Search

Abstract Background Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. Methods We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. Results We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. Conclusions We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

There has been an emergence of a diversity of microalgal mixotrophic synergistic mechanisms due to substrate differences. In this study, the effects of the mixotrophic culture of Chlorella vulgaris were examined. The maximum values of cell density, specific growth rate, and cell dry weight of Chlorella vulgaris were 3.52*107 cells/mL, 0.75 d−1, and 3.48 g/L in the mixotrophic mode, respectively. These were higher than the corresponding values of photoautotrophic or heterotrophic modes. Moreover, it was found that the concentrations of sodium bicarbonate consumed by the Chlorella vulgaris under mixotrophic and photoautotrophic modes were 635 mg/L/d and 505 mg/L/d, respectively; the concentrations of sodium acetate consumed by the Chlorella vulgaris under mixotrophic and heterotrophic modes were 614 mg/L/d and 645 mg/L/d, respectively. The activity of Rubisco was 9.36 U/mL in the mixotrophic culture, which was 3.09 and 4.85 times higher than that of the photoautotrophic and heterotrophic modes, respectively. This indicated that the differences for the carbon source absorption efficiency of Chlorella vulgaris in the mixotrophy led to different internal metabolic efficiencies when compared to photoautotroph or heterotrophy. Additionally, Chlorella vulgaris exhibits a more rapid energy metabolism efficiency when operating in the mixotrophic mode.

Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury. In this study, a Sprague-Dawley (SD) rat model of As-poisoned was established, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen. After feeding the rats with As diet (50 mg/kg) for 90 days, the spleen tissue of the rats in the As-poisoned group was damaged, the level of As was significantly higher than that of the control group (P < 0.001), and the level of inflammatory cytokine interleukin-6 (IL-6) was decreased (P < 0.01). Proteomics and metabolomics results showed that a total of 134 differentially expressed proteins (DEPs) (P < 0.05 and fold change > 1.2) and 182 differentially expressed metabolites (DEMs) (VIP >1 and P < 0.05) were identified in the spleens of the As poisoned group compared to the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cell mediated cytotoxicity, and ribosomes. The major pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. The integrated analysis of these two omics suggested that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure. The results indicate that As exposure can cause spleen damage in rats. Through proteomic and metabolomic analysis, the key proteins and metabolites and their associated mechanisms were obtained, which provided a basis for further understanding of the molecular mechanism of spleen immune damage caused by As exposure.

Objectives: To synthesize the clinical experience of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) or pulmonary fibrosis (PF) receiving lung transplantation (LTx) and compare the characteristics and outcomes of COVID-19 and non-COVID-19 LTx patients. Methods: A literature search of online databases (PubMed, Web of Science, Embase, the Cochrane Library, China Science and Technology Journal Database, and Wan Fang databases) was performed regarding LTx for COVID-19–associated ARDS or PF. This study was registered on PROSPERO (CRD2024507647). Results: Eight eligible studies were included with 478 COVID-19 LTx patients and 163 non-COVID-19 LTx patients. In COVID-19 LTx patients, the pooled hospital mortality and follow-up survival rate was 0.00% (95% CI 0.00-0.03) and 87.40% (95% CI 0.76-0.96). Compared to non-COVID-19 LTx patients, COVID-19 LTx patients were associated with significantly higher rate of primary graft dysfunction (odds ratio [OR] 8.72, 95% CI 3.54-21.47, P < 0.001) but significantly higher follow-up survival rate (OR 2.48, 95% CI 1.02-6.01, P = 0.04), within an overall similar follow-up period. Conclusions: For patients with COVID-19–associated ARDS or PF, LTx offers acceptable short-term outcomes and is suggested as a viable lifesaving treatment.

In situ phase separation precipitates play an important role in enhancing the thermoelectric properties of copper sulfides by suppressing phonon transmission. In this study, Cu1.8S composites were fabricated by melting reactions and spark plasma sintering. The complex structures, namely, micron-PbS, Sb2S3, nano-FeS, and multiscale pores, originate from the introduction of FePb4Sb6S14 into the Cu1.8S matrix. Using effective element (Fe) doping and multiscale precipitates, the Cu1.8S+0.5 wt% FePb4Sb6S14 bulk composite reached a high dimensionless figure of merit (ZT) value of 1.1 at 773 K. Furthermore, the modulus obtained for this sample was approximately 40.27 GPa, which was higher than that of the pristine sample. This study provides a novel strategy for realizing heterovalent doping while forming various precipitates via in situ phase separation by natural minerals, which has been proven to be effective in improving the thermoelectric and mechanical performance of copper sulfides and is worth promoting in other thermoelectric systems.

Abstract As the largest microecosystem in the human body, gut microbes (GMs) and their metabolites play an important role in regulating human health. In recent years, immune checkpoint therapy (ICT) combined with antiangiogenic agents is an emerging combination therapy for cancer. There is growing evidence that GMs can affect the effectiveness of drugs to treat cancer. GMs not only regulate angiogenesis in the tumor microenvironment, but also influence the efficacy of immune checkpoint inhibitors. Many studies show that Bifidobacterium can upregulate the anticancer function of immune checkpoint blockers. In addition, GMs have been found to be involved in the formation of blood vessels and other developmental processes. Clinically, GMs are believed to play a key role in patients receiving antiangiogenic therapy and ICT. In this perspective, we provide an overview of the composition and function of the gut microbiome, and discuss the role of the GMs against the conditioning of angiogenic therapy and ICT. We also summarize new approaches and clinical translational trials using GMs for cancer therapy, and present opportunities and challenges for targeting GMs for cancer therapy in the future.

BackgroundHigh mobility group box 1 (HMGB1) and indoleamino-2, 3-dioxygenase (IDO) participate in the occurrence and development of esophageal squamous cell carcinoma (ESCC), regulate the tumor immune microenvironment, and are closely related to tumor growth and metastasis. However, the regulatory mechanism of serum HMGB1 and IDO has not been clarified and needs further exploration.MethodsBlood samples of 55 ESCC patients initially hospitalized in the Fourth Hospital of Hebei Medical University from August 2021 to January 2022 were selected as the ESCC group, and relevant clinical data were collected, and blood samples from 40 healthy people during the same period were selected as the control group. Serum HMGB1 and IDO levels were determined by ELISA, and lymphocyte subsets in peripheral blood of all subjects were detected by flow cytometry. The correlation between the expression levels of HMGB1 and IDO in ESCC cells was detected by Western blot.ResultsSerum HMGB1 and IDO levels were significantly increased in ESCC patients, and with the progression of ESCC patients, serum HMGB1 and IDO levels were also gradually increased; serum HMGB1 was significantly correlated with IDO; serum HMGB1 and IDO combined with CEA and SCC-Ag were of high value in predicting the clinical progression of ESCC patients; the absolute counts of CD4+CD28+T cells and CD8+CD28+T cells in high HMGB1 group were significantly lower than those in low HMGB1 group, while the percentage of CD4+PD-1+T cells was significantly higher than that in low HMGB1 group; the percentage and absolute counts of CD4+CD28+T cells and the absolute counts of CD8+CD28+T cells in high IDO group were significantly lower than those in the low IDO group, while the percentage of CD8+PD-1+T cells was significantly higher than that in the low IDO group; increased serum HMGB1 and IDO expression levels were closely related to poor prognosis in ESCC patients; and HMGB1 may promote IDO expression by activating NF-κB signaling pathway.ConclusionSerum HMGB1 and IDO have a synergistic effect, they inhibit immune function and promote tumor progression in ESCC patients, and also lead to poor prognosis.

Background: Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). Objectives: To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. Design: A multicenter, open-label, phase Ib trial. Methods: Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1–2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3–5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. Results: A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%–93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%–87.5% for lower doses; grade 4, 46.7% and 4.2%–20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%–54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5–82.6) and patients progressing after ET (53.3%; 95% CI 26.6–78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9–46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9–24.1) with fulvestrant. Conclusion: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration: ClinicalTrials.gov identifier: NCT03481998.

Brain metastases (BM) represent a common and severe complication of breast cancer (BC), emerging in approximately 10%–16% of all BC patients. The prevalent approach for treating BC patients with BM encompasses a multimodal strategy, combining surgery, whole brain radiation therapy, and stereotactic radiosurgery. Yet, a concrete guideline for localized treatment strategies remains elusive, while systemic treatments like small-molecule-targeted therapy and immunotherapy are still in the clinical trial phase. This case study presents a significant clinical response to anlotinib treatment in a patient with estrogen receptor-negative, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, complicated by BM. After the standard first-line treatment including albumin-bound paclitaxel, trastuzumab and pertuzumab, and a second-line treatment involving pyrotinib, capecitabine, and radiotherapy did not produce the desired results, the patient was then administered anlotinib in combination with pyrotinib and letrozole as a third-line treatment, which led to a partial response (PR). The findings suggest that anti-angiogenic therapy, specifically anlotinib, could be regarded as a promising therapeutic option for BC patients with BM.

Abstract Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

Abstract Background The combination of dual‐targeted human epidermal growth factor receptor 2 (HER2) therapy and chemotherapy is the standard first‐line regimen for recurrent/metastatic breast cancer (mBC). However, the toxicity of such combination therapy can lead to some patients being unable to tolerate adverse events or bear treatment costs. As a novel irreversible pan‐ErbB receptor TKI (pyrotinib), can the dual oral administration of pyrotinib plus capetabine (PyroC) provide first‐line survival benefits and serve as a more affordable treatment option? Methods This real‐world retrospective study included patients diagnosed with HER2‐positive mBC who received PyroC as a first‐line treatment at West China Hospital between May 2018 and July 2023. The survival data and toxicity profiles were reported in this study. Results A total of 64 patients received PyroC as first‐line therapy. The median progression‐free survival (PFS) was 19.6 months (95% CI 15.0–27.2), while overall survival (OS) has not yet been reached. Kaplan–Meier analysis indicated that age (≥60, p = 0.03) and metastasis sites (p = 0.004) were related to poor efficacy of PyroC, while there was no relationship between effectiveness and menstrual status, hormone receptor (HR) status or previous treatment with anti‐HER2 therapy. Furthermore, the objective response rate (ORR) and disease control rate (DCR) were 79.7% and 98.4%, respectively. Of the patients, 78.1% reported treatment‐related adverse events (TRAEs). The predominant adverse events were diarrhea (n = 46, 71.9%) and hand‐foot syndrome (n = 10, 15.6%). Conclusion The dual oral administration regimen (PyroC) has a promising ORR or PFS in HER2‐positive mBC patients, with an acceptable safety profile and convenience.

Frequent oil spill accidents caused by transportation, storage and usage may lead to severe damage on aquatic and ecological environments. Effective methods for rapid oil recovery are urgently in demand. Polyvinyl chloride, hydrophobic nano-SiO2, expanded graphite were separately applied to polyurethane and melamine sponge to fabricate superhydrophobic sponge material. The selected superhydrophobic sponge was introduced to establish sponge - covered disc skimmer. Oil recovery tests of the device were conducted to determine the optimum parameters. The examined operating conditions encompassed sponge thickness, immersion depth, rotational speed, oil slick thickness, operation time. The results showed that the melamine sponge modified by both polyvinyl chloride and hydrophobic nano-SiO2 exhibits super-hydrophobicity with a water contact angle of 150.3°. The absorption capacity for diesel oil can reach 53.89 g/g. The absorption capacity can still achieve 90 % of its initial capacity even after 500 extrusion-absorption separation tests. The results indicate the superiority of the superhydrophobic sponge covered surface in oil recovery over the standard steel surface regardless of the operating conditions. The recovery rate of the device can still achieve 96.4 % of its initial capacity with 95 % efficiency even after 85 h operation. The results suggest the superhydrophobic sponge - covered disc skimmer may have great application perspectives in oil spill recovery.

Abstract Background This prospective real‐world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. Patients and Methods In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo−/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. Results One hundred and thirty‐four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3–15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first‐ or second‐line treatment was significantly better than those who received eribulin as ≥3‐line treatment (6.9 months [95% CI: 3.2–8.8] vs. 4.0 months [95% CI: 3.4–4.6], p = 0.006). The mPFS of patients with triple‐negative, HER2‐positive, and HER2(−)/HR(+) was 3.4 (95% CI: 2.7–4.1), 6.2 (95% CI: 2.3–10.1) and 5.0 months (95% CI: 4.1–5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6–6.3] vs. 4.0 months [95% CI: 3.3–4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non‐TNBC receiving eribulin as ≤2‐line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment‐related adverse events. Conclusion Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real‐world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

A horizontal towed linear coherent hydrophone array is often employed to estimate the spatial intensity distribution of incident plane waves scattered from the geological and biological features in an ocean acoustic waveguide using conventional beamforming. However, due to the physical limitations of the array aperture, the spatial resolution after conventional beamforming is often limited by the fat main lobe and the high sidelobes. Here, we propose a method originated from computer vision deblurring based on deep learning to enhance the spatial resolution of beamformed images. The effect of image blurring after conventional beamforming can be considered a convolution of beam pattern, which acts as a point spread function (PSF), and the original spatial intensity distributions of incident plane waves. A modified U-Net-like network is trained on a simulated dataset. The instantaneous acoustic complex amplitude is assumed following circular complex Gaussian random (CCGR) statistics. Both synthetic data and experimental data collected from the South China Sea Experiment in 2021 are used to illustrate the effectiveness of this approach, showing a maximum 700% reduction in a 3 dB width over conventional beamforming. A lower normalized mean square error (NMSE) is provided compared with other deconvolution-based algorithms, such as the Richardson–Lucy algorithm and the approximate likelihood model-based deconvolution algorithm. The method is applicable in various acoustic imaging applications that employ linear coherent hydrophone arrays with one-dimensional conventional beamforming, such as ocean acoustic waveguide remote sensing (OAWRS).

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi‐omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non‐targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high‐throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD.

Abstract Background Cancer therapy‐related cardiovascular toxicity (CTR‐CVT) is a major contributor to poor prognosis in breast cancer (BC) patients undergoing chemotherapy. Left ventricular global longitudinal strain (LV GLS) has predictive value for CTR‐CVT, while few researchers take into account late‐onset CTR‐CVT. This study sought to provide a guide for the prediction of late‐onset CTR‐CVT in primary BC over the 2 years follow‐up via strain and contrast‐enhanced echocardiography. Methods Anthracycline and anthracycline + targeted medication groups were created from 111 patients with stage I–III primary BC who were prospectively included. The left ventricular diastolic function, LV global long‐axis strain (GLS); left ventricular ejection fraction by contrast‐enhanced echocardiography (c‐LVEF), and electrocardiograms were collected at baseline, 3, 6, 12, and 24 months after the start of cancer treatment. The high‐sensitivity troponin‐T and NT‐pro BNP at baseline and 3 months after chemotherapy were measured. Results (1) LV GLS decreased in BC patients over time. (2) After 12 months' follow‐up, the LV GLS in the anthracycline+ targeted group was lower than in the anthracycline group. After 24 months' follow‐up, the GLS and c‐LVEF in the anthracycline + targeted group declined while the E/e’ increased. (3) Decreased LVEF (56%) and arrhythmia (38%) are the common causes of CTR‐CVT. Lower LVEF was a major factor in late‐onset CTR‐CVT. (4) Combination of LV GLS and c‐LVEF at 3 months were used as predictors for CTR‐CVT and exhibited a higher AUC than either one alone (AUC = 0.929, 95% CI: 0.863–0.970). LV GLS at 3 months can predict the late‐onset CTR‐CVT (AUC = 0.745, p

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28–75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30–9.11) and 3.72 (95% CI, 1.91–5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58–0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

ObjectiveTo explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death （YNSUD）, to provide the experimental basis for prevention and treatment of YNSUD.MethodsFour kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 （CCK-8）. The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase （LDH） Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.ResultsSpecies identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.ConclusionThe extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

As human progress forges ahead in the domain of ultra-low temperature advancements, conventional concrete materials have been inadequate in addressing the exigencies of practical engineering demands, Engineered Cementitious Composites (ECC), an emerging class of novel composite materials, whose investigation concerning performance under ultra-low temperature environments assumes profound significance. This paper employed Polyethylene (PE) fibers to fabricate Engineered Cementitious Composites (ECC) and investigated the impact of varying ultra-low temperature freezing-thawing cycles lower limit temperatures, as well as the number of freezing-thawing cycles, on the bending static load strength and bending fatigue properties of PE-ECC specimens. The results show that changes in lower limit temperatures and the number of freezing-thawing cycles have a substantial effect on the flexural static load strength of PE-ECC, the flexural strength and bending deflection of the specimens exhibit a notable decrease in values. Across various freezing-thawing conditions, the toughness value is consistently lower than that of the control group unaffected by freezing-thawing, thereby indicating a compromised energy absorption capacity of the matrix. The strength of the interfacial bonding between the fibers and the matrix is reduced, leading to a conspicuous increase in fiber pullout damage when the specimen fails. The fatigue life of PE-ECC subjected to freezing-thawing in ultra-low temperatures follows the two-parameter Weibull distribution, the fatigue life equations of PE-ECC under different freezing-thawing conditions with different probabilities of reliability are obtained by regression analysis. The results of this study can serve as a reference for analyzing the fatigue life of PE-ECC at ultra-low temperatures freezing-thawing cycles.

Abstract MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle‐derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR‐636, miR‐7641, miR‐28‐3p, and miR‐1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR‐636, miR‐7641, miR‐1246, and miR‐28‐3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs‐derived miR‐1246, miR‐28‐3p and total plasma miRNAs miR‐636, miR‐7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs‐derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.

Abstract Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti‐hypertensive. Using a meta‐analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002–2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was –1.42 (95% CI: –2.38, –0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: –1.28, –0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non‐significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi‐ethnic, large sample pool size, and a long period follow‐up study is still required to assert these claims.

Herein, we demonstrated that various activated carbons could be endowed with high ability activating peroxymonosulfate (PMS) just through pyrolysis for the degradation of various organic pollutants. The ofloxacin (OFX) was proved to be degraded rather than adsorbed in the advanced oxidation processes. The catalyst showed good stability and could be recovered by simple pyrolysis showing the initial activity. The defects were identified as active sites of the catalyst, and π-π∗ shake up was related to the catalyst activity. Mediated electron transfer was verified to be responsible for the degradation of OFX. The inhibition effect of furfuryl alcohol (FFA) on the degradation of contaminant was proved to be insufficient to verify 1O2. The main OFX degradation intermediates were identified by LC-MS, and possible degradation pathways were proposed. This study provided a simple way for the development of low-cost, metal-free, and high-efficient carbonaceous materials to activate PMS in advanced oxidation processes, and proposed new insights for the exploration of PMS activation mechanism.

We report multifrequency and multiepoch very long baseline interferometry studies of the subparsec jet in the Sombrero galaxy (M104, NGC 4594). Using Very Long Baseline Array data at 12, 22, 44, and 88 GHz, we study the kinematics of the jet and the properties of the compact core. The subparsec jet is clearly detected at 12 and 22 GHz, and the inner jet base is resolved down to ∼70 Schwarzschild radii ( R _s ) at 44 GHz. The proper motions of the jet are measured with apparent subrelativistic speeds of 0.20 ± 0.08 c and 0.05 ± 0.02 c for the approaching and the receding jet, respectively. Based on the apparent speed and jet-to-counterjet brightness ratio, we estimate the jet viewing angle to be larger than ∼37°, and the intrinsic speed to be between ∼0.10 c and 0.40 c . Their joint probability distribution suggests the most probable values of the viewing angle and intrinsic speed to be ${66^\circ }_{-6^\circ }^{+4^\circ }$ and 0.19 ± 0.04 c , respectively. We also find that the measured brightness temperatures of the core at 12, 22, and 44 GHz are close to the equipartition brightness temperature, indicating that the energy density of the radiating particles is comparable to the energy density of the magnetic field in the subparsec jet region. Interestingly, the measured core size at 88 GHz (∼25 ± 5 R _s ) deviates from the expected frequency dependence seen at lower frequencies. This may indicate a different origin for the millimeter emission, which can be explained by an advection-dominated accretion flow (ADAF) model. This model further predicts that at 230 and 340 GHz, the ADAF may dominate the radio emission over the jet.

ObjectiveTo investigate the effects of injury time, postmortem interval （PMI） and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B （Gpnmb）, and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation.MethodsTest group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test.ResultsThe expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time （P0.05）. The linear regression equation between injury time （y） and Gpnmb mRNA relative expression （x） was y=0.611 x+4.489. The back-substitution test proved that the prediction of the model was accurate.ConclusionThe expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.

Abstract The delivery of kidney care, particularly haemodialysis treatment, can result in substantial environmental impact through greenhouse emissions, natural resources depletion and waste generation. However, strategies exist to mitigate this impact and improve long term environmental sustainability for the provision of haemodialysis treatment. The nephrology community has begun taking actions to improve the environmental sustainability of dialysis, but much work remains to be done by healthcare professionals, dialysis providers and professional organisations.

Background: Results from DESTINY-Breast04 trial revealed that trastuzumab deruxtecan (T-DXd) improved both progression-free survival and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). However, the economic impact of this practice remains unclear. The purpose of this study was to evaluate the cost-effectiveness of T-DXd on HER2-low mBC from the viewpoint of U.S. payers. Methods: Using the clinical data from the DESTINY-Breast04 trial, a three-state Markov model was created to assess the economic and health effects of T-DXd versus chemotherapy. The incremental cost-effectiveness ratio (ICER) and willingness-to-pay threshold were determined and compared. One-way and probabilistic sensitivity analysis were used to measure parameter uncertainty. Results: In the overall HER2-low population, T-DXd provided additional 0.47 quality-adjusted life-years (QALYs) at an increased cost of $149,222 compared with chemotherapy, yielding an ICER of $317,494/QALY. The ICER was $353,903/QALY in the hormone receptor (HR)-positive subgroup, which decreased to $259,825/QALY in the HR-negative subgroup. The sensitivity analysis found that T-DXd would not be cost-effective in the base-case. The expected cost of T-DXd will be less than $4,281/cycle ($11.33/mg) or $1,903/cycle ($5.03/mg) to achieve a 50 or 90% cost–benefit probability, respectively. Conclusions: T-DXd provides significant health benefit for patients with HER2-low mBC compared with chemotherapy but is unlikely to be cost-effective in the United States.

Thermal environment deterioration has seriously threatened urban habitat quality and urban sustainable development. The evolution of the urban built environment (UBE) is an important cause for urban thermal environment variation. However, the dynamic effect of the UBE on the land surface temperature (LST) is rarely studied by combining the local climate zone (LCZ) theory and spatio-temporal heterogeneity. Based on a case study of Beilin District in Xi’an, China, this paper identified LCZ types of Beilin District in 2010, 2015, and 2020 using the GIS method. It also analyzed the spatial–temporal characteristics of the LST in summer based on the remote sensing retrieval method and explored the effects of the built environment on the LST by Geodetector and geographically weighted regression (GWR). The results showed the following: (1) The area share of dense building zones in Beilin District was greater than that of open building zones and natural surface zones, while the share of mid- and high-rise dense building zones continued to increase and the share of low-rise dense building zones continued to decrease during the study period. (2) The LST of different LCZ types in Beilin District was obviously different, and the LST of dense building zones was generally higher than that of open building zones and natural surface zones. Meanwhile, the LST of mid- and low-rise dense building zones increased gradually, and the LST of high-rise open building zones decreased gradually, but the overall warming area was obviously more than the cooling area. (3) The effects of the UBE factors on the LST varied greatly, with their interaction having an enhancement effect. The direct and interactive influence of the two-dimensional (2D) UBE indicators on the LST were greater than those of the three-dimensional (3D) indicators, but there was a gradual decrease in the force of the 2D indicators and a simultaneous diminution, enhancement, and invariance of the force of the 3D indicators. (4) Vegetation cover (VC) and floor area ratio (FAR) acted negatively, and the building height (BH) was changing from a positive to a negative role, with the average action intensity of VC changing from −0.27 to −0.15, FAR from −0.20 to −0.16, and BH from 0.05 to −0.04. The impervious surface area (ISA), building area (BA), and space congestion (SC) acted positively, with the average action intensity of the ISA changing from 0.12 to 0.20, BA from 0.12 to 0.19, and SC was stable at 0.04. The framework enables a deeper portrayal of LST changes in different LCZs, reflecting the direct and interactive effects of different UBE indicators on LST, as well as local variations in the impact effects and provides a basis for urban managers or planners to improve urban heat resilience.

Abstract Background To study the bacteriological characteristics, risk factors, and treatment of multi-drug resistance (MDR) organisms in patients with diabetic foot infection. Methods Patients with diabetic foot ulcer admitted to hospital from June 2018 to December 2019 (n = 180) were selected as clinical subjects. Demographic information, routine blood test, wound culture and sensitivity were collected. Risk factors of MDR bacteria were analyzed. Results Among 180 patients with diabetic foot ulcer, 146 were positive in bacterial culture, with 84 positive in MDR bacteria. A total of 182 strains were isolated, with 104 strains being multi-drug resistant. Body mass index, glycosylated hemoglobin, fasting blood glucose, triglyceride, course of ulcer, size of ulcer, peripheral neuropathy, peripheral vascular disease, osteomyelitis, peripheral blood leukocyte count, percentage of neutrophils, and previous use of antibiotics were the related factors of infection of MDR bacteria in diabetic foot ulcer patients (P

BackgroundGastric cancer (GC) is an aggressive malignant tumor with a high degree of heterogeneity, and its immune microenvironment is closely associated with tumor growth, development and drug resistance. Therefore, a classification system of gastric cancer based explicitly on the immune microenvironment context might enrich the strategy for gastric cancer prognosis and therapy.MethodsA total of 668 GC patients were collected from TCGA-STAD (n = 350), GSE15459 (n = 192), GSE57303 (n = 70) and GSE34942 (n = 56) datasets. Three immune-related subtypes (immunity-H, -M, and -L) were identified by hierarchical cluster analysis based on the ssGSEA score of 29 immune microenvironment-related gene sets. The immune microenvironment-related prognosis signature (IMPS) was constructed via univariate Cox regression, Lasso-Cox regression and multivariate Cox regression, and nomogram model combining IMPS and clinical variables was further constructed by the “rms” package. RT-PCR was applied to validate the expression of 7 IMPS genes between two human GC cell lines (AGS and MKN45) and one normal gastric epithelial cell line (GES-1).ResultsThe patients classified as immunity-H subtype exhibited highly expressed immune checkpoint and HLA-related genes, with enriched naïve B cells, M1 macrophages and CD8 T cells. We further constructed and validated a 7-gene (CTLA4, CLDN6, EMB, GPR15, ENTPD2, VWF and AKR1B1) prognosis signature, termed as IMPS. The patients with higher IMPS expression were more likely to be associated with higher pathology grade, more advanced TNM stages, higher T and N stage, and higher ratio of death. In addition, the prediction values of the combined nomogram in predicting 1-year (AUC = 0.750), 3-year (AUC = 0.764) and 5-year (AUC = 0.802) OS was higher than IMPS and individual clinical characteristics.ConclusionsThe IMPS is a novel prognosis signature associated with the immune microenvironment and clinical characteristics. The IMPS and the combined nomogram model provide a relatively reliable predictive index for predicting the survival outcomes of gastric cancer.

Hypertensive crisis and paroxysmal supraventricular tachycardia are serious adverse reactions that can lead to fatal consequences. We reported a 28-year-old woman who underwent emergency cesarean section of her first fetus due to pelvic outlet stenosis and had a hypertensive crisis, merging with paroxysmal supraventricular tachycardia after dezocine was administrated during the procedure. Her symptoms returned to normal after esmolol and urapidil were administrated. In order to rule out hypertension crisis caused by other diseases, the anesthesiologist immediately accessed the thyroid function, myocardial enzymes, catecholamines, and arterial blood gas analysis of the patient. No obvious abnormality was found in all the test results. We infer the conclusion that the symptoms of this patient during the operation were most likely related to dezocine administration. This case highlights the need to pay attention to possible malignant adverse reactions while using dezocine during cesarean section, and we recommend the immediate use of α-receptor blockers and/or β-receptor blockers in situations like to avoid serious complications caused by supraventricular tachycardia.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC).Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records.Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies.Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

We previously reported a depletion of murine regenerating islet-derived protein 2 (REG2) in pancreatic islets of glutathione peroxidase-1 (Gpx1) overexpressing (OE) mice. The present study was to explore if and how the REG2 depletion contributed to an augmented glucose stimulated insulin secretion (GSIS) in OE islets. After we verified a consistent depletion (90%, p

Exposure to heavy metals exerts toxic effects on female reproduction and embryo development. This study examined the exposure of patients with unexplained recurrent miscarriage (uRM) to multiple metals and the correlations among exposures to different metals. A total of 275 participants were enrolled, including 43 healthy women without previous miscarriage (the control group) and 232 uRM women (the case group); among these uRM women, 159 had two miscarriages (2M), 42 had three miscarriages (3M) and 31 had four or more miscarriages (≥4M). A total of 22 elements were measured in serum samples via inductively coupled plasma–mass spectrometry. The levels of calcium (104.37 mg/L vs. 92.65/93.02/92.61/92.47 mg/L) and selenium (131.85 µg/L vs. 117.80/118.04/115.88/124.35 µg/L) were higher in the controls than in the total uRM group and the 2M, 3M and ≥4M subgroups. The level of vanadium was significantly lower in the controls than in the total uRM group (0.15 µg/L vs. 0.23 µg/L), and the level of lead was lower in the controls than that in the total uRM group and the 2M, 3M and ≥4M subgroups (0.01 µg/L vs. 0.28/0.18/0.63/0.34 µg/L). After adjusting for age, body mass index and education level, calcium and selenium exposure were consistently negatively associated with miscarriage, while lead exposure was positively associated with miscarriage. In addition, the correlations among exposures to different metals slightly differed between the control and uRM groups. Therefore, changes in some metal elements in the blood might be related to the risk of uRM.

Future technologies are likely to exploit flexible heterostructures exhibiting multifunctional properties constructed from multiple materials. One technique for the synthesis of such systems relies on remote epitaxy, a method employing graphene as a sacrificial layer between a crystalline substrate and an epitaxial film. The technique can be used to create single crystal heterostructures comprised of stacked epitaxial films, their properties optimized by minimizing incompatibilities between the different materials. Details regarding nucleation and growth via remote epitaxy remain unknown, however, due to the many difficulties in studying synthesis in the growth environment with atomic-scale resolution. Here, we describe an in situ synchrotron x-ray investigation of complex oxide thin film growth on graphene by molecular beam epitaxy. Phase retrieval methods were used to reconstruct the electron density profiles from x-ray crystal truncation rods measured under different growth conditions. Our in situ observations combined with post-growth spectroscopy provide a number of key insights regarding graphene in the synthesis environment and the resulting effects on the complex oxide/graphene heterostructure.

Background: The DESTINY-Breast03 clinical trial demonstrated that trastuzumab deruxtecan (T-DXd) outperformed trastuzumab emtansine (T-DM1) in progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Considering the excessive cost of antibody-drug conjugates, the clinical value of T-DXd must be assessed by both its efficacy and cost. We compared the cost-effectiveness of T-DXd and T-DM1 for patients with HER2-positive mBC pretreated with anti-HER2 antibodies and a taxane from the perspectives of the United States (US) and China.Methods: A comprehensive Markov model based on the DESTINY-Breast03 phase III randomized clinical trial was used to compared the cost and effectiveness of T-DXd and T-DM1 for HER2-positive mBC. Data on direct medical cost and utilities were collected from published literatures. The recorded data included the costs, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER) and incremental net-health benefit (INHB). Sensitivity analysis was conducted to measure the potential uncertainty due to parameter variability. Additional subgroup cost-effectiveness analysis was performed.Results: Treatment of HER2-positive mBC with T-DXd gained 0.73 QALYs compared with T-DM1 strategy. The incremental cost was $59,942 in the US, with an ICER of $ 82,112/QALY and an INHB of 0.33 QALYs, respectively. In China, the incremental cost of T-DXd versus T-DM1 was $222,680, with an ICER of $305,041/QALY and a negative INHB of -5.18 QALYs. At willingness-to-pay (WTP) threshold of $150,000/QALY in the US and $37,653/QALY in China, the probability of T-DXd as the dominant option was 77.5 and 0.1%, respectively. The unit price of T-DXd greatly influenced the results according to one-way sensitivity analysis. To meet the 50% or 90% chance of being cost-effective, the estimated cost of T-DXd would need to be less than $17.24/mg and $12.06/mg in China, respectively.Conclusion: T-DXd is more cost-effective than T-DM1 for patients with HER2-positive mBC in the US, but not in China at current drug prices.

PurposeTo investigate the values of a 3D-printed bolus ensuring the precise postmastectomy chest wall radiation therapy for breast cancer.Methods and materialsIn the preclinical study on the anthropomorphic phantom, the 3D-printed bolus was used for dosimetry and fitness evaluation. The dosimetric parameters of planning target volume (PTV) were assessed, including Dmin, Dmax, Dmean, D95%, homogeneity index (HI), conformity index (CI), and organs at risk (OARs). The absolute percentage differences (|%diff|) between the theory and fact skin dose were also estimated, and the follow-up was conducted for potential skin side effects.ResultsIn preclinical studies, a 3D-printed bolus can better ensure the radiation coverage of PTV (HI 0.05, CI 99.91%), the dose accuracy (|%diff| 0.99%), and skin fitness (mean air gap 1.01 mm). Of the 27 eligible patients, we evaluated the radiation dose parameter (median(min–max): Dmin 4967(4789–5099) cGy, Dmax 5447(5369–5589) cGy, Dmean 5236(5171–5323) cGy, D95% 5053(4936–5156) cGy, HI 0.07 (0.06–0.17), and CI 99.94% (97.41%–100%)) and assessed the dose of OARs (ipsilateral lung: Dmean 1341(1208–1385) cGy, V5 48.06%(39.75%–48.97%), V20 24.55%(21.58%–26.93%), V30 18.40%(15.96%–19.16%); heart: Dmean 339(138–640) cGy, V30 1.10%(0%–6.14%), V40 0.38%(0%–4.39%); spinal cord PRV: Dmax 639(389–898) cGy). The skin doses in vivo were Dtheory 208.85(203.16–212.53) cGy, Dfact 209.53(204.14–214.42) cGy, and |%diff| 1.77% (0.89–2.94%). Of the 360 patients enrolled in the skin side effect follow-up study (including the above 27 patients), grade 1 was the most common toxicity (321, 89.2%), some of which progressing to grade 2 or grade 3 (32, 8.9% or 7, 1.9%); the radiotherapy interruption rate was 1.1%.ConclusionA 3D-printed bolus can guarantee the precise radiation dose on skin surface, good fitness to skin, and controllable acute skin toxicity, which possesses a great clinical application value in postmastectomy chest call radiation therapy for breast cancer.

Interleukins are assumed to be closely related to the occurrence and development of human malignant tumors, while a few of them were commonly used as diagnostic markers in clinical cancer, including lung cancer. This study aimed to explore the value of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) combined with carcinoembryonic antigen (CEA) as biomarker panel for the diagnosis and metastasis prediction of lung cancer. IL-1β, IL-6, IL-8, and CEA in serum were determined using electrochemiluminescence immunoassay (ECLIA) and flow cytometry, and the diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic fitting regression. We found that the levels of serum IL-1β, IL-6, and IL-8 showed no significant difference among squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, while they were significantly higher in the lung cancer group or benign group than those in the healthy group. The levels of IL-8 and CEA were positively correlated with clinical stages respectively. Importantly, the panel of CEA + IL-6 + IL-8 has the highest efficacy for the diagnosis of lung cancer (AUC = 0.883) among all the detected panels, while the panel of IL-8 + CEA showed the most promising predictive value for the lymph node metastasis (AUC = 0.686) and distant metastasis of lung cancer (AUC = 0.793). In conclusion, IL-6 and IL-8 could be used as promising molecular biomarkers to diagnose and predict the metastasis of lung cancer independent of pathological types, improving the specificity and sensitivity of diagnosis for lung cancer when they were combined with CEA.

Oxidative stress degrades oocytes during in vitro maturation (IVM). Catalpol, a well-known iridoid glycoside, exhibits antioxidant, anti-inflammatory, and antihyperglycemic effects. In this study, catalpol supplementation was tested on porcine oocyte IVM and its mechanisms. Corticalgranule (GC) distribution, mitochondrial function, antioxidant capacity, DNA damage degree, and real-time quantitative polymerase chain reaction were used to confirm the effects of 10 μmol/L catalpol in the maturation medium during IVM. Catalpol treatment significantly increased the first-pole rate and cytoplasmic maturation in mature oocytes. It also increased oocyte glutathione (GSH), mitochondrial membrane potential and blastocyst cell number. However, DNA damage as well as reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Mitochondrial membrane potential and blastocyst cell number were also increased. Thus, the supplementation of 10 μmol/L catalpol in the IVM medium improves porcine oocyte maturation and embryonic development.

We report multifrequency VLBI studies of the subparsec scale structure of the two-sided jets in the nearby radio galaxy NGC 4261. Our analyses include new observations using the source frequency phase referencing technique with the Very Long Baseline Array at 44 and 88 GHz, as well as archival data at 15 and 43 GHz. Our results show an extended double-sided structure at 43/44 GHz and provide a clear image of the nuclear region at 88 GHz, showing a core size of ∼0.09 mas and a brightness temperature of ∼1.3 × 10 ^9 K. Proper motions are measured for the first time in the two-sided jets, with apparent speeds ranging from 0.31 ± 0.14 c to 0.59 ± 0.40 c in the approaching jet and 0.32 ± 0.14 c in the receding jet. The jet-to-counterjet brightness ratio allows us to constrain the viewing angle to between ∼54° and 84° and the intrinsic speed to between ∼0.30 c and 0.55 c. We confirm the parabolic shape of the upstream jet on both sides of the central engine, with a power-law index of 0.56 ± 0.07. Notably, the jet collimation is found to be already completed at subparsec scales, with a transition location of about 0.61 pc, which is significantly smaller than the Bondi radius of 99.2 pc. This behavior can be interpreted as the initial confinement of the jet by external pressure from either the geometrically thick, optically thin advection-dominated accretion flows or the disk wind launched from it. Alternatively, the shape transition may also be explained by the internal flow transition from a magnetically dominated to a particle-dominated regime.

BackgroundAt present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting.MethodsWe retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan.ResultsFrom July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1–14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7–3.7), while the median OS was 33.1 months (95% CI 27.9–38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 months vs. 2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 months vs 2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 months vs 18.0 months, P = 0.072).ConclusionsFor MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.

To investigate the effect of oat bran on bread quality and the mechanism of reducing the glycemic index (GI) of bread, wheat bran (10%, w/w, flour basis), oat bran (10%), and β-glucan (0.858%) were individually added to determine the expansion of dough, the specific volume, texture, color, GI, starch digestion characteristics, and α-amylase inhibition rate of bread. The results showed that the incorporation of wheat bran and oat bran both reduced the final expanded volume of the dough, decreased the specific volume of the bread, and increased the bread hardness and crumb redness and greenness values as compared to the control wheat group. The above physical properties of bran-containing bread obviously deteriorated while the bread with β-glucan did not change significantly (p < 0.05). The GI in vitro of bread was in the following order: control (94.40) > wheat bran (69.24) > β-glucan (65.76) > oat bran (64.93). Correspondingly, the oat bran group had the highest content of slowly digestible starch (SDS), the β-glucan group had the highest content of resistant starch (RS), and the control group had the highest content of rapidly digestible starch (RDS). For the wheat bran, oat bran, and β-glucan group, their inhibition rates of α-amylase were 9.25%, 28.93%, and 23.7%, respectively. The β-glucan reduced the bread GI and α-amylase activity by intertwining with starch to form a more stable gel network structure, which reduced the contact area between amylase and starch. Therefore, β-glucan in oat bran might be a key component for reducing the GI of whole oat bread.

BackgroundPatient-derived orthotopic xenograft (PDOX) is a popular animal model for translational cancer research. Immunotherapy is a promising therapy against glioblastoma (GBM). However, the PDOX model is limited to evaluating immune-related events. Our study aims to establish GBM humanized PDOX (HPDOX) mice models to study the mechanism of anti-CTLA4 immunotherapy and immune-related adverse events (IRAEs).MethodsHPDOX models were established by culturing GBM tissues and intracranially implanting them in NSG mice. Meanwhile, peripheral blood mononuclear cells (PBMCs) were separated from peripheral blood and of GBM patients and administrated in corresponding mice. The population of CD45+, CD3+, CD4+, CD8+, and regulatory T (Treg) cells was estimated in the peripheral blood or tumor.ResultsT cells derived from GBM patients were detected in HPDOX mice models. The application of anti-CTLA4 antibodies (ipilimumab and tremelimumab) significantly inhibited the growth of GBM xenografts in mice. Moreover, residual patient T cells were detected in the tumor microenvironment and peripheral blood of HPDOX mice and were significantly elevated by ipilimumab and tremelimumab. Additionally, Treg cells were decreased in mice with IRAEs. Lastly, the proportion of CD4+/CD8+ T cells dramatically increased after the administration of ipilimumab. And the degree of IRAEs may be related to CD56+ expression in HPDOX.ConclusionsOur study established HPDOX mice models for investigating the mechanism and IRAEs of immunotherapies in GBM, which would offer a promising platform for evaluating the efficacy and IRAEs of novel therapies and exploring personalized therapeutic strategies.

Ultralow-permeability reservoirs are difficult to effectively develop using conventional technologies, so it generally produces using horizontal wells’ volume fracturing. Besides, oil wells also face the problems of short stable or no production period, rapid decline rate, and extremely low development degree. Water huff-n-puff of oil recovery technology is a quality and efficiency technology to improve the development effect of an ultralow-permeability reservoir. A systematic study on the related key influential factors of water huff-n-puff is done for improving the development effect of ultralow-permeability reservoirs. This manuscript studied the key influential factors of water huff-n-puff and related improving recovery methods using physical simulation experiments to put forward a beneficial condition for water huff-n-puff, combining with the field practice. The results show that imbibition and energy supplement are main mechanisms of water huff-n-puff; imbibition oil recovery is influenced by rock wettability, permeability, boundary condition, fracture length, water injection speed, and imbibition solution type; the stronger the water-wet reservoir rock is, the bigger the core permeability is, the longer the fracture length is, the larger the contacting area between imbibition solution and rock is, the stronger the ability of imbibition solution to change wettability, and to reduce the interfacial tension force between oil and water is, the better effect of water huff-n-puff is. So far, the field practice of water huff-n-puff has been conducted in 38 wells; the success rate can reach 92.1%, cycle oil increment of single well can reach 972 t, and accumulated oil in evaluation period can reach 36936 t, which further proves that water huff-n-puff can achieve a good effect. The effective methods to improve the development effect of an ultralow-permeability reservoir are changing reservoir physical property and supplying reservoir energy. Higher reservoir energy is good for oil flow, and better physical property can improve the displacement effect and imbibition function of injection solution. Artificial fracturing, higher injection-production ratio, and pretreatment of temporary stoppage fracturing are good methods to improve the development effect of water huff-puff.

We perform in situ synchrotron x-ray ray diffraction (SXRD)/reflection high energy electron diffraction (RHEED) studies on the growth of complex oxide thin films by molecular beam epitaxy. The unique deposition chamber, located at the Advanced Photon Source, allows the preparation of complex oxide samples with monolayer precision and facilitates the formation of direct correlations between in situ x-ray studies and the more prevalent RHEED investigations. Importantly, because SXRD and RHEED probe different atomic-scale processes during thin film synthesis, their concomitant use enables the extraction of details concerning growth behavior that one cannot determine from either probe alone. We describe the results of such in situ studies on the epitaxial growth of perovskite LaNiO3 on (La0.18Sr0.82)(Al0.59Ta0.41)O3 (001). We find that during the earliest stages of growth, the RHEED and x-ray signals do not agree with each other, demonstrating that while regular RHEED oscillations may imply high quality growth, the film–substrate interface can undergo significant changes during deposition due to the occurrence of interdiffusion at the growth temperature.

The ‘stress-gradient hypothesis’ predicts increasing facilitative interactions with increasing environmental stress, but it remains unclear if the prevailing type of interaction (i.e. facilitative or competitive) between dominant and subordinate plant species occurring in harsh environments is dependent on the plant functional type. In addition, most plant-species removal experiments in grasslands are short-term (1–2 years), which may imprecisely reflect transient effects arising from methodological limitations. We conducted a dominant species removal experiment in a subalpine ecosystem, containing a mosaic of grass-dominated and shrub-dominated community patches, both of which are common in the subalpine zone of the Qinghai-Tibetan Plateau. We examined the direction and magnitude of the effects of three co-dominant grass and a dominant shrub species on subordinate species richness and biomass over a 6-year period. Removal of the dominant grass species alleviated their competitive pressure on subdominant grasses, which resulted in similar total and grass biomass detected in the final year of the study. By contrast, shrub removal showed no effects on its subordinate species biomass. Furthermore, neither the removal of the dominant shrubs nor the grasses altered their respective subordinate species richness. Thus, in subalpine ecosystems that experience harsh environmental conditions, our results showed that the direction of interactive effects of dominant plant species on subordinate species may be dependent on the plant functional type and are not necessarily facilitative. Furthermore, we showed that longer-term plant-removal experiment observations may be required to better determine the effects of species removal for this subalpine and other montane ecosystem(s).

The interface reconstruction in perovskite heterostructures caused by interfacial octahedral tilt/rotation and its effects on the spin, charge, and orbital degrees of freedom is a very attractive topic for correlated oxides. Here, we present a systematic investigation on tensely strained (110)-LaCoO3/La2/3Sr1/3MnO3/LaCoO3 trilayers, focusing on orbital reconstruction and accompanied effects. The most remarkable finding is the reordering of the energy levels of Mn-3d orbitals at the interface: the low-lying orbital becomes dx2-y2 for sandwiched La2/3Sr1/3MnO3 rather than d3z2-r2 as expected for a bare La2/3Sr1/3MnO3 film. Interlayer charge transfer via dx2-y2 orbitals is further detected as a driving force of orbital reconstruction. Due to spin–orbit coupling, the charge/orbital reconstruction produces a chain effect on the spin degree of freedom of the La2/3Sr1/3MnO3 layer, resulting in a dramatic spin reorientation by 90° in a film plane. The present work demonstrates how to tune macroscopic properties of correlated oxides via mutual coupling between different degrees of freedom.

We have prepared a kind of new type of flavonoid nitrogen mustard derivatives with broad-spectrum antitumor activity, which have not been reported in the literature. In the process of preparing intermediate (the flavonoid diethanolamine derivatives) of the target compound, we found that the reasonable separation method is silica gel column chromatography with eluent (MeOH/CH2Cl2, 1:40). The experimental results show that the composition of eluent is an important factor to get high yield of the intermediate, which will directly affect the final yield of the target compound. Acetonitrile is the suitable solvent in the reaction system, and the optimized reaction condition is reaction under reflux condition for 48 hours. Several new flavonoid nitrogen mustard derivatives were synthesized with high yield using the above method. • A method for the synthesis of flavonoid nitrogen mustard derivatives was introduced. • The reasonable purification conditions and the optimized reaction time were recommended.