Riboflavin Attenuates Fluoride-Induced Testicular Injury via Interleukin 17A-Mediated Classical Pyroptosis.

Male reproductive toxicity of fluoride is of great concern worldwide, yet the underlying mechanism is unclear. Pyroptosis is a novel mode of inflammatory cell death, and riboflavin with anti-inflammatory properties has the potential to protect against fluoride damage. However, it is unknown whether pyroptosis is involved in fluoride-induced testicular injury and riboflavin intervention. Here, we first found that riboflavin could alleviate fluoride-caused lower sperm quality and damaged testicular morphology by reducing pyroptosis based on a model of ICR mice treated with NaF (100 mg/L) and/or riboflavin supplementation (40 mg/L) via drinking water for 13 weeks. And then, together with the results of in vitro Leydig cell modelsm it was confirmed that the pyroptosis occurs predominantly through classical NLRP3/Caspase-1/GSDMD pathway. Furthermore, our results reveal that interleukin-17A mediates the process of pyroptosis in testes induced by fluoride and riboflavin attenuation according to the results of our established models of riboflavin- and/or fluoride-treated IL-17A knockout mice. The results not only declare a new mechanism by which fluoride induces testicular injury via interleukin 17A-mediated classical pyroptosis but also provide evidence for the potential clinical application of riboflavin as an effective therapy for fluoride toxicity.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer.

Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib.

Bacillus subtilis improves antioxidant capacity and optimizes inflammatory state in broilers.

OBJECTIVE: Bacillus subtilis, a kind of probiotic with broad-spectrum antibacterial function, was commonly used in livestock and poultry production. Recent research suggested that Bacillus subtilis may have antioxidant properties and improve immune response. This study aimed to verify the probiotic function of Bacillus subtilis in the production of broiler chickens. METHODS: A total of 324 (1-day-old) Arbor Acres broilers were selected and randomly divided into three groups: basal diet group (Ctr Group), basal diet + antibiotic growth promoter group (Ctr + AGP) and basal diet + 0.5% Bacillus subtilis preparation group (Ctr + Bac). The experiment lasted for 42 days. Muscle, serum and liver samples were collected at 42 days for determination. RESULTS: The results showed that Bacillus subtilis could decrease malondialdehyde content in the serum and liver (p<0.05) and increase superoxide dismutase 1 mRNA expression (p<0.01) and total superoxide dismutase (p<0.05) in the liver. In addition, compared with AGP supplementation, Bacillus subtilis supplementation increased interleukin-10 (IL-10) and decreased tumor necrosis factor-α and IL-1ß level in the serum (p<0.05). At 45 minutes after slaughter Ctr + Bac presented a higher a* value of breast muscle than Ctr Group (p<0.05), while significant change in leg muscle was not identified. Moreover, there was no difference in weight, shear force, cooking loss and drip loss of breast and leg muscle between treatments. CONCLUSION: Our results demonstrate that Bacillus subtilis in diet can enhance antioxidant capacity and optimize immune response of broilers.

Hollow CoZnSe@CN nanocage with enzymatic activity for determination of tetracycline using smartphone platforms and virtual reality revealing.

Antibiotic residues in the environment pose a serious threat to ecosystems and human health. Therefore, it is important to develop sensitive and rapid in situ detection methods. In this work, the designed nanozymes, with excellent four enzyme activities, were proved to be constituted of unique hollow nanocage structures (CoZnSe@CN HCs). Based on the peroxidase-like enzymes, a portable colorimetric sensor was constructed for the on-site determination of tetracycline (TC) in real samples. The linear range of TC detection was 0.1-100 µM, and the detection limit was 0.02 µM. At the same time, colorimetric detection and smartphones have also been combined for on-site colorimetric detection of TC. In-depth exploration of the detection mechanism showed that TC could be bound with the material, inhibiting the production of oxidized 3,3',5,5'-tetramethylbenzidine. The sensor was also used for the detection of TC in environmental soil and water samples. This study can provide an intelligent detection method for environmental monitoring.

Novel Synthesis of Phytosterol Ferulate Using Acidic Ionic Liquids as a Catalyst and Its Hypolipidemic Activity.

Phytosterol ferulate (PF) is quantitively low in rice, corn, wheat, oats, barley, and millet, but it is potentially effective in reducing plasma lipids. In this study, PF was synthesized for the first time using acidic ionic liquids as a catalyst. The product was purified, characterized using Fourier transform infrared, mass spectroscopy, and nuclear magnetic resonance, and ultimately confirmed as the desired PF compound. The conversion of phytosterol surpassed an impressive 99% within just 2 h, with a selectivity for PF exceeding 83%. Plasma lipid-lowering activity of PF was further investigated by using C57BL/6J mice fed a high-fat diet as a model. Supplementation of 0.5% PF into diet resulted in significant reductions in plasma total cholesterol, triacylglycerols, and nonhigh-density lipoprotein cholesterol by 13.7, 16.9, and 46.3%, respectively. This was accompanied by 55.8 and 36.3% reductions in hepatic cholesterol and total lipids, respectively, and a 22.9% increase in fecal cholesterol excretion. Interestingly, PF demonstrated a higher lipid-lowering activity than that of its substrates, a physical mixture of phytosterols and ferulic acid. In conclusion, an efficient synthesis of PF was achieved for the first time, and PF had the great potential to be developed as a lipid-lowering dietary supplement.

Repurposing an Antioxidant to Kill Mycobacterium tuberculosis by Targeting the 50S Subunit of the Ribosome.

Tuberculosis and drug-resistant TB remain serious threats to global public health. It is urgent to develop novel anti-TB drugs in order to control it. In addition to redesigning and developing new anti-TB drugs, drug repurposing is also an innovative way to develop antibacterial drugs. Based on this method, we discovered SKQ-1 in the FDA-approved drug library and evaluated its anti-TB activity. In vitro, we demonstrated that SKQ-1 engaged in bactericidal activity against drug-sensitive and -resistant Mtb and confirmed the synergistic effects of SKQ1 with RIF and INH. Moreover, SKQ-1 showed a significant Mtb-killing effect in macrophages. In vivo, both the SKQ-1 treatment alone and the treatment in combination with RIF were able to significantly reduce the bacterial load and improve the survival rate of G. mellonella infected with Mtb. We performed whole-genome sequencing on screened SKQ-1-resistant strains and found that the SNP sites were concentrated in the 50S ribosomal subunit of Mtb. Furthermore, we proved that SKQ-1 can inhibit protein translation. In summary, from the perspective of drug repurposing, we discovered and determined the anti-tuberculosis effect of SKQ-1, revealed its synergistic effects with RIF and INH, and demonstrated its mechanism of action through targeting ribosomes and disrupting protein synthesis, thus making it a potential treatment option for DR-TB.

Construction of CuO/Fe2O3 Nanozymes for Intelligent Detection of Glufosinate and Chlortetracycline Hydrochloride.

In this work, CuO/Fe2O3 nanozymes with high peroxidase-like activity were synthesized by using hydrothermal and calcination methods. The high-resolution transmission electron microscopy (HRTEM) proved that the heterogeneous interface of CuO/Fe2O3 was the main reason for the high enzyme-like activity. Strong interactions of CuO and Fe2O3 were successfully verified by X-ray absorption near-edge structure (XANES) characterization. Experiments and density functional theory (DFT) calculations were also used to explain the increased enzyme activity. The heterogeneous interface acted as the main active center, facilitating the electron transfer from CuO to Fe2O3. A colorimetric and intelligent sensing system was constructed based on deep learning. Using the peroxidase-like activity of CuO/Fe2O3, a platform for glufosinate pesticides and chlortetracycline hydrochloride (CTC) with the signal "on-off-on" changes were established. The limit of detection (LOD) of glufosinate and CTC was 28 and 0.69 µM, respectively. It was successfully applied in the detection of environmental water and soil. This study can provide an intelligent detection method for environmental monitoring.

Nutritional composition, health-promoting effects, bioavailability, and encapsulation of tree peony seed oil: a review.

Tree peony is cultivated worldwide in large quantities due to its exceptional ornamental and medicinal value. In recent years, the edible value of tree peony seed oil (TPSO) has garnered significant attention for its high content of alpha-linolenic acid (ALA, >40%) and other beneficial minor components, including phytosterols, tocopherols, squalene, and phenolics. This review provides a systematic summary of the nutritional composition and health-promoting effects of TPSO, with a specific focus on its digestion, absorption, bioavailability, and encapsulation status. Additionally, information on techniques for extracting and identifying adulteration of TPSO, as well as its commercial applications and regulated policies, is included. Thanks to its unique nutrients, TPSO offers a wide range of health benefits, such as hypolipidemic, anti-obesity, cholesterol-lowering, antioxidant and hypoglycemic activities, and regulation of the intestinal microbiota. Consequently, TPSO shows promising potential in the food and cosmetic industries and should be cultivated in more countries. However, the application of TPSO is hindered by its low bioavailability, poor stability, and limited water dispersibility. Therefore, it is crucial to develop effective delivery strategies, such as microencapsulation and emulsion, to overcome these limitations. In conclusion, this review provides a comprehensive understanding of the nutritional value of TPSO and emphasizes the need for further research on its nutrition and product development.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer.

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer.

BACKGROUND: The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. METHODS: This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan-Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. RESULTS: Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P =0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. CONCLUSIONS: Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.

Corrigendum: Relationship between programmed death ligand 1 expression and other clinicopathological features in a large cohort of gastric cancer patients.

[This corrects the article DOI: 10.3389/fimmu.2022.783695.].

SARS-Cov-2 Spike-S1 Antigen Test Strip with High Sensitivity Endowed by High-Affinity Antibodies and Brightly Fluorescent QDs/Silica Nanospheres.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1α Positive Feedback Loop.

Anti-angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti-angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4-acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF-1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP-sequencing, Ribosome profiling sequencing, RNA-sequencing, and functional studies confirm that NAT10 in turn activates the HIF-1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF-1α positive feedback loop leads to excessive activation of the HIF-1 pathway and induces glycolysis addiction. Combined anti-angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti-angiogenic therapy by combining apatinib with ac4C inhibition.

A small pore black TiO2/-large pore Fe3O4 cascade nanoreactor for chemodynamic/photothermal synergetic tumour therapy.

Various unique spatial structures are often found in the enzymes of biological systems. From the consideration of bionics, it is challenging but meaningful to design nanozymes with distinctive structures to enhance their bioactivities. To explore the relationship between the structure and activity of nanozymes, in this work, a special structural nanoreactor, namely small pore black TiO2 coated/doped large pore Fe3O4 (TiO2/-Fe3O4) loaded with lactate oxidase (LOD), was constructed for chemodynamic and photothermal synergistic therapy. Specifically, LOD loaded on the surface of the TiO2/-Fe3O4 nanozyme alleviates the low level of H2O2 in the tumour microenvironment (TME); the black TiO2 shell with multiple pinhole channels and a large specific surface area not only facilitates LOD loading, but also enhances the affinity of the nanozyme for H2O2; H2O2 is continuously enriched on the surface of the TiO2/-Fe3O4 nanozyme and transmitted to mesoporous Fe3O4, in turn efficiently producing abundant toxic hydroxyl radicals (˙OH) for chemodynamic therapy. Meanwhile, the TiO2/-Fe3O4 nanozyme under 1120 nm laser irradiation has excellent photothermal conversion efficiency (η = 41.9%), and further accelerates the production of ˙OH for amplifying the chemodynamic therapy efficiency. This self-cascading, special structure nanozyme provides a novel strategy for application in highly efficient tumour synergetic therapy.

Who consumes curative care expenditure of medical institutions in Beijing: a case study based on System of Health Accounts 2011.

BACKGROUND: China's health system is challenged by complex health problems experienced by different population groups and caused by multiple diseases. This study examined the distribution of curative care expenditure (CCE) of medical institutions in Beijing using beneficiary characteristics such as residency, gender, age, and disease. Suggestions are presented for the development of health policies. METHODS: A total of 81 medical institutions with approximately 80 million patients in Beijing, China, were selected via a multistage stratified cluster random sampling approach. Based on this sample, the System of Health Accounts 2011 was used to estimate the CCE of medical institutions. RESULTS: The CCE of medical institutions in Beijing was ¥246.93 billion in 2019. The consumption of patients from other provinces was ¥60.04 billion, accounting for 24.13% of the total CCE. The CCE of female consumption (52.01%/¥128.42 billion) exceeded that of male consumption (47.99%/¥118.51 billion). Almost half of the CCE (45.62%/¥112.64 billion) was consumed by patients aged 60 or above. Adolescent patients up to an age of 14 (including those aged 14) mainly chose secondary or tertiary hospitals for treatment. Chronic non-communicable diseases accounted for the largest share of CCE consumption, with circulatory diseases accounting for the highest proportion. CONCLUSIONS: This study identified significant differences in CCE consumption in Beijing according to region, gender, age, and disease. Currently, the utilization of resources in medical institutions is not reasonable, and the hierarchical medical system is not sufficiently effective. Therefore, the government needs to optimize the allocation of resources according to the needs of different groups and rationalize the institutional process and functions.

Enhancing the Stability and Bioaccessibility of Tree Peony Seed Oil Using Layer-by-Layer Self-Assembling Bilayer Emulsions.

Tree peony seed oil (TPSO) is an important plant source of n-3 polyunsaturated fatty acid (α-linolenic acid, ALA > 40%) that is receiving increasing attention for its excellent antioxidant and other activities. However, it has poor stability and bioavailability. In this study, a bilayer emulsion of TPSO was successfully prepared using a layer-by-layer self-assembly technique. Among the proteins and polysaccharides examined, whey protein isolate (WPI) and sodium alginate (SA) were found to be the most suitable wall materials. The prepared bilayer emulsion contained 5% TPSO, 0.45% whey protein isolate (WPI) and 0.5% sodium alginate (SA) under selected conditions and its zeta potential, droplet size, and polydispersity index were -31 mV, 1291 nm, and 27%, respectively. The loading capacity and encapsulation efficiency for TPSO were up to 84% and 90.2%, respectively. It was noteworthy that the bilayer emulsion showed significantly enhanced oxidative stability (peroxide value, thiobarbituric acid reactive substances content) compared to the monolayer emulsion, which was accompanied by a more ordered spatial structure caused by the electrostatic interaction of the WPI with the SA. This bilayer emulsion also exhibited markedly improved environmental stability (pH, metal ion), rheological properties, and physical stability during storage. Furthermore, the bilayer emulsion was more easily digested and absorbed, and had higher fatty acid release rate and ALA bioaccessibility than TPSO alone and the physical mixtures. These results suggest that bilayer emulsion containing WPI and SA is an effective TPSO encapsulation system and has significant potential for future functional food development.

Forecasting regional short-term freight volume using QPSO-LSTM algorithm from the perspective of the importance of spatial information.

It is of great significance to accurately and efficiently predict expressway freight volume to improving the supervision level of the transportation industry and reflect the performance of transportation. Using expressway toll system records to predict regional freight volume plays an important role in the development of expressway freight organization work; especially, the short-term (hour, daily or monthly) freight volume is directly related to the compilation of regional transportation plans. Artificial neural networks have been widely used in forecasting in various fields because of their unique structural characteristics and strong learning ability, among which the long short-term memory (LSTM) network is suitable for processing and predicting series with time interval attributes such as expressway freight volume data. Considering the factors affecting regional freight volume, the data set was reconstructed from the perspective of spatial importance; we then use a quantum particle swarm optimization (QPSO) algorithm to tune parameters for a conventional LSTM model. In order to verify the efficiency and practicability, we first selected the expressway toll collection system data of Jilin Province from January 2018 to June 2021, and then used database and statistical knowledge to construct the LSTM data set. In the end, we used a QPSO-LSTM algorithm to predict the freight volume at the future times (hour, daily or monthly). Compared with the conventional LSTM model without tuning, the results of four randomly selected grids naming Changchun City, Jilin city, Siping City and Nong'an County show that the QPSO-LSTM network model based on spatial importance has a better effect.

Association of plasma lipid metabolism profiles with overall survival for patients with gastric cancer undergoing gastrectomy based on 1H-NMR spectroscopy.

BACKGROUND: Lipid metabolism dysregulation is a prominent metabolic alteration in various cancers. The study aimed to explore the association of plasma lipid metabolism profiles with overall survival (OS) for gastric cancer (GC) patients who received gastrectomy. METHODS: GC patients who were treated with gastrectomy and measured with plasma lipid metabolism profiles using proton nuclear magnetic resonance (1H-NMR) spectroscopy in Nanfang Hospital between January 1, 2017, and October 31, 2018, were recruited. The Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to analyze variables selected by univariate analysis for OS. An index of plasma lipid metabolism profiles, named plasma lipid metabolism index (PLMI), was constructed by variables' coefficients in LASSO regression to explore its association with OS and its role in the prediction model. RESULTS: A total of 158 GC patients were included in this study. Four of the 110 lipid profiles, including LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, were selected to construct the PLMI. The optimal cut-off value of PLMI for OS was used to classify the population into two subgroups, the high PLMI group (≥ - 0.163) and the low PLMI group (< - 0.163). The high PLMI group had a shorter OS (p = 0.0034) and was the independent risk factor for OS (Hazard Ratio = 2.13, 95% Confidence Interval (CI): 1.07-4.22, p = 0.031) after adjusting for perineural invasion and tumor stage. In subsets of the I-III stage and treating postoperative chemotherapy, high PLMI also had an unfavorable correlation with OS (p = 0.016 and p = 0.0086, respectively). The nomogram prediction models of both the training cohort and validation cohort showed good calibration and discrimination with the concordance indexes of 0.806 (95% CI, 0.732-0.880) in the training cohort and 0.794 (95% CI, 0.725-0.862) in the validation cohort. CONCLUSIONS: This study found that the index derived from the LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, was significantly associated with overall survival, suggesting that regulating lipid metabolisms might improve the prognosis for GC patients.

A dandelion-like nanomedicine via hierarchical self-assembly for synergistic chemotherapy and photo-dynamic cancer therapy.

The synergistic effect of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like nanomedicine (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic ß-cyclodextrins (ß-CD) doped lipid-based vesicles as the core (receptacle) and ß-CD modified camptothecin (CPT) pro-drug as the flyable dandelion seeds. The ß-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular ß-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the internalization into cancer cells. CPT interacted with ß-CD through glutathione (GSH)-cleavable disulfide bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.