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Abstract Background Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Abstract Background Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. Methods This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. Results During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear

Abstract Background N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. Methods CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. Results The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. Conclusion The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05–3.39), 1.62 (1.23–2.12), 2.06 (1.73–2.45), 1.20 (1.16–1.25), and 1.07 (1.05–1.08) per 10 μg/m3 increase in PM2.5, PM2.5–10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33–1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

In order to effectively alleviate the corrosion of the filter element and column of the hydraulic support, five-membered nitrogen heterocyclic imidazoline group was introduced on the basis of sebacic acid and L-glutamic acid by acylation-cyclization reaction, and xylene was used as solvent and water-carrying agent. Two kinds of corrosion inhibitor of bicyclic imidazoline quaternary ammonium sebacate GM-1 and L-glutamic acid bicyclic imidazoline quaternary ammonium salt LM-1 were synthesized with excellent corrosion inhibition performance for hydraulic support concentrate. The water solubility is enhanced by using sodium chloroacetate as a quaternary ammonium salting agent. Its structure was confirmed by infrared spectroscopy. The corrosion inhibition performance of two additives on HT300 gray cast iron in 330 mg/L NaCl corrosion medium was studied by corrosion weight loss, water contact angle, electrochemical and quantum chemical methods. Adsorption mode and corrosion inhibition mechanism of two additive molecules on the surface of HT300 gray cast iron. The research results show that both additives have good corrosion inhibition performance on HT300 gray cast iron immersed in 330 mg/L NaCl corrosive medium. The corrosion rate reached 95.89% and 85.79% respectively. Electrochemistry shows that both additives are anodic corrosion inhibitors and inhibit the transfer of charge between the graphite electrode and gray cast iron. The adsorption mode of additives on the surface of cast iron satisfies the Langmuir monolayer adsorption, and the Gibbs free energies are −35.361 kJ/mol and −31.093 kJ/mol respectively. It shows that the adsorption is a spontaneous physical adsorption and chemical adsorption process, and chemical adsorption is the main. When adding additives with a mass concentration of 0.5%, the water contact angles on the surface of HT300 gray cast iron soaked in GM-1 and LM-1 reached 86.24° and 82.34°, respectively, indicating that the corrosion of Cl− was isolated through the presence of additive molecules in the hydrophobic film is formed on the surface of HT300 gray cast iron.Quantum chemistry shows that adsorption films are formed through coordination and feedback bonds. Compared with LM, GM is easier to adsorb on the surface of HT300 gray cast iron because the empty 3d orbital of metal is easier to give electrons to form coordination bonds and the energy barrier required for adsorption is smaller.

Abstract Background In clinical practice, reducing unnecessary biopsies for mammographic BI-RADS 4 lesions is crucial. The objective of this study was to explore the potential value of deep transfer learning (DTL) based on the different fine-tuning strategies for Inception V3 to reduce the number of unnecessary biopsies that residents need to perform for mammographic BI-RADS 4 lesions. Methods A total of 1980 patients with breast lesions were included, including 1473 benign lesions (185 women with bilateral breast lesions), and 692 malignant lesions collected and confirmed by clinical pathology or biopsy. The breast mammography images were randomly divided into three subsets, a training set, testing set, and validation set 1, at a ratio of 8:1:1. We constructed a DTL model for the classification of breast lesions based on Inception V3 and attempted to improve its performance with 11 fine-tuning strategies. The mammography images from 362 patients with pathologically confirmed BI-RADS 4 breast lesions were employed as validation set 2. Two images from each lesion were tested, and trials were categorized as correct if the judgement (≥ 1 image) was correct. We used precision (Pr), recall rate (Rc), F1 score (F1), and the area under the receiver operating characteristic curve (AUROC) as the performance metrics of the DTL model with validation set 2. Results The S5 model achieved the best fit for the data. The Pr, Rc, F1 and AUROC of S5 were 0.90, 0.90, 0.90, and 0.86, respectively, for Category 4. The proportions of lesions downgraded by S5 were 90.73%, 84.76%, and 80.19% for categories 4 A, 4B, and 4 C, respectively. The overall proportion of BI-RADS 4 lesions downgraded by S5 was 85.91%. There was no significant difference between the classification results of the S5 model and pathological diagnosis (P = 0.110). Conclusion The S5 model we proposed here can be used as an effective approach for reducing the number of unnecessary biopsies that residents need to conduct for mammographic BI-RADS 4 lesions and may have other important clinical uses.

Background: Endoscopic therapy is an optional strategy for the treatment of esophageal cancer (EC) under an early stage, especially stage T1a. However, its efficacy in the treatment of T1b EC has not been thoroughly assessed. We investigated the efficacy of esophagectomy, endoscopic therapy, as well as chemoradiotherapy in patients with T1bN0M0 EC. Methods: The Surveillance, Epidemiology, and End Results database (SEER) was employed to identify patients diagnosed with T1bN0M0 EC. Patient demographics were compared among the endoscopic therapy, esophagectomy, and chemoradiotherapy groups. Our study employed Kaplan-Meier analysis and Cox regression model to evaluate patient outcomes and long-term survival rates. The overall survival (OS) and cancer-specific survival (CSS) rates were compared among patients with EC who underwent endoscopic therapy or esophagectomy, employing propensity score matching (PSM). Results: A total of 820 patients diagnosed with T1bN0M0 EC were identified. The number of patients who received endoscopic therapy, esophagectomy, and chemoradiotherapy was 173, 556, and 91, respectively. Patients subjected to endoscopic therapy and esophagectomy had greatly longer OS and CSS than those who underwent chemoradiotherapy. Patients treated with esophagectomy had longer OS than endoscopic therapy patients, but there were no differences in CSS between the two groups. PSM generated 153 patient pairs among T1bN0M0 patients, demonstrating that both the esophagectomy and endoscopic therapy groups exhibited comparable OS and CSS rates. Conclusion: Endoscopic therapy and esophagectomy were associated with a significant survival advantage compared with chemoradiotherapy in patients with T1bN0M0 EC. In contrast, after PSM, among the EC patients with stage T1bN0M0, OS and CSS did not differ after endoscopic therapy or esophagectomy. These results indicate that endoscopic therapy could be a viable alternative to esophagectomy in patients diagnosed with T1bN0M0 EC.

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006–2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM2.5, PM10, NO2, and NOX increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65–0.76) for PM2.5, 0.69 (95 % CI: 0.64–0.75) for PM10, 0.70 (95 % CI: 0.64–0.75) for NO2, and 0.70 (95 % CI: 0.64–0.75) for NOX. No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings.

Abstract Background The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution. Methods UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5−10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79–0.86) and 0.73 (95% CI, 0.70–0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14–1.24), 1.06 (1.02–1.11), 1.13 (1.08–1.18), and 1.19 (1.14–1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend

Signal detection in massive MIMO systems faces many challenges. The minimum mean square error (MMSE) approach for massive multiple-input multiple-output (MIMO) communications offer near to optimal recognition but require inverting the high-dimensional matrix. To tackle this issue, a Gauss–Seidel (GS) detector based on conjugate gradient and Jacobi iteration (CJ) joint processing (CJGS) is presented. In order to accelerate algorithm convergence, the signal is first initialized using the optimal initialization regime among the three options. Second, the signal is processed via the CJ Joint Processor. The pre-processed result is then sent to the GS detector. According to simulation results, in channels with varying correlation values, the suggested iterative scheme’s BER is less than that of the GS and the improved iterative scheme based on GS. Furthermore, it can approach the BER performance of the MMSE detection algorithm with fewer iterations. The suggested technique has a computational complexity of O(U2), whereas the MMSE detection algorithm has a computational complexity of O(U3), where U is the number of users. For the same detection performance, the computational complexity of the proposed algorithm is an order of magnitude lower than that of MMSE. With fewer iterations, the proposed algorithm achieves a better balance between detection performance and computational complexity.

Yeast β-glucan is a polysaccharide purified from the Saccharomyces cerevisiae cell wall, and its multiple biological activities are essential for immune regulation. However, the effect of β-glucan on the intestinal immune response during colitis-associated colorectal cancer (CAC) is unclear. Here, we explore the possible role of β-glucan in the development of CAC. Wild type (WT) mice with CAC induced by azoxmethane (AOM) and dextran sodium sulfate (DSS) had fewer tumors than untreated mice after oral β-glucan because of increased antitumor dendritic cells (DCs) in the tumor microenvironment, resulting in more CD8+ T cells and the production of related cytokines. β-glucan also increased resistance to DSS-induced chronic colitis by reshaping the inflammatory microenvironment. These data suggest that β-glucan improves experimental intestinal inflammation and delays the development of CAC. Therefore, β-glucan is feasible for treating chronic colitis and CAC in clinical practice.

Immunotherapy can reverse tumor immune escape by suppressing immune checkpoints. Lymphocyte activation gene 3 (LAG3) is an important checkpoint and its role in colorectal cancer is not clear. In this study, we investigated LAG3 protein expression and its correlation with clinicopathologic parameters. The expression of LAG3 protein was assessed in 150 surgically resected colorectal cancer tissue samples by immunohistochemistry. The relationship between LAG3 expression and clinicopathological parameters, MSI status and survival was statistically analyzed. LAG3 protein was not expressed in colorectal cancer cells, and was expressed on the tumor-infiltrating lymphocytes (TILs) in 31 out of 150 (20.7%) colorectal cancer samples. Positive expression of LAG3 in TILs is associated with lymph node metastasis (p < 0.001), TNM stage (p = 0.024) and MSI-H (p = 0.035). No significant relationship was found between LAG3 expression and gender, age, tumor location, tumor invasion depth, and differentiation. LAG3 expression is associated with longer overall survival (p = 0.045). Our data show LAG3 expression on TILs in parts of CRC tissue. Positive expression of LAG3 was associated with advanced tumor stage, MSI-H and a poor prognosis. We conclude that LAG3 is an important checkpoint gene in CRC and may be a potential marker for prognosis of CRC.

Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

Abstract Here, this work presents an air-stable ultrabright inverted organic light-emitting device (OLED) by using zinc ion-chelated polyethylenimine (PEI) as electron injection layer. The zinc chelation is demonstrated to increase the conductivity of the PEI by three orders of magnitude and passivate the polar amine groups. With these physicochemical properties, the inverted OLED shows a record-high external quantum efficiency of 10.0% at a high brightness of 45,610 cd m−2 and can deliver a maximum brightness of 121,865 cd m−2. Besides, the inverted OLED is also demonstrated to possess an excellent air stability (humidity, 35%) with a half-brightness operating time of 541 h @ 1000 cd m−2 without any protection nor encapsulation.

The ligand-tailored SnO2 QDs ETL with multi-functional terminal groups in situ refines the buried interfaces with both the perovskite and transparent electrode via enhanced interface binding and perovskite passivation.

ObjectiveTo study the similarities and differences in the clinical efficacy of aripiprazole and quetiapine in Chinese patients with bipolar depression through meta-analysis. Additionally, to provide evidence of aripiprazole in treatment for bipolar depression.MethodsWe searched Chinese literature related to the study of aripiprazole and quetiapine in treatment for bipolar depression, among which results such as comments, letters, reviews, and case reports were excluded. The clinical efficacy between aripiprazole and quetiapine was synthesized and discussed.ResultA total of 1,546 subjects were included in 17 studies. The random effect model was used to review the data by RevMan 5.2. The results showed that there was no significant difference in the remission rate between patients treated with aripiprazole and quetiapine evidenced by the scale used to evaluate the patients being treated for bipolar depression (221/501 vs. 193/501, Z = 1.12, P = 0.26). But the results also showed that the remission rate of aripiprazole with lithium carbonate was significantly higher than quetiapine with lithium carbonate in the treatment of bipolar depression (111/232 vs. 69/232, Z = 3.92, P < 0.0001). The results showed that the effective rate of aripiprazole was similar to quetiapine (426/572 vs. 386/572, Z = 2.70, P = 0.007). Overall, there was no difference in the Hamilton Rating Scale for Depression (HAMD) score between patients treated with aripiprazole and quetiapine (Z = 1.68, P = 0.09). The results also show that the drop-out rate of aripiprazole was similar to quetiapine in the treatment of patients with bipolar depression (Z = 1.80, P = 0.07).ConclusionAs an atypical antipsychotic, aripiprazole may be similar to quetiapine for treating bipolar depression with similar drop-out and higher remission rates when combined with lithium carbonate. However, the results of this study need to be read with caution given the poor quality of collected/analyzed literature.

Abstract Background We investigated college students’ attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). Methods We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. Results A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. Conclusions Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

Abstract Grain boundaries in organic–inorganic halide perovskite solar cells (PSCs) have been found to be detrimental to the photovoltaic performance of devices. Here, we develop a unique approach to overcome this problem by modifying the edges of perovskite grain boundaries with flakes of high-mobility two-dimensional (2D) materials via a convenient solution process. A synergistic effect between the 2D flakes and perovskite grain boundaries is observed for the first time, which can significantly enhance the performance of PSCs. We find that the 2D flakes can conduct holes from the grain boundaries to the hole transport layers in PSCs, thereby making hole channels in the grain boundaries of the devices. Hence, 2D flakes with high carrier mobilities and short distances to grain boundaries can induce a more pronounced performance enhancement of the devices. This work presents a cost-effective strategy for improving the performance of PSCs by using high-mobility 2D materials.

It is crucial to diagnose breast cancer early and accurately to optimize treatment. Presently, most deep learning models used for breast cancer detection cannot be used on mobile phones or low-power devices. This study intended to evaluate the capabilities of MobileNetV1 and MobileNetV2 and their fine-tuned models to differentiate malignant lesions from benign lesions in breast dynamic contrast-enhanced magnetic resonance images (DCE-MRI).

A thorough investigation on the reactions and morphologies of Mg particles and Mg/Teflon/Viton (MTV) during oxidation were conducted via thermal gravity-differential scanning calorimetry (TG-DSC) and scanning electronic microscopy. The results showed that the oxidation of Mg is fast. It merely changed the metallic luster of Mg before 550 °C, and only a few particles changed to a white irregular shape at 600 °C. However, all of the Mg particles oxidized to porous irregular shaped MgO at 650 °C. Herein, the oxidation of Mg particles ended by its melting point, and the whole process is a solid–gas-phase reaction. On the other hand, when MTV reacted in air, the reaction could be divided into two stages: the fluorination of Mg and the oxidation of the exceeded Mg. In the first stage, a dense MgF2 shell was formed by the solid–solid fluorination. The dense MgF2 shell could impede the oxidation of Mg. As a result, the oxidation of Mg began after its melting. Furthermore, liquid Mg could vaporize at higher temperature, which could burst out from the MgF2 shell and react with oxygen. The MgF2 shell exhibited a dense feature, not only protecting the Mg particles from the heterogeneous oxidation at lower temperature, but also facilitates the homogeneous oxidation at higher temperature.

BackgroundNon-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019–2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza.MethodsWe used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore.ResultsWe found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019–2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50–99.48% during the period of compulsory interventions in the 2019–2020 season compared to the same period in preceding years in the four countries.ConclusionThese findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.

In this paper, we introduce iterative learning control (ILC) schemes with varying trial lengths (VTL) to control impulsive multi-agent systems (I-MAS). We use domain alignment operator to characterize each tracking error to ensure that the error can completely update the control function during each iteration. Then we analyze the system’s uniform convergence to the target leader. Further, we use two local average operators to optimize the control function such that it can make full use of the iteration error. Finally, numerical examples are provided to verify the theoretical results.

Surface states of topological semimetals may give rise to unusual transport properties and topological superconductivity. Here, the H-T phase diagram of AuSn4 is experimentally established, displaying 2D superconductivity, Bose metal behavior, and normal-state magnetotransport driven by surface states.

Enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the two most common pathogens causing hand, foot, and mouth disease (HFMD). Previously, we obtained one candidate live attenuated strain each for EV-A71 and CV-A16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against EV-A71 and CV-A16 generated from these two candidate strains. Rhesus monkeys were intramuscularly treated with a live combinationvaccine against both EV-A71 and CV-A16 or with either vaccine alone. No fever or atypical clinical signs were observed in any animals. Monkeys vaccinated with the combinationlive vaccine presented no notable pathological changes in the brain, spinal cord, lung, and liver; in contrast, these regions showed inflammatory cell infiltration in monkeys treated with EV-A71 alone or CV-A16 alone. Weak viremia was detected in plasma after inoculation with the combinationvaccine; however, the duration of viral shedding in feces was increased. Biochemical studies revealed a slight increase in aspartate aminotransferase levels in monkeys inoculated with the live combination vaccine; however, histopathological findings did not attribute this change to liver damage. We also found that the live combinationvaccine induced a dual humoral immune response. Cytokine analysis indicated that the combined EV-A71/CV-A16 vaccine significantly down-regulated interleukin-8 production. Here, we have demonstrated that the live attenuated EV-A71/CV-A16 vaccine was safe and could trigger a dual specific immune response. However, its immune protection efficacy requires further investigation.

ABSTRACTCoxsackievirus A16 (CV-A16) is a major causative pathogen of hand, foot, and mouth diseases (HFMDs). The licensed HFMD vaccine targets EV-A71 without cross-protection against CV-A16. Thus, a CV-A16 vaccine is needed. In this study, the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate, K168-8Ac, were evaluated in a rhesus monkey model. Four passages of this strain (P35, P50, P60, and P70) were administered to monkeys, and its protective effect was identified. The immunized monkeys were clinically asymptomatic, except for slight fever. Weak viraemia was observed, and two doses of vaccination were found to significantly reduce virus shedding. High levels of antibody responses were observed (1:1024–1:2048), along with a significant increase in plasma IL-8. The I.M. group showed a much stronger humoural immunity. Pathological damage was detected mainly in lung tissues, although thalamus, spinal cord, lymph nodes, and livers were involved. After the viral challenge, it was found that two doses of vaccine reduced virus shedding, and the degree of lung damage and the number of organs involved decreased as the passage number increased. Overall, a robust immune response and partial protection against CV-A16, triggered by the K168-8Ac strain, were demonstrated. This study provides valuable data for CV-A16 vaccine development.

When the coils of wireless power transmission system based on a traditional topology is physically offset, the coupling coefficient between the coils will change significantly, which further leads to drastic changes in the output power of the system. This problem limits the application and promotion of wireless power transmission. In order to solve the problem of output power imbalance caused by coils' offset, this paper takes the wireless power transmission system of LCC-S type as an example, and proposes an optimization scheme for anti-offset performance based on the optimization design of compensation topology parameters. This scheme uses two freely adjustable variables K1 and K2 to optimize the design of the compensation network parameters of the wireless power transmission system, so that the system can automatically adjust the transmit current of the primary coil to maintain relatively stable output power. Finally, we build a 120W experimental prototype. When the lateral offset percentage δ of the coil is less than 35%, the maximum fluctuation rate of the output power of the system is kept within 10%, and the efficiency of the whole machine is kept above 81%.

Coxsackievirus A10 (CVA10) is the main pathogen of hand, foot, and mouth disease in China. However, there are no CVA10-specific drugs and vaccines, and the pathogenesis and effects of this virus in the body are unknown. We investigated the effect of a clinically isolated CVA10 virus strain (CVA10–25) to investigate its effect in suckling mice through different infection routes. We observed the dynamic distribution and proliferation of the virus in mouse tissues by infecting suckling mice with different doses of the virus and mice of different ages with the same dose of the virus. We also analysed the pathological characteristics after infection. A formaldehyde-inactivated experimental vaccine was prepared to immunise 5-week-old BALB/c female mice three times, and newborn suckling mice were tested for the presence of maternally transmitted antibodies. The viral load in each organ after intracerebral administration was higher than that after intraperitoneal administration; the peroral administration route did not cause disease in mice. Mouse paralysis and death after infection were related to age. The skeletal muscles, heart, and lung showed histopathological changes after infection. We established a 2-day-old BALB/c suckling mouse model that could be infected intracranially to study the pathogenesis and pathology of CVA10. Maternally transmitted antibodies protected the mice against the virus. This study provides a reference for CVA10-related pathogenesis and vaccine research.

Background: Hypertension is a leading contributor to the global burden of disease and to mortality. The combined effects of sleep factors on the risk of hypertension are unclear. We aimed to evaluate the effect of combined sleep factors on the risk of hypertension and to explore whether this association is independent of genetic risk.Methods: This population-based prospective cohort study included 170,378 participants from the UK Biobank study. We conducted a healthy sleep score based on a combination of major five sleep factors and a genetic risk score based on 118 risk variants. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: A total of 170,378 participants were included. Compared to participants with a healthy sleep score of 0–1, those with healthy sleep scores of 2 (HR, 0.90; 95% CI, 0.83–0.98), 3 (HR, 0.81; 95% CI, 0.75–0.88), 4 (HR, 0.74; 95% CI, 0.68–0.81), or 5 (HR, 0.67; 95% CI, 0.59–0.77) had increasingly lower risks of hypertension (P for trend

This report summarizes three “eyeless sight” experiments and reaffirms the authenticity of the phenomenon of clairvoyance (extrasensory perception). On 2014 and 2015, a total of 37 trials were conducted. Each trial involved a computer printing a 5-character permutation (e.g. 37K9J) in bold type on a piece of paper which was then folded to conceal the text. The “eyeless sight” practitioner was a girl who had previously been trained to develop her “eyeless sight” ability. The practitioner held the folded specimen between her thumb and forefinger. After adjusting to a specific state of consciousness (Second Consciousness State, SCS), the practitioner visualized a “ Third Eye Screen” (TES) in front of her forehead. The five-character string was then automatically perceived on the TES by the practitioner. After the perceived image stabilized, the permutation was reported to the researcher and transcribed. The whole experimental process was recorded on video cameras. The mean chance expectation for the correct hit rate of a five-character permutation is p≈10-70 and is vanishingly small. The importance of the SCS and the image generation process on the TES is discussed. Key words: Eyeless sight - Extrasensory perception (ESP) - Psychokinesis (PK) - Third Eye Screen (TES) - First Consciousness State (FCS) - Second Consciousness State (SCS) - recognition of characters with fingers (Clairvoyance)

Abstract Background Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan‐cancer has not been fully characterized. Methods Tissue or blood samples were subjected to next‐generation sequencing (NGS) for detection the IDH mutation. Results A total of 28.868 patients from more than 20 solid tumor species were analyzed. A total of 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer (BTC), 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer, and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. However, there were significant differences in IDH1 and IDH2 mutation frequency among different tumor species (p = 0.0003). Of the patients with IDH1 mutations, about 53.0% of these mutations occur in codons 132. Codons 172 (25.4%) was high‐frequency mutation subtypes in IDH2 mutation. TP53, PBRM1, and BAP1 were the most significantly mutated genes in BTC which were different from others cancer. Moreover, TMB were significantly higher in lung cancer, colorectal cancer, and gastric cancer than BTC (p = 0.0164, p

Volatility monitoring of a tiny amount of organic solvent, which reflects the profound understanding of the micro‐environmental chemical physics effect, plays a significant role in chemical reactions. Common approaches, such as microfluidic technology, undeniably encounter the issue of complicated fabrication or high cost, impeding their large‐scale application for monitoring the processes of chemical physics in micro‐reactions. Herein, a helical polymer film (HPF) molded by a cholesteric liquid crystal (CLC) is reported to record the helical arrangement. By infiltrating less than 1.0 μL volatile solvent into the HPF and monitoring the corresponding reflection spectral behaviors, an intrinsic dynamic chemical physics process, solvent properties, and molecular interactions between the solvent and the polymer network are quantitatively evaluated. Furthermore, to further explore the underlying interaction mechanism that results in spectral band shift, a dynamical model is established and elucidated, providing remarkable information and understanding of the dynamic chemical physics processes and interfacial molecular interactions between the solvent and the polymer. This work has tied a close bond among chemical engineering, photonics, and soft condensed physics, which can provide an avenue for the new field of application of LC photonics beyond display and optics.

Objective To examine the role of the long noncoding RNA LINC01296 in colorectal carcinoma (CRC) and to explore the underlying mechanism. Methods We detected LINC01296 expression levels in a cohort of 51 paired CRC and normal tissues. We also assessed the effects of LINC01296 on cell proliferation and apoptosis in CRC cells in vitro , and measured its effect on tumor growth in an in vivo mouse model. We identified the potential downstream targets of LINC01296 and assessed its regulatory effects. Results Expression levels of LINC01296 were elevated in 37/51 CRC tissues compared with the corresponding normal tissues and were significantly associated with tumor stage, lymph node metastasis, and distant metastasis. Knockdown of LINC01296 using antisense oligonucleotides inhibited cell proliferation and promoted apoptosis of colon cancer cells in vitro and inhibited tumor growth in vivo . Knockdown of LINC01296 also significantly increased the gene expression of p15 in colon cancer cells. LINC01296-specific suppression of p15 was validated by the interaction between enhancer of zeste homolog 2 and LINC01296. Conclusion Overexpression of LINC01296 suppressed the expression of p15 leading to CRC carcinogenesis. These findings may provide the basis for novel future CRC-targeted therapies.

This paper investigates an iterative learning control for single-input, single-output, and linear time-invariant discrete system. The special design of the learning gain matrix is introduced, where a finite uniform quantizer is incorporated with an encoding and decoding mechanism to realize the zero-error convergence of a tracking problem. Furthermore, the boundary-level calculation is considerably improved using lifting technique and infinity-norm of vectors under this mechanism. Some illustrations of the simulations verify the theoretical results.

A variable gain feedback PDα-type iterative learning control (ILC) update rate is proposed for the fractional-order nonlinear systems with time delay. The learning update rate combines the open-loop and closed-loop strategy, in which the system's current tracking error and the previous iterative control of the tracking error are simultaneously used to correct the control effect. So, the proposed method could both speed up the convergence rate along the iteration direction and reduce the tracking error along the time direction. Furthermore, the algorithm ensures that the system has good learning efficiency and control performance at the different running time and iterative batches due to the time-iteration-variable learning gain. The sufficient condition for the convergence of the proposed algorithm is analyzed. Finally, the validity of the proposed method is verified on a numerical example and a wind power generation system.

Epilepsy is one of the most common neurological disorders. Neuro-modulation becomes a promising way to address it. For an effective modulation, closed-loop mode is necessary but difficult. A control algorithm, which can adjust itself to get desired suppression of epileptic activity, is in great need. In this paper, active disturbance rejection control (ADRC) is utilized for its satisfied disturbance rejection and regulation performance. However, fixed observer parameters are difficult to fit the time-varying electrophysiological signals. Therefore, based on the estimation errors, an iterative learning approach is designed to get the parameters of an extended state observer (ESO). By combining the advantages of ADRC and the iterative learning, a learning type ADRC (LTADRC) is proposed to suppress the high amplitude epileptiform waves generated by the Jansen's neural mass model (NMM). For those variable parameters of an ESO, scalable bandwidths can be obtained to adapt to time-varying disturbance signals. It is of great significance for both ADRC and the neuro-modulation of epilepsy. Simulation results show that, compared with ADRC, much better performance can be obtained. It may provide a promising closed-loop regulation way for epilepsy in clinics.

This paper presents a novel off-line iterative learning control algorithm for multiple-input-multiple-output time-varying discrete stochastic systems. Using the steady-state Kalman filtering method, we provide a novel framework for the selection of optimal/sub-optimal fixed learning gain matrices in real applications, which is convenient for engineers. Meanwhile, this framework considerably decreases the calculation about the operations of inverting matrix by introducing a matrix Riccati equation at every iteration. It is strictly proved that the input error covariance converges to its steady-state value asymptotically in the mean square sense, and accordingly, the tracking error covariance also converges. The numerical simulations verify the theoretical results.

Context: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. Objective: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. Materials and methods: In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 μM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 106 BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. Results: The phenotypes and function of BMDMs showed that 5, 25 and 50 μM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1β, CD86 and MHCII in 25 μM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 μM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p

In this paper, we adopt D-type and PD-type learning laws with the initial state of iteration to achieve uniform tracking problem of multi-agent systems subjected to impulsive input. For the multi-agent system with impulse, we show that all agents are driven to achieve a given asymptotical consensus as the iteration number increases via the proposed learning laws if the virtual leader has a path to any follower agent. Finally, an example is illustrated to verify the effectiveness by tracking a continuous or piecewise continuous desired trajectory.

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1β), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1β/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

Background: Little is known about the role of dietary diversity changes in affecting cognitive function among older people. Therefore, we aimed to evaluate the associations between dietary diversity scores (DDS) changes with cognitive impairment among older adults in a large prospective cohort. Methods: Cognitive function was assessed using the Mini-Mental State Examination questionnaire at baseline and follow-up. A total of 9726 participants without Parkinson’s disease, dementia, or cognitive impairment were enrolled at baseline. Nine food groups were collected using simplified FFQ at baseline and follow-up surveys. Then nine food groups change patterns and DDS change patterns (overall, plant-based and animal-based) were assessed. The associations of above DDS changes patterns with subsequent cognitive impairment were evaluated. A multivariable-adjusted Cox proportional hazards model was used to estimate HRs and 95%CIs. Results: We documented 2805 cognitive impairments during 52,325 person-years of follow-up. Compared to high-to-high overall DDS change patterns, the multivariable adjusted HRs (95%CI) for high-to-medium, medium-to-medium, medium-to-low, low-to-medium and low-to-low DDS change patterns were 1.33 (1.12–1.57), 1.11 (0.94–1.32), 1.61 (1.39–1.86), 2.00 (1.66–2.40), 2.30 (1.90–2.78) and 2.80 (2.23–3.53), respectively. Compared with participants with stable DDS change pattern, those who in large improvement of DDS had a 13% lower risk of cognitive impairment (HRs, 0.87; 95%CI: 0.78–0.98). The associations of plant-based DDS, animal-based DDS, or nine food groups DDS change patterns with cognitive impairment were in a similar direction to the main result. Conclusions: Protective associations between maintaining high DDS and a reduced risk of cognitive impairment were observed. In contrast, lowering or maintaining a lower DDS increases the risk of cognitive impairment.

Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. Understanding workers' knowledge, attitudes, and practices (KAP) regarding this new infectious disease is crucial to preventing and controlling it. This study aimed to assess KAP regarding COVID-19 during the outbreak among workers in China. The present study was part of a cross-sectional online survey study conducted based on a large labor-intensive factory, which has 180,000 workers from various Chinese provinces, from 2 February 2020 to 7 February 2020. KAP related to COVID-19 were measured by 32 items, each item was measured with an agree/disagree/unclear format, and only correct responses were given 1 point. KAP regarding COVID-19 were measured with 20 items, 6 items and 6 items, respectively. A total of 123,768 valid responses (68.8%) were included in the analysis. Generally, the levels of knowledge (mean: 16.3 out of 20 points), attitudes (mean: 4.5 out of 6 points), and practices (mean: 5.8 out of 6 points) related to COVID-19 were high. Only 36,373 respondents (29.4%) disagreed that gargling with salt water is effective in protecting against COVID-19. Moreover, older respondents had decreased levels of knowledge and practices related to COVID-19 (both P values for the trend

In this paper, we discuss the consensus tracking problem by introducing two iterative learning control (ILC) protocols (namely, Dα-type and PDα-type) with initial state error for fractional-order homogenous and heterogenous multi-agent systems (MASs), respectively. The initial state of each agent is fixed at the same position away from the desired one for iterations. For both homogenous and heterogenous MASs, the Dα-type ILC rule is first designed and analyzed, and the asymptotical convergence property is carefully derived. Then, an additional P-type component is added to formulate a PDα-type ILC rule, which also guarantees the asymptotical consensus performance. Moreover, it turns out that the PDα-type ILC rule can further adjust the final performance. Two numerical examples are provided to verify the theoretical results.

Legionella pneumophila, an environmental bacterium that parasitizes protozoa, is the causative pathogen of Legionnaires' disease. L. pneumophila adopts a distinct biphasic life cycle that allows it to adapt to environmental conditions for survival, replication, and transmission. This cycle consists of a non-virulent replicative phase (RP) and a virulent transmissive phase (TP). Timely and fine-tuned expression of growth and virulence factors in a life cycle-dependent manner is crucial. Herein, we report evidence that CsrA, a key regulator of the switch between the RP and the TP, is dually regulated in a ClpP-dependent manner during the biphasic life cycle of L. pneumophila. First, we show that the protein level of CsrA is temporal during the life cycle and is degraded by ClpP during the TP. The ectopic expression of CsrA in a ΔclpP mutant, but not in the wild type, inhibits both the initiation of the RP in vitro and the invasiveness to Acanthamoeba castellanii, indicating that the ClpP-mediated proteolytic pathway regulates the CsrA protein level. We further show that the temporally expressed IHFB is the transcriptional inhibitor of csrA and is degraded via a ClpP-dependent manner during the RP. During the RP, the level of CsrA is increased by promoting the degradation of IHFB and reducing the degradation of the accumulated CsrA via a ClpP-dependent manner. During the TP, the level of CsrA is decreased by inhibiting the degradation of IHFB and promoting the degradation of the accumulated CsrA via a ClpP-dependent manner as well. In conclusion, our results show that the growth-stage-specific expression level of CsrA is dually regulated by ClpP-dependent proteolysis at both the transcription and protein levels during the biphasic life cycle of L. pneumophila.

Magnetotransport measurements of PtPb _4 single crystals with the T _c of ∼2.80 K reveal pronounced exotic topological nature. An anomalous negative longitudinal magnetoresistance (MR) related to the chiral anomaly and a linear-like transverse MR examined within the framework of quantum MR theory were studied. Results indicate the presence of chiral-anomaly-induced quantum transport associated with the Weyl states and show a Dirac-cone-like band dispersion in PtPb _4 . This work reveals the drastic impact of the concept that the surface electrons in a Weyl fermion state may dominate the normal-state magnetotransport in PtPb _4 , leading to the conclusion that PtPb _4 can be a Weyl-semimetal superconductor candidate.

Aromatase inhibitors are used to treat oestrogen-receptor-positive breast cancer. Here, the authors use genomic approaches to analyse tumours before and after neo-adjuvant treatment and find that treatment alters the clonal landscape of the tumours.