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Abstract To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)—and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5−40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p

Abstract This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

Abstract There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p

Abstract This study focuses on the prediction and management of carbon emissions (CE) under the backdrop of global warming, with a particular emphasis on developing spatial planning strategies for urban clusters. In this context, we integrate artificial intelligence technologies to devise an optimized spatial analysis method based on the attributes of multi-source, urban-level spatio-temporal big data on CE. This method enhances both the accuracy and interpretability of CE data processing. Our objectives are to accurately analyze the current status of CE, predict the future spatial distribution of urban CE in the Yangtze River Delta (YRD), and identify key driving factors. We aim to provide pragmatic recommendations for sustainable urban carbon management planning. The findings indicate that: (1) the algorithm designed by us demonstrates excellent fitting capabilities in the analysis of CE data in the YRD, achieving a fitting accuracy of 0.93; (2) it is predicted that from 2025 to 2030, areas with higher CE in the YRD will be primarily concentrated in the 'Provincial Capital Belt' and the 'Heavy Industry Belt'; (3) the economic foundation has been identified as the most significant factor influencing CE in the YRD; (4) projections suggest that CE in the YRD are likely to peak by 2030.

Abstract Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.

Abstract The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3–4. In addition to stage, intrahepatic metastasis and Child–Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p

Abstract The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients’ perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach’s α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P

Abstract This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Abstract We performed this cohort study to investigate whether the myocardial bridge (MB) affects the fat attenuation index (FAI) and to determine the optimal cardiac phase to measure the volume and the FAI of pericoronary adipose tissue (PCAT). The data of 300 patients who were diagnosed with MB of the left anterior descending (LAD) coronary artery were retrospectively analyzed. All of patients were divided into the MB group and the MB with atherosclerosis group. In addition, 104 patients with negative CCTA results were enrolled as the control group. There was no significant difference between FAI values measured in systole and diastole (P > 0.05). There was no significant difference in FAI among the MB group, the MB with atherosclerosis group, and the control group (P > 0.05). In MB with atherosclerosis group, LAD stenosis degree (

Abstract A wide variety of bridge barriers are used on highways. The bearing capacities of different types of deck slabs are measured in this study by applying the yield line theory to determine the worst-case scenario. An improved configuration for the worst-case barrier base and deck slab is developed, namely the universal double-beam assembled bridge barrier, which can enhance the safety performance of exiting concrete-base bridge barriers. According to the simulated impact test results, the new barrier meets SS-level requirements in terms of containment, redirective, and buffering performance as specified in the Standard for Safety Performance Evaluation of Highway Barriers (JTG B05-01-2013). The barrier structure’s compatibility with various bases is also analyzed. SS-level impact tests are conducted on real vehicles, including cars, buss, and trucks. The results show that the safety performance of the new barrier configuration reaches SS-level, and the barrier is universally compatible with concrete bases with a height of 63 cm and above.

Abstract Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.

Abstract It has been a decade since the first extensive study on the internet's adoption and use was conducted. Circumstances have changed in the last decade internet has become an essential need for every human being. Socio-psychological, economic, and personal factors play a significant role in shaping human behaviour. But their role in shaping consumer behaviour toward 5G is still unexplored. In order to determine the impact of socio-psychological elements on 5G technology adoption intention, the study integrated curiosity, perceived value, functional value, and environmental awareness into UTAUT2 and analyzed how they interact. Instead of relying on linear models, this study employed a dual-stage SEM-ANN approach because customers' decision-making process to adopt new technology is complex. Valid responses from 840 respondents were collected, investigated, and ranked using the deep learning ANN approach. All predictors were found statistically significant except social influence. ANN sensitivity analysis revealed that newly integrated predictors (environmental awareness, curiosity) are surprisingly the most important predictors, followed by facilitating conditions and perceived satisfaction. SEM-ANN hybrid two-step deep learning approach explained 83.6% variance higher than the baseline model (UTAUT2). The study improved UTAUT2 by adding new variables and expanding its canvas to predict user technology adoption. This will show how consumers react to 5G services and help telecoms grow into new markets.

Abstract Lysophosphatidylcholine (LPC) was previously found to show neuroprotective effect on nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) induced signalings. Also, numerous studies reported the emerging roles of long noncoding RNAs (LncRNAs) involved in neurodegenerative disease. However, the biological mechanism of LPC and expression profile of lncRNAs has not been reported. Here, lncRNAs in PC12 cells under LPC and NGF treatment were analyzed using high throughput sequencing technology for the first time. We identified 564 annotated and 1077 novel lncRNAs in PC12 cells. Among them, 121 lncRNAs were differentially expressed in the PC12 cells under LPC stimulation. KEGG analysis showed that differentially expressed mRNAs co-expressed with lncRNAs mainly enriched in ribosome, oxidative phosphorylation, Parkinson’s disease, Huntington’s disease and Alzheimer’s disease etc. LncRNA-mRNA network analysis showed that lncRNA ENSRNOT00000082515 had interactions with 626 different mRNAs suggesting that lncRNA ENSRNOT00000082515 probably play vital role. Finally, sequencing data were validated by qRT-PCR for ENSRNOT00000084874, ENSRNOT00000082515, LNC_001033 forward Fgf18, Vcam1, and Pck2.

Abstract To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15–20+6 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer–lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.

Abstract To determine whether smoking has adverse effects on postoperative complications following spine cervical surgery (PROSPERO 2021: CRD42021269648). We searched PubMed, Embase, Cochrane Library, and Web of Science through 13 July 2021 for cohort and case–control studies that investigated the effect of smoking on postoperative complications after cervical spine surgery. Two researchers independently screened the studies and extracted data according to the selection criteria. The meta-analysis included 43 studies, including 27 case–control studies and 16 cohort studies, with 10,020 patients. Pooled estimates showed that smoking was associated with overall postoperative complications (effect estimate [ES] = 1.99, 95% confidence interval [CI]: 1.62–2.44, p

Abstract The study aimed to evaluate the prognostic significance of preoperative systemic inflammatory biomarkers including albumin to globulin ratio (AGR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) and establish a nomogram in hepatocellular carcinoma (HCC) patients after microwave ablation (MWA). 192 HCC patients receiving MWA as initial therapy from the first ward of hepatobiliary surgery were classified as training cohort. Whereas, 84 patients from the second of hepatobiliary surgery were classified as validation cohort. Kaplan–Meier (KM) method and univariate analyses showed that AGR, NLR, LMR, and PLR were significantly associated with OS in the training cohort. Multivariate analysis including clinicopathologic features screened out independent predictors including ascites, tumor size, cancer embolus, AGR, and PLR. Based on those variables, a nomogram for predicting OS was established. The C-index was 0.794 in the training cohort and 0.772 in the validation cohort. Calibration plots identified the nomogram performed well with an ideal model. Compared with Barcelona Clinic Liver Cancer (BCLC) staging system and simple tumor size, the nomogram showed better predictive ability. Besides, the nomogram discovered the highest diagnostic accuracy in predicting postoperative clinical outcome than the combination of the present models with tumor size. In conclusion, the constructed nomogram could accurately predict individualized survival probability and might support clinician in individual treatment optimization and clinical decision-making.

Abstract Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P

Abstract Ciliated protozoans form dormant cysts for survival under adverse conditions. The molecular mechanisms regulating this process are critical for understanding how single-celled eukaryotes adapt to the environment. Despite the accumulated data on morphology and gene coding sequences, the molecular mechanism by which lncRNAs regulate ciliate encystment remains unknown. Here, we first detected and analyzed the lncRNA expression profile and coexpressed mRNAs in dormant cysts versus vegetative cells in the hypotrich ciliate Pseudourostyla cristata by high-throughput sequencing and qRT-PCR. A total of 853 differentially expressed lncRNAs were identified. Compared to vegetative cells, 439 and 414 lncRNAs were upregulated and downregulated, respectively, while 47 lncRNAs were specifically expressed in dormant cysts. A lncRNA-mRNA coexpression network was constructed, and the possible roles of lncRNAs were screened. Three of the identified lncRNAs, DN12058, DN20924 and DN30855, were found to play roles in fostering encystment via their coexpressed mRNAs. These lncRNAs can regulate a variety of physiological activities that are essential for encystment, including autophagy, protein degradation, the intracellular calcium concentration, microtubule-associated dynein and microtubule interactions, and cell proliferation inhibition. These findings provide the first insight into the potentially functional lncRNAs and their coexpressed mRNAs involved in the dormancy of ciliated protozoa and contribute new evidence for understanding the molecular mechanisms regulating encystment.

Abstract Severe osteoporotic vertebral compression fractures (OVCFs) were considered as relative or even absolute contraindication for vertebroplasty and kyphoplasty and these relevant reports are very limited. This study aimed to evaluate and compare the efficacy of vertebroplasty with high-viscosity cement and conventional kyphoplasty in managing severe OVCFs. 37 patients of severe OVCFs experiencing vertebroplasty or kyphoplasty were reviewed and divided into two groups, according to the procedural technique, 18 in high-viscosity cement percutaneous vertebroplasty (hPVP) group and 19 in conventional percutaneous kyphoplasty (cPKP) group. The operative time, and injected bone cement volume were recorded. Anterior vertebral height (AVH), Cobb angle and cement leakage were also evaluated in the radiograph. The rate of cement leakage was lower in hPVP group, compared with cPKP group (16.7% vs 47.4%, P = 0.046). The patients in cPKP group achieved more improvement in AVH and Cobb angle than those in hPVP group postoperatively (37.2 ± 7.9% vs 43.0 ± 8.9% for AVH, P = 0.044; 15.5 ± 4.7 vs 12.7 ± 3.3, for Cobb angle, P = 0.042). At one year postoperatively, there was difference observed in AVH between two groups (34.1 ± 7.4 vs 40.5 ± 8.7 for hPVP and cPKP groups, P = 0.021), but no difference was found in Cobb angle (16.6 ± 5.0 vs 13.8 ± 3.8, P = 0.068). Similar cement volume was injected in two groups (2.9 ± 0.5 ml vs 2.8 ± 0.6 ml, P = 0.511). However, the operative time was 37.8 ± 6.8 min in the hPVP group, which was shorter than that in the cPKP group (43.8 ± 8.2 min, P = 0.021). In conclusion, conventional PKP achieved better in restoring anterior vertebral height and improving kyphotic angle, but PVP with high-viscosity cement had lower rate of cement leakage and shorter operative time with similar volume of injected cement.

Abstract The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p

Abstract Senescence is a degenerative process triggered by intricate and coordinated regulatory networks, and the mechanisms of age-dependent senescence and stress-induced premature senescence still remain largely elusive. Thus we selected leaf samples of developmental senescence (DS) and premature senescence (PS) to reveal the regulatory divergence. Senescent leaves were confirmed by yellowing symptom and physiological measurement. A total of 1171 and 309 genes (DEGs) were significantly expressed respectively in the whole process of DS and PS. Up-regulated DEGs in PS were mostly related to ion transport, while the down-regulated DEGs were mainly associated with oxidoreductase activity and sesquiterpenoid and triterpenoid biosynthesis. In DS, photosynthesis, precursor metabolites and energy, protein processing in endoplasmic reticulum, flavonoid biosynthesis were notable. Moreover, we found the vital pathways shared by DS and PS, of which the DEGs were analyzed further via protein–protein interaction (PPI) network analysis to explore the alteration responding to two types of senescence. In addition, plant hormone transduction pathway was mapped by related DEGs, suggesting that ABA and ethylene signaling played pivotal roles in formulating the distinction of DS and PS. Finally, we conducted a model containing oxidative stress and ABA signaling as two hub points, which highlighted the major difference and predicted the possible mechanism under DS and PS. This work gained new insight into molecular divergence of developmental senescence and premature senescence and would provide reference on potential mechanism initiating and motivating senescence for further study.

Abstract Human exposure to lead mainly occurs by ingestion of contaminated food, water and soil. Blocking lead uptake in the gastrointestinal tract is a novel prevention strategy. Whole-cell biosorbent for lead was constructed with PbrR genetically engineered on the cell surface of Escherichia coli (E. coli), a predominant strain among intestinal microflora, using lipoprotein (Lpp)-OmpA as the anchoring protein. In vitro, the PbrR displayed cells had an enhanced ability for immobilizing toxic lead(II) ions from the external media at both acidic and neutral pH, and exhibited a higher specific adsorption for lead compared to other physiological two valence metal ions. In vivo, the persistence of recombinant E. coli in the murine intestinal tract and the integrity of surface displayed PbrR were confirmed. In addition, oral administration of surface-engineered E. coli was safe in mice, in which the concentrations of physiological metal ions in blood were not affected. More importantly, lead associated with PbrR-displayed E. coli was demonstrated to be less bioavailable in the experimental mouse model with exposure to oral lead. This is reflected by significantly lower blood and femur lead concentrations in PbrR-displayed E. coli groups compared to the control. These results open up the possibility for the removal of toxic metal ions in vivo using engineered microorganisms as adsorbents.

Abstract Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation of cell motility, invasion and metastasis. AKT activation is known to promote metastasis, however under certain circumstances, it also shows an inhibitory activity on metastatic processes, and the cause of such conflicting results is largely unclear. Here we found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells. The allosteric AKT inhibitor MK-2206 promoted metastasis of KRAS-mutated A549 cells in vivo. We next identified that the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS) and LAMC2 protein level were increased with AKT1 inhibition, and MARCKS or LAMC2 knockdown abrogated migration and invasion induced by AKT1 inhibition. This study unravels an anti-metastatic role of AKT1 in the NSCLC cells with KRAS or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback loop in this regulation.

Abstract Component-based Chinese medicine (CCM) is derived from traditional Chinese medicine but produced with modern pharmaceutical standard and clearer clinical indications. However, it still faces challenges of defining individual component contribution in the complex formula. Using QiShenYiQi (QSYQ) as a model CCM, we investigated the role of Dalbergia odorifera (DO), an herbal component, in preventing myocardial damage. We showed that in vitro, QSYQ exerted considerable protective activities on cardiomyocytes from H2O2-induced mitochondrial dysfunction with or without DO. However, in isolated rat hearts, myocardial protection by QSYQ was significantly weakened without DO. In everted gut sac model, DO significantly enhanced absorption of the major QSYQ ingredients in different regions of rat intestine. Finally, in in vivo mouse model of doxorubicin (DOX)-induced myocardial damage, only QSYQ, but not QiShenYiQi without DO (QSYQ-DO), exerted a full protection. Taken together, our results showed that instead of directly contributing to the myocardial protection, Dalbergia odorifera facilitates the major active ingredients absorption and increases their efficacy, eventually enhancing the in vivo potency of QSYQ. These findings may shed new lights on our understanding of the prescription compatibility theory, as well as the impacts of “courier herbs” in component-based Chinese medicine.

Abstract Adequately understanding band inversion mechanism, one of the significant representations of topological phase, has substantial implications for design and regulation of topological insulators (TIs). Here, by identifying an unconventional band inversion, we propose an intrinsic quantum spin Hall (QSH) effect in iodinated group-V binary (ABI2) monolayers with a bulk gap as large as 0.409 eV, guaranteeing its viable application at room temperature. The nontrivial topological characters, which can be established by explicit demonstration of Z2 invariant and gapless helical edge states, are derived from the band inversion of antibonding states of p x,y orbitals at the K point. Furthermore, the topological properties are tunable under strain engineering and external electric field, which supplies a route to manipulate the spin/charge conductance of edge states. These findings not only provide a new platform to better understand the underlying origin of QSH effect in functionalized group-V films, but also are highly desirable to design large-gap QSH insulators for practical applications in spintronics.

Abstract Aspergillus and its poisonous mycotoxins are distributed worldwide throughout the environment and are of particular interest in agriculture and food safety. In order to develop a specific method for rapid detection of Aspergillus flavus to forecast diseases and control aflatoxins, a nanobody, PO8-VHH, highly reactive to A. flavus was isolated from an immunized alpaca nanobody library by phage display. The nanobody was verified to bind to the components of extracellular and intracellular antigen from both A. flavus and A. parasiticus. To construct a sandwich format immunoassay, polyclonal antibodies against Aspergillus were raised with rabbits. Finally, a highly selective nanobody-polyclonal antibody sandwich enzyme-linked immunosorbent assay was optimized and developed. The results revealed that the detection limits of the two fungi were as low as 1 μg mL−1, and that it is able to detect fungal concentrations below to 2 μg mg−1 of peanut and maize grains in both artificially and naturally contaminated samples. Therefore, we here provided a rapid and simple method for monitoring Aspergillus spp. contamination in agricultural products.

Abstract Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim to develop a three-dimensional (3D) microfluidic cell invasion model to determine the dynamic process. In this model, collective invasion of breast cancer cells is induced by the concentration gradient of fetal bovine serum. We find that breast cancer cells adopt a collective movement rather than a random manner when the cells invade into extracellular matrix. The leading cells in the collective movement exhibit an increased expression of an Aurora kinase family protein - AURKA compared with the follower cells. Inhibition of AURKA kinase activity by VX680 or AKI603 significantly reduces the phosphorylation of ERK1/2 (Thr202/Tyr204) and collective cohort formation. Together, our study illustrates that AURKA acts as a potential therapeutic target for suppressing the process of tumor collective invasion. The 3D microfluidic cell invasion model is a reliable, measurable and dynamic platform for exploring potential drugs to inhibit tumor collective invasion.