Nitrate Chemodenitrification by Iron Sulfides to Ammonium under Mild Conditions and Transformation Mechanism.

Autotrophic denitrification utilizing iron sulfides as electron donors has been well studied, but the occurrence and mechanism of abiotic nitrate (NO3-) chemodenitrification by iron sulfides have not yet been thoroughly investigated. In this study, NO3- chemodenitrification by three types of iron sulfides (FeS, FeS2, and pyrrhotite) at pH 6.37 and ambient temperature of 30 °C was investigated. FeS chemically reduced NO3- to ammonium (NH4+), with a high reduction efficiency of 97.5% and NH4+ formation selectivity of 82.6%, but FeS2 and pyrrhotite did not reduce NO3- abiotically. Electrochemical Tafel characterization confirmed that the electron release rate from FeS was higher than that from FeS2 and pyrrhotite. Quenching experiments and density functional theory calculations further elucidated the heterogeneous chemodenitrification mechanism of NO3- by FeS. Fe(II) on the FeS surface was the primary site for NO3- reduction. FeS possessing sulfur vacancies can selectively adsorb oxygen atoms from NO3- and water molecules and promote water dissociation to form adsorbed hydrogen, thereby forming NH4+. Collectively, these findings suggest that the NO3- chemodenitrification by iron sulfides cannot be ignored, which has great implications for the nitrogen, sulfur, and iron cycles in soil and water ecosystems.

Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer.

BACKGROUND: Gastric cancer is a global health concern that poses a significant threat to human well-being. AIM: To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer. METHODS: Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined. RESULTS: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients. CONCLUSION: CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.

Acetyl-11-keto-beta-boswellic acid modulates macrophage polarization and Schwann cell migration to accelerate spinal cord injury repair in rats.

BACKGROUND: Inhibiting secondary inflammatory damage caused by glial cells and creating a stable microenvironment is one of the main strategies to investigate drugs for the treatment of spinal cord injury. Acetyl-11-keto-beta-boswellic acid (AKBA) is the active component of the natural drug boswellia, which has anti-inflammatory and antioxidant effects and offers a possible therapeutic option for spinal cord injury. METHODS: In this study, a spinal cord injury model was established by crushing spinal cord, respectively, to detect the M1 macrophage inflammatory markers: iNOS, TNF-α, IL-1ß, and the M2 macrophage markers CD206, ARG-1, IL-10, and the detection of antioxidant enzymes and MDA. In vitro, macrophages were cultured to verify the main mechanism of the macrophage switch from Nrf2/HO-1 to M2 type by flow cytometry, immunofluorescence, and other techniques. Macrophage and Schwann cell co-culture validated the migration mechanism of Schwann cells promoted by AKBA. RESULTS: AKBA significantly enhanced the antioxidant enzyme activities of CAT, GSH-Px, T-AOC, and SOD, reduced MDA content, and reduced oxidative damage caused by spinal cord injury via the Nrf2/HO-1 signaling pathway; AKBA mediates Nrf2/HO-1/IL-10, converts macrophages from M1 to M2 type, reduces inflammation, and promotes Schwann cell migration, thereby accelerating the repair of spinal cord injury in rats. CONCLUSIONS: Our work demonstrates that AKBA can attenuate oxidative stress as well as the secondary inflammatory injury caused by macrophages after SCI, promote Schwann cell migration to the injury site, and thus accelerate the repair of the injured spinal cord.

ALKBH5 facilitates the progression of infantile hemangioma by increasing FOXF1 expression in a m6A-YTHDF2 dependent manner to activate HK-2 signaling.

Alkylation repair homolog protein 5 (ALKBH5) is reported to participate in infantile hemangioma (IH) progression. However, the underlying mechanism of ALKBH5 in IH remains unclear. Using qRT-PCR and Western blotting, ALKBH5, forkhead box F1 (FOXF1) and hexokinase 2 (HK-2) expressions in IH tissues and IH-derived endothelial cells XPTS-1 were assessed. The Me-RIP assay was used to analyze FOXF1 m6A level. CCK8, colony formation, flow cytometry and transwell assays were employed to determine IH cell viability, proliferation, apoptosis, migration and invasion. The interactions between YTH (YT521-B homology) domain 2 (YTHDF2), FOXF1 and HK-2 were analyzed by RIP, dual luciferase reporter gene assay and/or ChIP assay. The in vivo IH growth was evaluated in immunocompromised mice. FOXF1 was overexpressed in IH tissues, and its silencing inhibited IH cell proliferation, migration and invasion whereas promoting cell apoptosis in vitro. ALKBH5 upregulation facilitated FOXF1 mRNA stability and expression in IH cells in a m6A-YTHDF2-dependent manner. FOXF1 downregulation reversed the impact of ALKBH5 upregulation on IH cellular phenotypes. It also turned out that FOXF1 positively regulated HK-2 expression in IH cells through interacting with the HK-2 promoter. HK-2 upregulation abolished FOXF1 knockdown's inhibition on IH cell aggressive behaviors. ALKBH5 or FOXF1 silencing suppressed IH tumor development via HK-2 signaling in immunocompromised mice. ALKBH5 promoted FOXF1 expression m6A-YTHDF2 dependently, which in turn elevated HK-2 expression, thereby accelerating IH development.

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China.

Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option.

Assessing Serplulimab's Value in Treating Advanced Esophageal Cancer in China In China, esophageal cancer patients often need chemotherapy due to late diagnosis. Serplulimab, an expensive new treatment, is not cost-effective when combined with chemotherapy for most patients. However, for specific patient groups with a PD-L1 expression CPS ⩾ 10, it is both effective and affordable. This finding helps health care leaders create better pricing strategies.

RPL22L1, a novel candidate oncogene promotes temozolomide resistance by activating STAT3 in glioblastoma.

Aggressiveness and drug resistance are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ resistance in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.

Neoadjuvant sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: a single-arm phase 2 trial.

In this multicenter, single-arm phase 2 trial (ChiCTR1900024428), patients with locally advanced gastric/gastroesophageal junction cancers receive one cycle of sintilimab (anti-PD1) and chemotherapy (S-1 and nab-paclitaxel), followed by 5 weeks of concurrent chemoradiotherapy and sintilimab, and another cycle of sintilimab and chemotherapy thereafter. Surgery is preferably scheduled within one to three weeks, and three cycles of adjuvant sintilimab and chemotherapy are administrated. The primary endpoint is the pathological complete response. Our results meet the pre-specified primary endpoint. Thirteen of 34 (38.2%) enrolled patients achieve pathological complete response (95% CI: 22.2-56.4). The secondary objectives include disease-free survival (DFS), major pathological response, R0 resection rate, overall survival (OS), event-free survival (EFS), and safety profile. The median DFS and EFS were 17.0 (95%CI: 11.1-20.9) and 21.1 (95%CI: 14.7-26.1) months, respectively, while the median OS was not reached, and the 1-year OS rate was 92.6% (95%CI: 50.1-99.5%). Seventeen patients (50.0%) have grade ≥3 adverse events during preoperative therapy. In prespecified exploratory biomarker analysis, CD3+ T cells, CD56+ NK cells, and the M1/M1 + M2-like macrophage infiltration at baseline are associated with pathological complete response. Here, we show the promising efficacy and manageable safety profile of sintilimab in combination with concurrent chemoradiotherapy for the perioperative treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma.

Malnutrition and visceral obesity predicted adverse short-term and long-term outcomes in patients undergoing proctectomy for rectal cancer.

BACKGROUND: To the best of our knowledge, no previous studies have explored the relationship between visceral obesity and malnutrition. Therefore, this study has aimed to investigate the association between them in patients with rectal cancer. METHODS: Patients with rectal cancer who underwent proctectomy were included. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM). Visceral obesity was measured using computed tomography (CT). The patients were classified into four groups according to the presence of malnutrition or visceral obesity. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for postoperative complications. Univariate and multivariate cox regression analyses were performed to evaluate the risk factors for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves and log-rank tests were performed for the four groups. RESULTS: This study enrolled 624 patients. 204 (32.7%) patients were included in the well-nourished non-visceral obesity (WN) group, 264 (42.3%) patients were included in the well-nourished visceral obesity (WO) group, 114 (18.3%) patients were included in the malnourished non-visceral obesity (MN) group, and 42 (6.7%) patients were included in the malnourished visceral obesity (MO) group. In the multivariate logistic regression analysis, the Charlson comorbidity index (CCI), MN, and MO were associated with postoperative complications. In the multivariate cox regression analysis, age, American Society of Anesthesiologists (ASA) score, tumor differentiation, tumor node metastasis (TNM), and MO were associated with worsened OS and CSS. CONCLUSIONS: This study demonstrated that the combination of visceral obesity and malnutrition resulted in higher postoperative complication and mortality rates and was a good indicator of poor prognosis in patients with rectal cancer.

Network pharmacology integrated with experimental validation revealed potential molecular mechanisms of Camellia nitidissima C. W. Chi in the treatment of lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Camellia nitidissima C.W.Chi (CNC), an ethnomedicine mainly distributed in Southern China's Guangxi Zhuang Autonomous Region, is known as "Panda in plants" and "Camellias Queen" due to its golden blossom. CNC has been applied as a traditional folk medicine in cancer therapy. AIM OF THE STUDY: This study utilized network pharmacology analysis combined with experimental validation to identify the substance basis and potential molecular mechanism of CNC against lung cancer. MATERIALS AND METHODS: The active ingredients of CNC were identified based on published literature. The associated potential targets of CNC in lung cancer treatment were predicted using integrated network pharmacology analysis and molecular docking. The underlying molecular mechanism of CNC in lung cancer were validated in human lung cancer cell lines. RESULTS: A total of 30 active ingredients and 53 targets of CNC were screened. An enrichment analysis of Gene Ontology (GO) revealed that the effects of CNC in lung cancer mainly involve protein binding, regulation of cell proliferation and apoptosis, and signal transduction. KEGG pathways analysis suggested that CNC might exert cancer suppression effects mainly through pathways in cancer, PI3K/AKT signaling pathway. Molecular docking revealed that CNC has high affinity for binding of EGFR, SRC, AKT1, and CCND1 to the key active ingredients including luteolin, kaempferol, quercetin, eriodictyol and 3'4-O-dimethylcedrusin. In in vitro experiments, CNC played the inhibitory roles in lung cancer cells by inducing cell apoptosis, causing G0/G1 and S cell cycle arrest, increasing intracellular ROS levels, and promoting the apoptotic proteins Bax and Caspase-3. Meanwhile, CNC also regulated the expression of core proteins EGFR, SRC, and AKT. CONCLUSION: These results comprehensively clarified the associated substance basis and underlying molecular mechanism of CNC against lung cancer, which would be contributed to develop promising anti-cancer pharmaceuticals or therapeutic approaches for lung cancer therapy.

The emerging role of lysine succinylation in ovarian aging.

BACKGROUND: Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc. METHODS: The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level. RESULTS: Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc. CONCLUSION: The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.

The ovarian-related effects of polystyrene nanoplastics on human ovarian granulosa cells and female mice.

Nanoplastics (NPs) have recently emerged in the context of global plastic pollution. They may be more toxic than macroplastics litter and microplastic fragments due to its abundances, tiny sizes, and cellular accessibility. The female reproductive toxicity of NPs has been widely documented for aquatic animals, but their effects and underlying mechanisms remain poorly understood in mammals. This study aimed to explore the effects of NPs on female reproduction using human ovarian granulosa cells (GCs) and female mice. The accumulation of polystyrene NPs (PS-NPs) in human granulosa-like tumor cells (KGN cells) and the ovaries of female Balb/c mice were evaluated by exposure to fluorescent PS-NPs. Proliferation and apoptosis, reactive oxygen species (ROS), and Hippo signaling pathway-related factors were analyzed in KGN cells. In addition, fertility rate, litter size, ovarian weight and microstructure, follicle development, serum level of anti-Mullerian hormone, and apoptosis in ovaries were examined in female mice. Here, the PS-NPs can penetrate the KGN cells and accumulate in the ovaries. In vitro, 100 µg/ml PS-NPs inhibited proliferation, induced apoptosis, accumulated ROS, activated three key regulators of the Hippo signaling pathway (MST1, LATS1, and YAP1), and downregulated the mRNA levels of CTGF and Cyr61 in KGN cells. Furthermore, salidroside, an antioxidative compound extracted from Rhodiola rosea, alleviated the damage of PS-NPs to KGN and inhibited the activation of the Hippo signal pathway. In vivo, exposure to 1 mg/day PS-NPs resulted in decreased fertility, abnormal ovarian function, and increased ovarian apoptosis in female mice. Overall, our data suggest that PS-NPs cause granulosa cell apoptosis and affect ovarian functions, leading to reduced fertility in female mice, by inducing oxidative stress and dysregulating the Hippo pathway.

Increased peripapillary capillaries in patients with acute leukemia by using optical coherence tomography angiography.

PURPOSE: To evaluate the radial peripapillary capillary vessel density (RPC-VD) and thickness of the retinal nerve fiber layer (RNFL) in acute leukemia (AL) and the associations of these characteristics with blood laboratory parameters. METHODS: A cross-sectional study was performed at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from February 2019 to April 2022. Sixty eyes of 30 patients diagnosed with AL and sixty eyes of 30 matched healthy controls were included. Optical coherence tomography angiography (OCTA) in the 4.5-mm Angio Disc scan mode and the Ganglion cell complex scan mode were performed for all participants. Correlation analyses were used to examine the associations of RPC-VD and RNFL with blood laboratory parameters. RESULTS: Patients in the AL group had significantly increased RPC-VD in the whole-image (51.42±0.35 vs. 49.52±0.36) and peripapillary fields (53.90±0.43 vs. 51.17±0.50) compared with people in the control group (all P<0.001), while no difference was found for RPC-VD in the inside optic disk fields in the two groups. The RNFL in the AL group was significantly thicker than that in the control group (131.10±3.89 µm vs. 115.03±2.22 µm, P<0.05). Complete blood count (CBC) parameters, including red blood cells, hemoglobin and hematocrit, had a significant negative correlation with RPC-VD and RNFL (all P <0.05). CONCLUSION: An increased RPC-VD and a thicker RNFL are evidence of fundus changes in patients with early-stage AL, and these metrics may be related to decreases in red blood cells, hemoglobin and hematocrit.

P-Y/G@NHs sensitizes non-small cell lung cancer cells to radiotherapy via blockage of the PI3K/AKT signaling pathway.

Radioresistance represents a common phenomenon found in cancer treatment. Herein, the current study sought to evaluate the effects of a nanodrug delivery system of YSAYPDSVPMMS (YSA) peptide-modified gold nanoparticles-dextran-based hydrogel loaded with paclitaxel-succinic anhydride (P-Y/G@NHs) on non-small cell lung cancer (NSCLC) cell radiosensitivity. Firstly, utilizing the coupling reaction and layer-by-layer assembly technique, P-Y/G@NHs was prepared. The therapeutic effects of the P-Y/G@NHs in NSCLC cells in relation to the PI3K/AKT signaling pathway were examined by assessing the colony formation, apoptosis, and reactive oxygen species (ROS) generation of A549 cells under 10 Gy X-rays irradiation. Moreover, A549 tumor-bearing mice were generated to further validate the therapeutic effect in vivo. We confirmed the successful conjugation of the nanocomposite. Under 10 Gy X-rays irradiation, P-Y/G@NHs reduced the number of colonies of A549 cells, while inducing both cell apoptosis and ROS production. Moreover, P-Y/G@NHs enhanced the radiosensitivity of A549 cells by inhibiting the PI3K/AKT signaling pathway. In vivo fluorescence experiments validated that P-Y/G@NHs effectively-targeted and accumulated at the tumor site in nude mice, thus augmenting the radiosensitivity of tumors without significant immune toxicity or side effects. Conclusively, our findings highlighted that P-Y/G@NHs significantly enhanced the radiosensitivity of NSCLC cells by repressing the PI3K/AKT signaling pathway.

Sunlight-Driven Production of Reactive Oxygen Species from Natural Iron Minerals: Quantum Yield and Wavelength Dependence.

Photochemically generated reactive oxygen species (ROS) play numerous key roles in earth's surface biogeochemical processes and pollutant dynamics. ROS production has historically been linked to the photosensitization of natural organic matter. Here, we report the photochemical ROS production from three naturally abundant iron minerals. All investigated iron minerals are photoactive toward sunlight irradiation, with photogenerated currents linearly correlated with incident light intensity. Hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) are identified as the major ROS species, with apparent quantum yields ranging from 1.4 × 10-8 to 3.9 × 10-8 and 5.8 × 10-8 to 2.5 × 10-6, respectively. Photochemical ROS production exhibits high wavelength dependence, for instance, the •OH quantum yield decreases with the increase of light wavelength from 375 to 425 nm, and above 425 nm it sharply decreases to zero. The temperature shows a positive impact on •OH production, with apparent activation energies ranging from 8.0 to 17.8 kJ/mol. Interestingly, natural iron minerals with impurities exhibit higher ROS production than their pure crystal counterparts. Compared with organic photosensitizers, iron minerals exhibit higher wavelength dependence, higher selectivity, lower efficiency, and long-term stability in photochemical ROS production. Our study highlights natural inorganic iron mineral photochemistry as a ubiquitous yet previously overlooked source of ROS.

The geriatric nutritional risk index is an effective tool to detect GLIM-defined malnutrition in rectal cancer patients.

Background: This study aimed to investigate the value of the Geriatric Nutritional Risk Index (GNRI), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI) scores in detecting malnutrition in patients with rectal cancer; the Global Leadership Initiative on Malnutrition (GLIM) was used as the reference criterion. Materials and methods: This study included patients with rectal cancer who underwent proctectomy. GNRI, PNI, and ALI were calculated to detect the GLIM-defined malnutrition using the Receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression analyses were used to evaluate the association between the nutritional tools and postoperative complications. Kaplan-Meier survival curves, log-rank tests, and univariate and multivariate Cox regression analyses were used to clarify the relationship between nutritional tools and overall survival (OS). Results: This study enrolled 636 patients with rectal cancer. The GNRI demonstrated the highest sensitivity (77.8%), pretty specificity (69.0%), and the largest AUC (0.734). The GNRI showed good property in predicting major postoperative complications. All three nutritional tools were independent predictors of OS. Conclusion: The GNRI can be used as a promising alternative to the GLIM and is optimal in perioperative management of patients with rectal cancer.

Occupational health and safety: measurement and analysis of the electromagnetic radiation produced by radiofrequency devices for rejuvenation.

With the ongoing development of cosmetic technology, many different types of radiofrequency (RF) devices are widely used for face and body rejuvenation. These, like many other high-power devices, may emit excessive electromagnetic radiation into the surrounding environment. Long-term exposure to this environment can lead to poor health outcomes; therefore, it is important to measure and analyze the electromagnetic radiation levels for the health and safety of therapists. A handheld electronic electromagnetic radiation measuring instrument was used to measure the electric and magnetic field strengths. All results were analyzed using the R software (R Core Team, 2021-02-15). We found that the monopolar and unipolar RF devices that we measured from, in this study, could produce large amounts of electromagnetic radiofrequency emissions during operation, whereas the microneedle RF (bipolar RF) device emitted relatively lower amounts (P < 0.01). The strength of electromagnetic radiation is related to power and distance; it increases with power and decreases with distance. This study proved that certain RF devices for rejuvenation could cause severe electromagnetic radiofrequency pollution. The occupational health and safety of therapists require more attention, and effective protective measures need to be taken immediately.

A prognostic signature model for unveiling tumor progression in lung adenocarcinoma.

A more accurate prognosis is important for clinical treatment of lung adenocarcinoma. However, due to the limitation of sample and technical bias, most prognostic signatures lacked reproducibility, and few were applied to clinical practice. In addition, understanding the molecular driving mechanism is indispensable for developing more promising therapies for lung adenocarcinoma. Here, we built an unbiased prognostic significance model to perform an integrative analysis, including differentially expressed genes and clinical data with lung adenocarcinoma patients from TCGA. Multivariable Cox proportional hazards model with the Lasso penalty and 10-fold cross-validate were used to identify the best gene signature. We generated a 17-gene signature for prognostic risk prediction based on the overall survival time of lung adenocarcinoma patients. To further test the model's predictive ability, we have applied an independent GEO database to verify the predictive ability of prognostic signature. The model can more objectively describe several biological processes related to tumors and reveal important molecular mechanisms in tumor development by GO and KEGG analysis. Furthermore, differential expression analysis by GSEA revealed that tumor microenvironments such as ER stress, exosome, and immune microenvironment were enriched. Using single-cell RNA sequence technology, we found that risk score was positively correlated with lung adenocarcinoma marker genes and copy number variation but negatively correlated with lung epithelial marker genes. High-risk cell populations with the model had stronger cancer stemness and tumor-related pathway activation. As we expected, the risk score was in accordance with the malignancy of each cluster from tumor progression. In conclusion, the risking model established in this study is more reliable than others in evaluating the prognosis of LUAD patients.

Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma.

Background: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo. Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation. Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD). Results: Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 108 iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice. Conclusions: The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo.

Impact of metabolic syndrome on the short- and long-term outcomes for the elderly patients with gastric cancer after radical gastrectomy.

BACKGROUND: Metabolic syndrome (MetS) and gastric cancer are age-related diseases, and their incidence rates have risen in past decades. However, few studies have examined the relationship between MetS and the prognosis of elderly patients who underwent radical gastrectomy, and the conclusions remain controversial. METHODS: We conducted a prospective study of elderly patients who underwent radical gastrectomy for gastric cancer from August 2014 to February 2018. MetS was defined based on visceral fat area (VFA) instead of BMI or waist circumference. Receiver operating characteristic curve analysis was used to determine the cutoff values for VFA. RESULTS: A total of 585 patients were included in this study. The optimal cutoff values for VFA were 96.1 cm2 for men and 105.2 cm2 for women, and 212 patients were diagnosed with MetS. The patients with MetS suffered significantly more postoperative complications than those without MetS (37.3% versus 21.4%, P < 0.001). The multivariable logistic regression analysis demonstrated that MetS (OR 2.923, P < 0.001), BMI < 18.5 kg/m2 (OR 2.086, P = 0.045), cardiac tumor (OR 1.865, P = 0.013), and Nutritional Risk Screening 2002 scores ≥ 3 (OR 1.654, P = 0.015) were independent risk factors for postoperative complications. During a median follow-up period of 56.4 months, the MetS group and the non-MetS group had comparable overall survival and disease-specific survival. CONCLUSIONS: MetS was an independent risk factor for complications of the elderly patients after radical gastrectomy, but had no influence on long-term survival.

Proteomics analysis of cancer tissues identifies IGF2R as a potential therapeutic target in laryngeal carcinoma.

Background: Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease's pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer. Methods: To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined. Results: In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC. Conclusion: These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.