Dual Recognition Strategy-Based Ratiometric Electrochemical Assay for Ultrasensitive and Accurate Detection of Specific Circulating Tumor Cells.

Sensitive, specific, and accurate detection of circulating tumor cells (CTCs) is of great importance in the diagnosis and prognosis of cancer. Herein, an ultrasensitive ratiometric electrochemical biosensor was designed with a dual recognition strategy for highly specific and accurate detection of circulating MCF-7 human breast cancer cells based on gold film-modified porous organic cages loaded with ferrocene (Au/Fc@POCs) as the substrate and methylene blue-encapsulated covalent organic frameworks (MB@COFs) as the label material, producing two independent electrochemical signals from the Fc and MB probes, respectively. As the concentration of MCF-7 cells increases, the electrochemical signal of MB enhances significantly while the oxidation signal of Fc decreases remarkably. Under optimal experimental conditions, the ratios (IMB/IFc) between the double signals showed a broad dynamic range of 10 to 1 × 107 cells/mL with an effectively lower detection limit of 1 cells/mL (S/N = 3). Furthermore, the biosensor was able to accurately enumerate MCF-7 cells in human serum samples with excellent results. In this work, the developed ratiometric electrochemical biosensor offers a reliable and sensitive strategy for the quantitative determination of circulating MCF-7 human breast cancer cells as well as an effective approach for the clinical detection of rare cancer cells, especially in early stage cancer diagnosis.

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

A broadly protective antibody targeting glycoprotein Gn inhibits severe fever with thrombocytopenia syndrome virus infection.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.

Interleukin-4-Loaded Heparin Hydrogel Regulates Macrophage Polarization to Promote Osteogenic Differentiation.

In bone tissue engineering, biological scaffolds are designed with structural and functional properties that closely resemble the extracellular environment, aiming to establish a microenvironment conducive to osteogenesis. Macrophages hold significant potential for promoting osteogenesis and modulating the biological behavior of tumor cells. Multiple coculture experiments of macrophages and osteoblasts have demonstrated that macrophage polarization significantly impacts osteogenesis. Therefore, exploring bone biomaterials that can modulate macrophage polarization holds great clinical significance. In this study, heparin was modified with maleimide and was used as a raw material to form a hydrogel with 4-am-PEG-SH. The compound was used to polarize macrophages and promote osteogenesis after combining with interleukin 4 (IL-4) by taking advantage of the electronegativity of heparin. The results revealed overexpressed M2 macrophage-related phenotypic genes and cocultivation with MC3T3-E1 cells demonstrated the osteogenesis-promoting effect of the loaded IL-4 heparin hydrogel. Previous research reported that hydrogel loaded with IL-4 can be used as a biomaterial for osteogenesis promotion. Heparin materials used in this paper are derived from clinically anticoagulant drugs and feature a simple operation. The synthesized hydrogel effectively binds cytokines, regulates macrophages to induce osteogenesis and has many potential clinical applications.

Development of a marital self-disclosure programme for alleviating the fear of cancer recurrence in patients with gastric cancer and undergoing chemotherapy: a modified Delphi method.

Aim: This study aimed to develop a marital self-disclosure programme to alleviate the fear of cancer recurrence in patients with gastric cancer who are undergoing chemotherapy. Design: Delphi method. Methods: Data from available literature and stakeholder interviews were utilised to formulate the initial draft of a marital self-disclosure programme aimed to alleviate the fear of cancer recurring in patients with gastric cancer and undergoing chemotherapy. A panel of experts subsequently conducted a two-round modified Delphi method to finalise the programme. Results: A total of 13 experts participated in the first round of consultation, while 11 experts were involved in the second round, as two experts withdrew due to unavailability. The response rates of both rounds of expert consultation were 100 and 84.62%, respectively, and the expert authority coefficients (Cr) of the programme were 0.83 and 0.84, respectively. The coordination coefficients of the expert opinions were 0.124 (χ2 = 61.214, p = 0.010) and 0.167 (χ2 = 69.668, p = 0.001) for each Delphi round. The average score of the second round was (4.545 ± 0.688) to (5.000 ± 0), with a full score ratio of 0.55-1.00. The coefficient of variation (CV) ranged from 0 to 0.031. Outcomes from both rounds of consultations were considered acceptable and credible. The finalised marital self-disclosure programme for alleviating the fear of cancer recurrence in patients with gastric cancer undergoing chemotherapy consists of two parts; disclosure guidance for patients and their spouse with nine items, and the structure and themes of marital self-disclosure with 31 items. Patient or public contribution: After two rounds of expert consultations, the marital self-disclosure programme for patients with gastric cancer undergoing chemotherapy is suggested to be scientifically valid and reliable. This programme is anticipated to potentially support patients and their spouses effectively by providing a reliable intervention plan focused on alleviating the fear of cancer recurrence.

Novel diacylglycerol oil-based nanostructured lipid carriers improves the stability and digestibility of lycopene.

Diacylglycerol (DAG) has garnered attention for its safe and nutritious qualities, and its utilization in emulsion systems to encapsulate hydrophobic bioactives is anticipated to enhance their bioaccessibility. Thus, this study aimed to evaluate the influence of DAG oil as a carrier on the stability and digestive characteristics of nanostructured lipid carriers (NLCs) containing lycopene (LYC). The results indicated that DAG oil demonstrated superior storage and heating stability in comparison to triacylglycerol (TAG) oil. Furthermore, NLCs formulated with DAG oil exhibited a faster rate of lipolysis (>76.3%) and higher loading capacity (1.48%), resulting in an approximate 11% enhancement in the bioaccessibility of LYC (reaching up to 31.4%). DAG oils show considerable potential for enhancing and prolonging the properties and bioactivity of NLC carriers, thereby boosting bioaccessibility. The incorporation of DAG oil in food systems holds promise for enriching their functionality over traditional TAG oil.

Molecular and structural basis of an ATPase-nuclease dual-enzyme anti-phage defense complex.

Coupling distinct enzymatic effectors emerges as an efficient strategy for defense against phage infection in bacterial immune responses, such as the widely studied nuclease and cyclase activities in the type III CRISPR-Cas system. However, concerted enzymatic activities in other bacterial defense systems are poorly understood. Here, we biochemically and structurally characterize a two-component defense system DUF4297-HerA, demonstrating that DUF4297-HerA confers resistance against phage infection by cooperatively cleaving dsDNA and hydrolyzing ATP. DUF4297 alone forms a dimer, and HerA alone exists as a nonplanar split spiral hexamer, both of which exhibit extremely low enzymatic activity. Interestingly, DUF4297 and HerA assemble into an approximately 1 MDa supramolecular complex, where two layers of DUF4297 (6 DUF4297 molecules per layer) linked via inter-layer dimerization of neighboring DUF4297 molecules are stacked on top of the HerA hexamer. Importantly, the complex assembly promotes dimerization of DUF4297 molecules in the upper layer and enables a transition of HerA from a nonplanar hexamer to a planar hexamer, thus activating their respective enzymatic activities to abrogate phage infection. Together, our findings not only characterize a novel dual-enzyme anti-phage defense system, but also reveal a unique activation mechanism by cooperative complex assembly in bacterial immunity.

Effects of modified-BHI medium on the growth and metabolites of Akkermansia muciniphila.

Akkermansia muciniphila (Akk) has recently become popular due to its therapeutic effect on various diseases. However, Akk's high-density cultivation is difficult due to its anaerobic characteristics. Therefore, Akk was cultured with modified brain-heart infusion (M-BHI) to reach 1011 CFU/mL. 1H-NMR determined the metabolites of Akk and validated them by an amino acid analyzer. Compared to the BHI, Akk significantly up-regulated lactate, histidine, fumaric acid, cytidine, threonine, arginine, and hydroxyproline in the M-BHI and significantly down-regulated methionine, trimethylamine, and sarcosine. Regarding pathway enrichment analysis, histidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism mainly regulate differential metabolites. In addition, M-BHI alters the metabolic profile by affecting Akk's involvement in amino acid metabolism remodeling. Changed metabolites showed that Akk fermentation in M-BHI may play a physiological role in regulating immune homeostasis and reducing risk factors related to diseases. Therefore, M-BHI provides a promising reference for Akk cultivation in future industrial preparation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01492-x.

Marital Self-Disclosure Intervention for the Fear of Cancer Recurrence in Chinese Patients With Gastric Cancer: Protocol for a Quasiexperimental Study.

BACKGROUND: Patients with gastric cancer experience different degrees of fear of cancer recurrence. The fear of cancer recurrence can cause and worsen many physical and psychological problems. We considered the "intimacy and relationship processes in couples' psychosocial adaptation" model. OBJECTIVE: The study aims to examine the effectiveness of a marital self-disclosure intervention for improving the level of fear of cancer recurrence and the dyadic coping ability among gastric cancer survivors and their spouses. METHODS: This is a quasiexperimental study with a nonequivalent (pretest-posttest) control group design. The study will be conducted at 2 tertiary hospitals in Taizhou City, Jiangsu Province, China. A total of 42 patients with gastric cancer undergoing chemotherapy and their spouses will be recruited from each hospital. Participants from Jingjiang People's Hospital will be assigned to an experimental group, while participants from Taizhou People's Hospital will be assigned to a control group. The participants in the experimental group will be involved in 4 phases of the marital self-disclosure (different topics, face-to-face) intervention. Patients will be evaluated at baseline after a diagnosis of gastric cancer and reassessed 2 to 4 months after baseline. The primary outcome is the score of the Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for patients. The secondary outcomes are the scores of the FoP-Q-SF for partners and the Dyadic Coping Inventory. RESULTS: Research activities began in October 2022. Participant enrollment and data collection began in February 2023 and are expected to be completed in 12 months. The primary results of this study are anticipated to be announced in June 2024. CONCLUSIONS: This study aims to assess a marital self-disclosure intervention for improving the fear of cancer recurrence in Chinese patients with gastric cancer and their spouses. The study is likely to yield desirable positive outcomes as marital self-disclosure is formulated based on evidence and inputs obtained through stakeholder interviews and expert consultation. The study process will be carried out by nurses who have received psychological training, and the quality of the intervention will be strictly controlled. TRIAL REGISTRATION: ClinicalTrials.gov NCT05606549; https://clinicaltrials.gov/study/NCT05606549. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55102.

Distance-specific functional connectivity strength alterations in human immunodeficiency virus asymptomatic neurocognitive impairment patients: a cross-sectional study.

Background: Asymptomatic neurocognitive impairment (ANI) is the mildest form of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs), and functional connectivity strength (FCS) alternations have been observed in the ANI stage. However, it is not clear whether the FCS alterations are influenced by the anatomical distance. This study sought to investigate distance-specific FCS changes in HIV ANI patients. Methods: In total, 29 patients with HAND and 32 healthy controls (HCs) were enrolled in the study. Between-group differences were detected for short, middle and long range anatomical distance FCS. A correlation analysis was performed to examine the relationship between distance-specific FCS and immunological parameters and neuropsychological tests. A receiver operating characteristic (ROC) analysis was conducted to examine the discriminative performance for HIV ANI patients. Results: In comparison to the HCs, the HAND patients showed increased short-range FCS in the left inferior parietal lobule (IPL), middle-range FCS in the superior temporal gyrus (STG), long-range FCS in the left precuneus (PCC), and decreased FCS in the right postcentral gyrus (PCG) (cluster P<0.05, voxel significance P<0.001). Further, the long-range FCS in the right PCG was negatively correlated with the CD4/CD8 ratio (r=-0.479, 95% confidence interval (CI): -0.735 to -0.104, P=0.015), and the distance-specific FCS also showed good classification performance between the HAND patients and HCs. The left IPL, left STG, right PCG, and left PCC had areas under the curve (AUCs) of 0.875 [95% confidence interval (CI): 0.758-0.949, P<0.0001], 0.806 (95% CI: 0.677-0.900, P<0.0001), 0.855 (95% CI: 0.734-0.935, P<0.0001), and 0.852 (95% CI: 0.754-0.950, P<0.0001), respectively. There was no significant relationship between the distance-specific FCS and the neuropsychological tests. Conclusions: Distance-specific FCS could be used to examine subtle alternations in HIV-infected patients in the ANI stage and help to explain the possible neurophysiological mechanism of HAND.

Trimethylamine N-oxide promotes oxidative stress and lipid accumulation in macrophage foam cells via the Nrf2/ABCA1 pathway.

Recently, trimethylamine N-oxide (TMAO) has been considered a risk factor for cardiovascular disease and has a proatherogenic effect. Many studies have found that TMAO is involved in plaque oxidative stress and lipid metabolism, but the specific mechanism is still unclear. In our study, meta-analysis and bioinformatic analysis were firstly conducted in the database, and found that the effect of high plasma TMAO levels on promoting atherosclerotic plaque may be related to the expression of key antioxidant genes nuclear factor erytheroid-derived-2-like 2 (NFE2L2/Nrf2) decreased. Next, we assessed the role of Nrf2-mediated signaling pathway in TMAO-treated foam cells. Our results showed that TMAO can inhibit the expression of Nrf2 and its downstream antioxidant response element such as heme oxygenase-1 (HO-1) and glutathione peroxidase4 (GPX4), resulting in increased production of reactive oxygen species and decreased activity of superoxide dismutase, promoting oxidative stress. And TMAO can also promote lipid accumulation in foam cells by inhibiting cholesterol efflux protein expression. In addition, upregulation of Nrf2 expression partially rescues TMAO-induced oxidative stress and reduces ATP-binding cassette A1 (ABCA1)-mediated lipid accumulation. Therefore, TMAO promotes oxidative stress and lipid accumulation in macrophage foam cells through the Nrf2/ABCA1 pathway, which may provide a potential mechanism for the proatherogenic effect of TMAO.

Effects of combined exposure to polystyrene microplastics and 17α-Methyltestosterone on the reproductive system of zebrafish.

Polystyrene microplastics (PS-MPs) are important carriers of pollutants in water. 17α-Methyltestosterone (MT) is a synthetic environmental endocrine disrupting chemical (EDC) with androgenic effects. To study the effects of PS-MPs and MT on zebrafish reproductive systems, zebrafish were exposed to 0 or 50 ng L-1 MT, 0.5 mg∙L-1 PS-MPs, or 50 ng∙L-1 MT + 0.5 mg∙L-1 PS-MPs for 21 d. The results showed that the different exposure reagents caused varying degrees of damage to the reproductive systems in zebrafish, with the extent of damage increasing as the exposure duration increased. Histological analysis of the gonads revealed that the ratio of mature oocytes and mature spermatozoa in the gonad decreased gradually with increased exposure time, with the ratio being Control > PS-MPs > MT > MT + PS-MPs in decreasing order. The results of quantitative real-time PCR (qRT‒PCR) showed that in female fish treated for 7 d, the expression of cyp11a mRNA was significantly reduced in all three treatment groups(MT, PS-MPs, and MT + PS-MPs), while in the group treated for 14 d with MT + PS-MPs, the expression of cyp19a1a and StAR mRNA was significantly increased. In male fish exposed for 21 d, the expression of cyp11a, cyp17a1, cyp19a1a, StAR, 3ß-HSD, and 17ß-HSD3 mRNA was significantly decreased in MT + PS-MPs. ELISA results showed that after 14 d of exposure, the levels of E2, LH, and FSH in the ovaries of female fish were significantly reduced in all three treatment groups. Similarly, the levels of T, E2, LH, and FSH in the testis of male fish were significantly reduced after 14 d of exposure to PS-MPs and MT + PS-MPs. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. The cross-generational toxicity of PS-MPs themselves may be negligible, but it can exacerbate the toxicity of MT, making the cross-generational effects more pronounced in the offspring, causing offspring mortality and malformations. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. In addition, MT caused malformations such as pericardial edema, yolk cysts, and spinal deformities in zebrafish during the incubation period.

Controlling Risk Factors Reduces Cancer Risk in Patients with Atherosclerotic Cardiovascular Disease: A Cohort Study.

BACKGROUND: The association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. METHODS: A total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. RESULTS: A total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. CONCLUSIONS: Cancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.

E3 ubiquitin ligase RNF180 impairs IPO4/SOX2 complex stability and inhibits SOX2-mediated malignancy in ovarian cancer.

RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV. Here, we explored the potential signaling pathways related to RNF180 and IPO4. It was first verified that RNF180 is downregulated and IPO4 is upregulated in OV. By overexpressing or knocking down RNF180 in OV cells, we confirmed that RNF180 inhibited the malignant behaviors of OV cells both in vitro and in vivo. Bioinformatics analysis and proteomics experiments found that RNF180 could interact with IPO4 and promote the degradation of IPO4 through ubiquitination. In addition, overexpression of IPO4 removed the inhibitory effect of RNF180 on OV. We subsequently found that IPO4 could bind to the oncogene Sex determining Region Y-box 2 (SOX2). Knockdown of IPO4 in OV cells decreased SOX2 protein level in nucleus and promoted cyclin-dependent kinase inhibitory protein-1 (p21) expression. Overexpression of RNF180 also inhibited the expression of SOX2 in nucleus. All these results indicated that RNF180 inhibited the nuclear translocation of SOX2 by promoting ubiquitination of IPO4, which ultimately promoted the expression of p21 and then suppressed the progression of OV. This study verified the tumor suppressor effect of RNF180 on OV, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in OV and identified for OV.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

BACKGROUND: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. METHODS: 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. RESULTS: The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. CONCLUSIONS: PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.

Experience of management of pediatric upper gastrointestinal perforations: a series of 30 cases.

Background: This study aimed to explore the characteristics of pediatric upper gastrointestinal (UGI) perforations, focusing on their diagnosis and management. Methods: Between January 2013 and December 2021, 30 children with confirmed UGI perforations were enrolled, and their clinical data were analyzed. Two groups were compared according to management options, including open surgical repair (OSR) and laparoscopic/gastroscopic repair (LR). Results: A total of 30 patients with a median age of 36.0 months (1 day-17 years) were included in the study. There were 19 and 11 patients in the LR and OSR groups, respectively. In the LR group, two patients were treated via exploratory laparoscopy and OSR, and the other patients were managed via gastroscopic repair. Ten and three patients presented the duration from symptom onset to diagnosis within 24 h (p = 0.177) and the number of patients with hemodynamically unstable perforations was 4 and 3 in the LR and OSR groups, respectively. Simple suture or clip closure was performed in 27 patients, and laparoscopically pedicled omental patch repair was performed in two patients. There was no significant difference in operative time and length of hospital stay between the LR and OSR groups. Treatment failed in two patients because of severe sepsis and multiple organ dysfunction syndrome, including one with fungal peritonitis. Conclusion: Surgery for pediatric UGI perforations should be selected according to the general status of the patient, age of the patient, duration from symptom onset, inflammation, and perforation site and size. Antibiotic administration and surgical closure remain the main strategies for pediatric UGI perforations.

Zn-Induced Synthesis of Porous Fe-N,S-C Electrocatalyst with Iron-Based Active Sites Containing Sulfides, Oxides and Nitrides for Efficient Oxygen Reduction and Zinc-Air Batteries.

There is an urgent need to design and synthesize non-noble metal electrocatalysts (NNMEs) for the replacement of platinum-based electrocatalysts to enhance the sluggish oxygen reduction reaction (ORR) for Zn-air batteries and fuel cells. Herein, Fe-N,S-C materials were fabricated through two steps: first, reprecipitating hemin by adjusting the pH and, then, decorating it with melamine and cysteine in the presence of Zn2+. The resulting Fe-N,S-C-950 (Zn) was prepared after pyrolysis at 950 °C. Using this method, abundant iron-based active species with good dispersion were obtained. The fabrication of more micropores in Fe-N,S-C-950 (Zn) plays a positive role in the improvement of ORR activity. On comparison, Fe-N,S-C-950 (Zn) outperforms Fe-N,S-C-950 and Fe-N-C-950 (Zn) with respect to the ORR due to its larger specific surface area, porous structure, multiple iron-based active sites and N- and S-doped C. Fe-N,S-C-950 (Zn) achieves outstanding ORR performances, including a half-wave potential (E1/2) of 0.844 V and 0.715 V versus a reversible hydrogen electrode (RHE) in 0.1 M KOH and 0.1 M HClO4 solution, respectively. In addition, Fe-N,S-C-950 (Zn) shows an outstanding Zn-air battery performance with an open-circuit voltage (OCV) of 1.450 V and a peak power density of 121.9 mW cm-2, which is higher than that of 20 wt% Pt/C. As a result, the as-prepared electrocatalyst in this work shows the development of the Zn-assisted strategy combined with the assembly of porphyrins as NNMEs for the enhancement of the ORR in both alkaline and acidic solutions.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

New Insights into Extracellular Vesicles between Adipocytes and Breast Cancer Orchestrating Tumor Progression.

In recent years, obesity has been widely considered an independent risk factor for diseases/disorders including inflammation, cardiovascular disease, and cancer. Adipocytes separate in diverse types of tissues, playing vital roles in not only homeostasis but also disease progression. Adipose tissue is not only an energy organ but is also an endocrine organ that can communicate with other cells in the microenvironment. In this review, we assess the functions of breast cancer-associated adipose tissue-derived extracellular vesicles (EVs) in the progression of breast cancer including proliferation, metastasis, drug resistance, and immune regulation. A better understanding of the role of EVs in the crosstalk between adipocytes and breast cancer will provide an understanding of the cancer biology and progression, which would further drive improvements of diagnostic strategies as well as therapeutic insights.