficiency at 14-28 days after birth (P<0.05). CONCLUSIONS: Subclinical myocardial injury persists in the neonatal period in preterm infants born to pregnant women with severe preeclampsia.

Effect of Plant-Derived n-3 Polyunsaturated Fatty Acids on Blood Lipids and Gut Microbiota: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Several cardioprotective mechanisms attributed to n-3 polyunsaturated fatty acids (PUFAs) have been widely documented. Significant interest has recently focused on the role of human gut microbiota in metabolic disorders. However, the role of plant-derived n-3 PUFAs on blood lipid profiles is controversial and the effect on gut microbiota is still unclear. OBJECTIVES: We aimed to perform a double-blind randomized controlled trial to test the effect of plant-derived n-3 PUFAs on the blood lipids and gut microbiota of patients with marginal hyperlipidemia. METHODS: According to the inclusion and exclusion criteria, 75 participants with marginal hyperlipidemia were randomly assigned to the intervention group (supplied with n-3 PUFA-enriched plant oil) or control group (supplied with corn oil), respectively, for a 3-month treatment. Participants and assessors were blinded to the allocation. The primary outcomes of the trial were the changes in serum lipid levels. Secondary outcomes were changes in gut microbiota and metabolites. For the primary outcomes, we conducted both an intent-to-treat (ITT) analysis and a per protocol (PP) analysis. For the secondary outcomes, we only conducted the PP analysis among the participants who provided fecal sample. RESULTS: Fifty-one participants completed the trial. Relative to the control group, the n-3 PUFA supplementation resulted in significant reduction in total cholesterol (TC) levels (-0.43 mmol/L, 95% CI-0.84 to-0.01 mmol/L, P < 0.05). The n-3 PUFA supplementation was also associated with significantly increased relative abundance of Bacteroidetes in phylum level (P < 0.01; false discovery rate (FDR) corrected p = 0.11), and decreased the ratio between Firmicutes and Bacteroidetes (P < 0.05; FDR corrected p = 0.16). At genus level, the intervention of plant derived n-3 PUFAs resulted in a significant decrease in relative abundance of Phascolarctobacterium (P < 0.01; FDR corrected p = 0.18) and Veillonella (P < 0.01; FDR corrected p = 0.18) after the intervention. CONCLUSIONS: Our results demonstrated that plant-derived n-3 PUFAs beneficially affected the serum levels of TC and decreased the ratio between Firmicutes and Bacteroidetes during the 12-week intervention period, which might confer advantageous consequences for lipid metabolism and intestinal health.

Achieving Long Distance Sensing Using Semiconductor Laser with Optical Feedback by Operating at Switching Status.

In this study, a novel distance sensing method is presented by using a semiconductor laser (SL) with optical feedback (OF) and operating the SL at a switching status happened between two nonlinear dynamic states (stable state and period-one state). In this case, without the need for any electronic or optical modulation devices, the laser intensity can be modulated in a square wave form due to the switching via utilizing the inherent SL dynamics. The periodicity in the switching enables us to develop a new approach for long-distance sensing compared to other SL with OF-based distance measurement systems and lift the relevant restrictions that existed in the systems. Moreover, the impact of system controllable parameters on the duty cycle of the square wave signals generated was investigated on how to maintain the proposed system robustly operating at the switching status. Both simulation and experiment verified the proposed sensing approach.

Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-ß/Smad Signaling.

BACKGROUND: Troponin C-1 (TNNC1) has been previously characterized as an oncogenic gene. AIMS: This study aimed to reveal the roles of TNNC1 in gastric cancer and the potential underlying mechanisms. METHODS: TNNC1 siRNAs and TNNC1 overexpression plasmid were used to alter its expression in AGS, MKN45, and HGC-27 cells. CCK-8 assay, colony formation, EdU assay, flow cytometry, transwell assay, and scratch test were conducted to measure the phenotype changes. In vivo effects of TNNC1 silence were confirmed by using a xenograft mouse model. Bioinformatics analysis was conducted to screen out the transcription factor and downstream signaling of TNNC1. RESULTS: TNNC1 was highly expressed in gastric cancer tissues and cell lines, and its expression was associated with poor prognosis. TNNC1 silence suppressed the proliferation, migration, and invasion of AGS and MKN45 cells. However, TNNC1 silence induced apoptosis by mediating the cleavage of caspase-3 and caspase-9. Overexpression of TNNC1 in HGC-27 cells led to the contrary effects. The anti-tumor effects of TNNC1 silence were also confirmed in a xenograft animal model. E2F1 was validated as an upstream transcription factor of TNNC1. Effects of TNNC1 silence on AGS cell migration and invasion were attenuated by E2F1 overexpression. Besides, TGF-ß/Smad was a downstream signaling pathway of TNNC1. The anti-tumor impacts of TNNC1 silence were weaken by SB431542 (a specific inhibitor of TGF-ß signaling) while accelerated by TGF-ß. CONCLUSION: TNNC1 activated by E2F1 functioned as an oncogenic gene through regulating TGF-ß/Smad signaling. TNNC1 was suggested as a potential molecular drug target of gastric cancer.

Assessment of myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To evaluate myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices.@*METHODS@#A prospective cohort study was performed on 25 preterm infants born to the pregnant women with severe preeclampsia from June 2020 to April 2021 (severe preeclampsia group), and 25 preterm infants born to the pregnant women without severe complications in pregnancy were enrolled as the control group. Echocardiography was performed within 24 hours and at 48-72 hours and 14-28 days after birth to measure conventional parameters. Two-dimensional speckle-tracking echocardiography was performed to construct a noninvasive left ventricular pressure-strain loop based on two-dimensional myocardial strain and left ventricular systolic pressure noninvasively measured, so as to calculate myocardial work indices.@*RESULTS@#Compared with the control group, the severe preeclampsia group had significant reductions in left ventricular global work index and global constructive work within 24 hours after birth (P<0.05), a significant reduction in left ventricular global work efficiency and a significant increase in global waste work at 48-72 hours after birth (P<0.05), and a significant reduction in left ventricular global work efficiency at 14-28 days after birth (P<0.05).@*CONCLUSIONS@#Subclinical myocardial injury persists in the neonatal period in preterm infants born to pregnant women with severe preeclampsia.

IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells.

Interferon-gamma (IFN-γ) is a major effector molecule of immunity and a common feature of tumors responding to immunotherapy. Active IFN-γ signaling can directly trigger apoptosis and cell cycle arrest in human cancer cells. However, the mechanisms underlying these actions remain unclear. Here, we report that IFN-γ rapidly increases protein synthesis and causes the unfolded protein response (UPR), as evidenced by the increased expression of glucose-regulated protein 78, activating transcription factor-4, and c/EBP homologous protein (CHOP) in cells treated with IFN-γ. The JAK1/2-STAT1 and AKT-mTOR signaling pathways are required for IFN-γ-induced UPR. Endoplasmic reticulum (ER) stress promotes autophagy and restores homeostasis. Surprisingly, in IFN-γ-treated cells, autophagy was impaired at the step of autophagosome-lysosomal fusion and caused by a significant decline in the expression of lysosomal membrane protein-1 and -2 (LAMP-1/LAMP-2). The ER stress inhibitor 4-PBA restored LAMP expression in IFN-γ-treated cells. IFN-γ stimulation activated the protein kinase-like ER kinase (PERK)-eukaryotic initiation factor 2a subunit (eIF2α) axis and caused a reduction in global protein synthesis. The PERK inhibitor, GSK2606414, partially restored global protein synthesis and LAMP expression in cells treated with IFN-γ. We further investigated the functional consequences of IFN-γ-induced ER stress. We show that inhibition of ER stress significantly prevents IFN-γ-triggered apoptosis. CHOP knockdown abrogated IFN-γ-mediated apoptosis. Inhibition of ER stress also restored cyclin D1 expression in IFN-γ-treated cells. Thus, ER stress and the UPR caused by IFN-γ represent novel mechanisms underlying IFN-γ-mediated anticancer effects. This study expands our understanding of IFN-γ-mediated signaling and its cellular actions in tumor cells.