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Abstract Breast cancer is a common malignant tumor, which mostly occurs in female population and is caused by excessive proliferation of breast epithelial cells. Breast cancer can cause nipple discharge, breast lumps and other symptoms, but these symptoms lack certain specificity and are easily confused with other diseases, thus affecting the early treatment of the disease. Once the tumor progresses to the advanced stage, distant metastasis can occur, leading to dysfunction of the affected organs, and even threatening the patients’ lives. In this study, we synthesized high drug-loading gel particles and applied them to control the release of insoluble drugs. This method is simple to prepare, cost-effective, and validates their potential in breast cancer therapy. We first characterized the morphology and physicochemical properties of gel loaded with newly synthesized compound 1 by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA). Using newly synthesized insoluble compound 1 as a model drug, its efficacy in treating breast cancer was investigated. The results showed that hydrogel@compound 1 was able to significantly inhibit the proliferation, migration and invasion of breast cancer cells. Additionally, we utilized machine learning to screen three structurally similar compounds, which showed promising therapeutic effects, providing a new approach for the development of novel small-molecule drugs.

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

BackgroundDespite China's economic growth, rural living environments have often lagged behind. While public participation is gaining importance in environmental governance, the magnitude and mechanism of its impact remain understudied.PurposeThis research investigates the relationship between public environmental concerns and the rural living environment in China and explores how public concerns impact living conditions.MethodologyUsing panel data from 245 prefecture-level cities (2012–2021), we employed the entropy method to measure rural living environment scores and used fixed-effect models to analyze the relationship between public concern and the living environment.ResultsThe findings demonstrate a positive relationship between strong public environmental concerns and improved rural living environments. Further analysis suggests that local government environmental attention acts as a partial mediator in this relationship.ConclusionThis study reveals that public participation can influence government policies, ultimately leading to positive environmental outcomes. Promoting public participation in environmental governance is crucial for improving the rural living environment.

This systematic study on the international research trends in carbon neutrality underscores its critical role in combating global warming and advancing sustainable development. By leveraging the “Web of Science Core Collection” databases and employing CiteSpace software for visual analysis, we examined 2223 research papers to track the influence and trends of key countries, institutions, and authors. Our results reveal a significant increase in publication volume, indicating a robust development potential for carbon neutrality research. The study also identifies environmental science, environmental research, and energy and fuel science as central interdisciplinary hubs, highlighting the importance of cross-disciplinary collaboration. Notably, China leads in publication output but has room for improvement in citation impact, suggesting a need for enhanced research quality and international visibility. The study's findings are instrumental for guiding future research directions, policy-making, and interdisciplinary cooperation, particularly in the fields of environmental science and energy, to accelerate progress towards carbon neutrality and global climate governance.

PurposeThe aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy.MethodsThe PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve.ResultsThe results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist–guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist–guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist–guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery.ConclusionIn general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.

Abstract Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple‐negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC‐CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC‐CR cells with TRAF6 knocked down regained significantly TRAF6‐dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2‐mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

Abstract Background Electronic medical records (EMRs) contain a wealth of information related to breast cancer diagnosis and treatment. Extracting relevant features from these medical records and constructing a knowledge graph can significantly contribute to an efficient data analysis and decision support system for breast cancer diagnosis. Methods An approach was proposed to develop a workflow for effectively extracting breast cancer-related features from Chinese breast cancer mammography reports and constructing a knowledge graph for breast cancer diagnosis. Firstly, the concept layer of the knowledge graph for breast cancer diagnosis was constructed based on breast cancer diagnosis and treatment guidelines, along with insights from clinical experts. .Next, a BiLSTM-Highway-CRF model was designed to extract the mammography features, which formed the data layer of the knowledge graph. Finally, the knowledge graph was constructed by combining the concept layer and the data layer in a Neo4j graph data platform, and then applied in visualization analysis, semantic query and computer assisted diagnosis. Results Mammographic features were extracted from a total of 1171 mammography examination reports. The overall extraction performance of the model achieved an accuracy rate of 97.16%, a recall rate of 98.06%, and a F1 score of 97.61%. Additionally, 47,660 relationships between entities were identified based on the four different types of relationships defined in the concept layer. The knowledge graph for breast cancer diagnosis was constructed after inputting mammographic features and relationships into the Neo4j graph data platform. The model was assessed from the concept layer, data layer, and application layer perspectives, and showed promising results. Conclusions The proposed workflow is applicable for constructing knowledge graphs for breast cancer diagnosis based on Chinese EMRs. This study serves as a reference for the rapid design, construction, and application of knowledge graphs for diagnosis and treatment of other diseases. Furthermore, it offers a potential solution to address the issues of limited data sharing and format inconsistencies present in Chinese EMR data.

The multilayer graphene (MLG) reinforced WC-10Ni3Al cemented carbide was prepared by microwave sintering. The effects of the sintering temperature and MLG content on the microstructure and mechanical properties of the WC-10Ni3Al cemented carbide were investigated. The promotion effect and strengthening mechanism of MLG on WC-10Ni3Al by microwave sintering were explored. The tribological properties of WC-10Ni3Al and Ti6Al4V(TC4) were studied, and the wear mechanism of WC-10Ni3Al was revealed. The experiment result show that the WC-10Ni3Al-0.5 wt.% MLG sample sintered at 1450 °C had its greatest mechanical properties with a relative density of 96.9%, hardness of 1430 HV, flexural strength of 1410 MPa and fracture toughness of 15.7 MPa mm1/2, which were 4.2%, 12.2%, 24.4%, and 29.6% greater than those of the sample without MLG added, respectively. The reinforcing and toughening mechanisms of adding MLG in WC-10Ni3Al samples consist of fine crystal strengthening, crack bridging and deflection, MLG pulling out and bridging. The results of friction experiment show that the friction coefficient and wear rate of the WC-10Ni3Al samples were lower than those of YG8 (WC-8 wt. % Co cemented carbide). The WC-10 Ni3Al-0.5 wt.% MLG sample obtained the lowest friction coefficient of 0.35 and the lowest wear rate of 1.69 × 10−5 mm3N−1m−1. A stable solid lubrication film was produced on the friction surface of the WC-10Ni3Al samples, which was conducive to reducing the breakage and wear of WC grains. MLG can enhance the stability of solid lubrication film and reduce its friction coefficient.

Prostate cancer is a common malignancy in urology which often develops into castration-resistant prostate cancer (CRPC) after hormone therapy. Studies have shown that the mechanism of its occurrence is related to androgen receptor splice variants (AR splice variants). This work employs a bibliometric approach to explore the knowledge structure and emerging trends of AR variants in prostate cancer. The literature from 2000 to 2021 was obtained from Web of Science Core Collection (WoSCC), and the results were analyzed and visualized via CiteSpace and VOSviewer regarding publication number, citation number, country, region, institution, journal, author, keyword and reference. A total of 1503 publications were obtained. The number of publications and citations in this field is increasing. United States is the most prominent country, and University of Washington is the most influential institution in terms of this research field. European Urology is the most authoritative journal regarding this field. Gleave, Martin is the most productive author, and collaborated closely with others having centrality >0.1. The keywords abiraterone and AR-V7 have the strongest citation bursts in recent years and continuing to the end of 2021 which indicate the trend and further research directions. The most cited papers and co-cited references were related to the clinical significance of AR-V7 and its mechanism of promoting CRPC. This study used visualization software CiteSpace and VOSviewer to analyze the current status and the research trends of AR variants in prostate cancer (PCa) over the past 20 years. The findings can identify research hotspots and reveal future research directions.

BackgroundRecent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and duodenal ulcer (DU). However, the causal connection remains unsure.MethodsA two-sample Mendelian randomization (MR) is carried out to explore the connection between the GM and DU or GU. Data on the GM comes from the MiBioGend database, and GU or DU data are based on the FinnGen database. One group of single nucleotide polymorphisms (SNPs) (P < 5 × 10−8) are served as instrumental variables (IVs). To obtain a more comprehensive conclusion, the other SNPs (P < 1 × 10−5) are selected as IVs. Inverse variance weighting (IVW) is used to determine the causal relationship.ResultsAt the level of P < 1 × 10−5, the IVW analysis suggests that Clostridiaceae1, Butyriccoccus, and Peptcoccus have harmful effects on GU, while LachnospiraceaeUCG004 and MollicutesRF9 have beneficial effects on GU. Then, in the case of DU, the IVW analysis suggested that Lentisphaeria, Negativicutes, Clostridiaceae1, ClostridiumseMnsustricto1, ErysipelotrichaceaeUCG003, LachnospiraceaeNC2004group, Selenomonadale, Victivallales, and Lentisphaerae have harmful effects, while Catenibacterium, Escherichia.Shigella, LachnospiraceaeUCG008, and Sutterella have beneficial effects. When P < 5 × 10−8, IVW analysis suggests that GM has no significant influence on GU or DU.ConclusionThis two-sample MR indicates a causal relationship between GM and GU or DU.

The regrowth and subsequent exposure of opportunistic pathogens (OPs) whilst reopening buildings that have been locked down due to the stay-at-home restrictions to limit the spread of COVID-19, is a public health concern. To better understand such microbiological risks due to lowered occupancy and water demand in buildings, first and post-flush water samples (n = 48) were sampled from 24 drinking water outlets from eight university buildings in two campuses (urban and rural), with various end-user occupancies. Both campuses were served with chlorinated water originating from a single drinking water distribution system in South-East Queensland, situated 14 km apart, where the rural campus had lower chlorine residuals. Culture-dependent and culture-independent methods (such as flow cytometry, qPCR and 16S rRNA gene amplicon sequencing) were used concurrently to comprehensively characterise the OPs of interest (Legionella spp., Pseudomonas aeruginosa, and nontuberculous mycobacteria (NTM)) and the premise plumbing microbiome. Results showed that buildings with extended levels of stagnation had higher and diverse levels of microbial growth, as observed in taxonomic structure and composition of the microbial communities. NTM were ubiquitous in all the outlets sampled, regardless of campus or end-user occupancy of the buildings. qPCR and culture demonstrated prevalent and higher concentrations of NTM in buildings (averaging 3.25 log10[estimated genomic copies/mL]) with extended stagnation in the urban campus. Furthermore, flushing the outlets for 30 minutes restored residual and total chlorine, and subsequently decreased the levels of Legionella by a reduction of 1 log. However, this approach was insufficient to restore total and residual chlorine levels for the outlets in the rural campus, where both Legionella and NTM levels detected by qPCR remained unchanged, regardless of building occupancy. Our findings highlight that regular monitoring of operational parameters such as residual chlorine levels, and the implementation of water risk management plans are important for non-healthcare public buildings, as the levels of OPs in these environments are typically not assessed.

Methods Cross-sectional data on 36 621 men (n=15 719) and women (n=20,902) aged 65 years or higher were obtained from the ninth round of the Survey of Health, Ageing and Retirement in Europe. The outcomes were measured by psychosocial well-being reflected with self-reported depression, nervousness, loneliness and sleep disturbances. Social support was measured in terms of receiving help from own children, relatives and neighbours/friends/colleagues since the pandemic outbreak.Result About one-third of the participants reported depression (31.03%), nervousness (32.85%), loneliness (32.23%) and sleep trouble (33.01%). The results of multivariable regression analysis revealed that social support was a protective factor to psychological well-being. For instance, receiving help from own children (RD=−0.13, 95% CI=−0.14 to –0.12), relatives (RD=−0.08, 95% CI=−0.11 to –0.06), neighbours/friends/colleagues (RD=−0.11, 95% CI=−0.13 to –0.09) and receiving home care (RD=−0.20, 95% CI=−0.22 to –0.18) showed significantly lower risk difference for depression. Similar findings were noted for loneliness, nervousness, and sleep trouble as well, with the risk difference being slightly different for men and women in the gender-stratified analysis. For instance, the risk difference in depression for receiving help from own children was −0.10 (95% CI=−0.12 to –0.08) among men compared with −0.12 (95% CI=−0.14 to –0.11) among women. The risk differences in the outcome measures were calculated using generalised linear model for binomial family.Conclusion Findings of the present study highlight a protective role of social support on psychological well-being among both men and women. Developing strategies to promote social support, especially among older adults, may mitigate the rising burden of psychological illness during the COVID-19 pandemic.

BackgroundUndifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue sarcoma with a poor prognosis and no clear effective clinical means for treatment, and there has been no significant progress in research within this field in recent years. This study aimed to investigate the epidemiology, etiology, clinical features, diagnostic modalities, various treatment modalities, and prognosis of retroperitoneal undifferentiated pleomorphic sarcoma and to contribute to the clinical management of this type of disease. In this study, we report a case of undifferentiated pleomorphic sarcoma with a primary origin in the retroperitoneum. Undifferentiated pleomorphic sarcoma occurring in the retroperitoneum is rarely reported.Case descriptionA 59-year-old man with abdominal distension and pain for 4 months presented to our hospital after the failure of conservative treatment. A 9.6 cm by 7.4 cm mass in the left retroperitoneum was found on a CT scan of the whole abdomen with three degrees of enhancement. After surgical treatment, the tumor and the left kidney were completely removed, and pathological examination and genetic sequencing showed an apparent undifferentiated pleomorphic sarcoma. The patient subsequently declined follow-up treatment and is currently alive and well.ConclusionsAt the current level of clinical technology, the treatment of undifferentiated pleomorphic sarcoma is still in the exploratory stage, and the scarcity of clinical cases of this disease may have hindered the acquisition of clinical trials and research data for this disease. At present, the first choice of treatment for undifferentiated pleomorphic sarcoma is still radical resection. In the existing clinical studies, there are no strong data to support the effect of preoperative neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy in clinical practice. Similar to other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential treatment for this disease in the future. Targeted therapy for this disease still needs further exploration, and we need more reports on related diseases to promote future treatment and research on this disease.

ObjectiveTo understand the pathogenic spectrum and epidemiological characteristics of severe acute respiratory infection （SARI） in adult inpatients in Yangpu District， Shanghai， China， in order to explore strategies for the prevention and treatment of respiratory infectious diseases.MethodsIndividual cases were from adult inpatients with SARI in Yangpu District， Shanghai， China from January 2019 to July 2021. Their respiratory samples were collected for etiological pathogen testing.ResultsA total of 681 SARI cases were enrolled for sampling and lab testing. Among them， 79.00% were aged 60 years and older， and 75.48% had confirmed chronic disease history. A total of 163 infection inpatients （23.94%） were positive for at least one pathogen. The pathogens identified most frequently were influenza A virus （6.75%）， followed by rhinovirus/enterovirus （3.23%）， parainfluenza virus （PIV） （2.79%）， Mycoplasma pneumoniae （2.35%）， coronavirus （CoV） （2.06%）. The positive rates of adenovirus （AdV）， human metapneumovirus （hMPV）， respiratory syncytial virus and bocavirus were all less than 2%. Bacterial strains were identified in eleven SARI cases， including Staphylococcus aureus and Pseudomonas aeruginosa （4 strains）， Klebsiella pneumoniae （3 strains）. Legionella pneumophila was detected in 9 cases （1.32%） and Bordetella pertussis in 5 cases （0.73%）. Two pathogens were co-detected from 11 cases， accounting for 1.62% of 163 positive cases. The most common co-detected pathogens were influenza A virus and other pathogens， accounting for 54.55% of the mixed infection. The positive rates of pathogens were not significantly different between less than 60 years old and over 60 years old groups except for Bordetella pertussis， adenovirus and Mycoplasma pneumonia（P

Abstract Background Horizontal gene transfer (HGT) plays a critical role in the spread of antibiotic resistance and the evolutionary shaping of bacterial communities. Conjugation is the most well characterized pathway for the spread of antibiotic resistance, compared to transformation and transduction. While antibiotics have been found to induce HGT, it remains unknown whether non-antibiotic pharmaceuticals can facilitate conjugation at a microbial community-wide level. Results In this study, we demonstrate that several commonly consumed non-antibiotic pharmaceuticals (including carbamazepine, ibuprofen, naproxen and propranolol), at environmentally relevant concentrations (0.5 mg/L), can promote the conjugative transfer of IncP1-α plasmid-borne antibiotic resistance across entire microbial communities. The over-generation of reactive oxygen species in response to these non-antibiotic pharmaceuticals may contribute to the enhanced conjugation ratios. Cell sorting and 16S rRNA gene amplicon sequencing analyses indicated that non-antibiotic pharmaceuticals modulate transconjugant microbial communities at both phylum and genus levels. Moreover, microbial uptake ability of the IncP1-α plasmid was also upregulated under non-antibiotic pharmaceutical exposure. Several opportunistic pathogens, such as Acinetobacter and Legionella, were more likely to acquire the plasmid conferring multidrug resistance. Conclusions Considering the high possibility of co-occurrence of pathogenic bacteria, conjugative IncP1-α plasmids and non-antibiotic pharmaceuticals in various environments (e.g., activated sludge systems), our findings illustrate the potential risk associated with increased dissemination of antibiotic resistance promoted by non-antibiotic pharmaceuticals in complex environmental settings. Video abstract

The ultrafast modulation of terahertz (THz) waves is essential for numerous applications, such as high-rate wireless communication, nonreciprocal transmission, and linear frequency conversion. However, high-speed THz devices are rare due to the lack of materials that rapidly respond to external stimuli. Here, we demonstrate a dynamic THz metasurface by introducing an ultrathin superconducting microbridge into metallic resonators to form a superconductor-metal hybrid structure. Exploiting the susceptibility of superconducting films to external optical and THz pumps, we realized resonance mode switching within a few picoseconds. The maximum on/off ratio achieved is 11 dB. The observed periodic oscillation of transmission spectra both in the time and frequency domain under intense THz pump pulse excitation reveals the excitation of Higgs amplitude mode, which is used to realize picosecond scale THz modulation. This study opens the door to ultrafast manipulation of THz waves using collective modes of condensates, and highlights an avenue for developing agile THz modulation devices.

Abstract The development of antibiotic resistance as an unavoidable consequence of the application of antimicrobials is a significant concern for human health. Antidepressants are being increasingly consumed globally. Human gut microbial communities are frequently exposed to antidepressants, yet little is known about the interaction between antidepressants and antibiotic resistance. This study aimed to investigate whether antidepressants can accelerate the dissemination of antibiotic resistance by increasing the rate of the horizontal transfer of antibiotic resistance genes (ARGs). Results demonstrated that some of the commonly-prescribed antidepressants (Duloxetine, Sertraline, Fluoxetine and Bupropion) at clinically relevant concentrations can significantly (n = 9; p adj

ObjectiveTo analyze the characteristics and trends of notifiable infectious diseases in Yangpu District of Shanghai， from 1950 to 2020， and to provide scientific basis for the formulation of control measures.MethodsDescriptive epidemiological method was used to collect and analyze the epidemiological data of notifiable infectious diseases.ResultsA total of 1 186 675 cases from 38 types of infectious diseases were reported. The annual morbidity of Class A and Class B infectious diseases fluctuated between 138.22/105 and 7 861.45/105， showing a decreasing trend. Among the 3 785 cases of death， the top five were measles， viral hepatitis， dysentery， tuberculosis and epidemic cerebrospinal meningitis. The high incidence diseases were intestinal infectious diseases， and the respiratory infectious diseases fluctuated in a wide range. Furthermore， blood-borne infectious diseases and sexual -transmitted diseases had continued to increase in recent years. As the result of normative vaccination， the incidence of associated infectious disease showed a downward trend.ConclusionThe incidence of infectious diseases in Yangpu District was on the drop from 1950 to 2020. Prevention and control work should focus on respiratory infectious diseases， blood-borne infectious diseases and sexual -transmitted diseases in the future. Furthermore， it is important to guarantee normative vaccination， especially， for prevention and control of infectious diseases.

Abstract Background Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects. Results Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~ 70%) and EE (~ 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications. Conclusions This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment. Graphical Abstract

Purpose: To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC).Methods: Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared.Results: Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48–0.67) and rPFS (HR: 0.33, 95% CrI:0.26–0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44–0.75) and rPFS(HR, 0.29; 95% CrI: 0.23–0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38–0.72) and rPFS (HR, 0.28; 95% CrI:0.21–0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44–0.77; rPFS: HR, 0.44; 95% CrI:0.33–0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58–0.80) and rPFS (HR:0.37, 95% CrI:0.25–0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35–0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15–0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31–3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01–8.18) and fatigue (OR, 0.96; 95% CrI:0.63–1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs.Conclusion: Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.

Abstract Background Juvenile xanthogranuloma (JXG) is a kind of non-Langerhans cell histiocytosis, usually with skin lesions as the main manifestation. It rarely occurs in other tissues or organs and even more rarely is it found in the skull. Here, we report a case of xanthogranuloma derived from the temporal bone that was not present in any other parts of the body. Case presentation A 15-year-old boy had an unaccountable right migraine for 7 months. A mass with tenderness was located behind his right ear. The mass gradually increased in size, and his headache continued. Eventually, he came to our hospital for treatment. A computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a cystic solid mass in the right temporo-occipital region with skull destruction. The clinical diagnosis was haemangiopericytoma and skull-derived tumour. Haematological and biochemical results were as follows: alanine aminotransferase (ALT) 7 U/L; aspartate aminotransferase (AST) 12 U/L; basophil percentage (BASO%) 1.2%; normal coagulation. The patient was successfully treated with total surgical resection of the tumour. Postoperative histopathology examination showed xanthogranuloma, and his prognosis after surgery was good. Conclusions Because JXG rarely occurs in the skull and lacks typical imaging findings, an accurate diagnosis is difficult. The diagnosis of this disease mainly depends on pathological examination and immunohistochemistry. If feasible, many intracranial lesions can be cured through complete resection.

A metal- and aldehyde-free visible-light-driven photoredox-neutral alkene acylarylation with readily available cyanoarenes is described. A variety of 3-(arylmethyl)chroman-4-ones (i.e., homoisoflavonoids) and analogs are efficiently synthesized with good functional group tolerance. This mild protocol relies on a phosphoranyl radical-mediated acyl radical-initiated cyclization and selective radical-radical coupling sequence, and is also further highlighted by subsequent derivatization to chromone and 2H-chromene as well as its application in the three-component alkene acylarylation.

Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC).Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated.Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57–0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59–0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39–0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30–0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68–12.63; OR: 1.07, 95% CrI: 0.03–36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15–2.11).Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.

PurposePSA is currently the most commonly used screening indicator for prostate cancer. However, it has limited specificity for the diagnosis of prostate cancer. We aim to construct machine learning-based models and enhance the prediction of prostate cancer.MethodsThe data of 551 patients who underwent prostate biopsy were retrospectively retrieved and divided into training and test datasets in a 3:1 ratio. We constructed five PCa prediction models with four supervised machine learning algorithms, including tPSA univariate logistic regression (LR), multivariate LR, decision tree (DT), random forest (RF), and support vector machine (SVM). The five prediction models were compared based on model performance metrics, such as the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, calibration curve, and clinical decision curve analysis (DCA).ResultsAll five models had good calibration in the training dataset. In the training dataset, the RF, DT, and multivariate LR models showed better discrimination, with AUCs of 1.0, 0.922 and 0.91, respectively, than the tPSA univariate LR and SVM models. In the test dataset, the multivariate LR model exhibited the best discrimination (AUC=0.918). The multivariate LR model and SVM model had better extrapolation and generalizability, with little change in performance between the training and test datasets. Compared with the DCA curves of the tPSA LR model, the other four models exhibited better net clinical benefits.ConclusionThe results of the current retrospective study suggest that machine learning techniques can predict prostate cancer with significantly better AUC, accuracy, and net clinical benefits.

Abstract Background Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. Results To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells. Conclusions A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.

The ATP binding cassette transporter ABCG2 is a physiologically important drug transporter that has a central role in determining the ADMET (absorption, distribution, metabolism, elimination, and toxicity) profile of therapeutics, and contributes to multidrug resistance. Thus, development of predictive in silico models for the identification of ABCG2 inhibitors is of great interest in the early stage of drug discovery. In this work, by exploiting a large public dataset, a number of ligand-based classification models were developed using partial least squares-discriminant analysis (PLS-DA) with molecular interaction field- and fingerprint-based structural description methods, regarding physicochemical and fragmental properties related to ABCG2 inhibition. An in-house dataset compiled from recently experimental studies was used to rigorously validated the model performance. The key molecular properties and fragments favored to inhibitor binding were discussed in detail, which was further explored by docking simulations. A highly informative chemical property was identified as the principal determinant of ABCG2 inhibition, which was utilized to derive a simple rule that had a strong capability for differentiating inhibitors from non-inhibitors. Furthermore, the incorporation of the rule into the best PLS-DA model significantly improved the classification performance, particularly achieving a high prediction accuracy on the independent in-house set. The integrative model is simple and accurate, which could be applied to the evaluation of drug-transporter interactions in drug development. Also, the dominant molecular features derived from the models may help medicinal chemists in the molecular design of novel inhibitors to circumvent ABCG2-mediated drug resistance.

Autonomy increases the ability of earth observing satellites by allowing them to acquire more images. This is enabled by an efficient planning and scheduling algorithm which is able to make quick decisions onboard. Due to the NP-hardness of the agile earth observing satellite (AEOS) onboard scheduling problem, heuristic and metaheuristic algorithms seem to be appropriate to cope with increasingly enlarged problems. Also, the algorithms need to be intelligent enough to deal with dynamically changing situations onboard. Such algorithms are missing in the literature and we make the first attempt to propose a learning-based approach (LBA) for the AEOS onboard scheduling problem. LBA adopts an offline training - onboard scheduling paradigm where it trains a classifier using massive historical data offline on the ground and embeds this classifier to an onboard greedy construction algorithm. At each construction step, the greedy algorithm uses the classifier to test the potential of a task and arranges its observation time if it is accepted by the classifier. Extensive experimental results show that the proposed LBA is highly suitable for onboard use in terms of both solution quality and response time. In particular, LBA easily dominates state-of-the-art algorithms by producing very high quality solutions for large-size problems (with over 100 tasks) in seconds.

Background: Thousands of gene fusions have been reported in prostate cancer, but their authenticity, incidence, and tumor specificity have not been thoroughly evaluated, nor have their genomic characteristics been carefully explored. Methods: We developed FusionVet to dedicatedly validate known fusion genes using RNA-seq alignments. Using FusionVet, we re-assessed 2727 gene fusions reported from 36 studies using the RNA-seq data generated by The Cancer Genome Atlas (TCGA). We also explored their genomic characteristics and interrogated the transcriptomic and DNA methylomic consequences of the E26 transformation-specific (ETS) fusions. Results: We found that nearly two-thirds of reported fusions are intra-chromosomal, and 80% of them were formed between 2 protein-coding genes. Although most (76%) genes were fused to only 1 partner, we observed many fusion hub genes that have multiple fusion partners, including ETS family genes, androgen receptor signaling pathway genes, tumor suppressor genes, and proto-oncogenes. More than 90% of the reported fusions cannot be validated by TCGA RNA-seq data. For those fusions that can be validated, 5% were detected from tumor and normal samples with similar frequencies, and only 4% (120 fusions) were tumor-specific. The occurrences of ERG, ETV1 , and ETV4 fusions were mutually exclusive, and their fusion statuses were tightly associated with overexpressions. Besides, we found ERG fusions were significantly co-occurred with PTEN deletion but mutually exclusive with common genomic alterations such as SPOP mutation and FOXA1 mutation. Conclusions: Most of the reported fusion genes cannot be validated by TCGA samples. The ETS family and androgen response genes were significantly enriched in prostate cancer–specific fusion genes. Transcription activity was significantly repressed, and the DNA methylation was significantly increased in samples carrying ERG fusion.

The spread of antibiotic resistance has become a major concern for public health. As emerging contaminants, various metallic nanoparticles (NPs) and ionic heavy metals have been ubiquitously detected in various environments. Although previous studies have indicated NPs and ionic heavy metals could exhibit co-selection effects for antibiotic resistance, little is known about whether and how they could promote antibiotic resistance spread via horizontal gene transfer across bacterial genera. This study, we report both CuO NPs and copper ions (Cu2+) could stimulate the conjugative transfer of multiple-drug resistance genes. When exposing bacteria to CuO NPs or Cu2+ at environmental-relevant and sub-inhibitory concentrations (e.g., 1–100 μmol/L), conjugation frequencies of plasmid-encoded antibiotic resistance genes across genera (i.e., from Escherichia coli to Pseudomonas putida) were significantly enhanced (p

The widespread use of CuO nanoparticles (NPs) results in their continuous release into the environment, which could pose risks to public health and to microbial ecosystems. Following consumption, NPs will initially enter into sewer systems and interact with and potentially influence sewer microbial communities. An understanding of the response of microbes in sewers, particularly sulfate-reducing bacteria (SRB), to the CuO NPs induced stress is important as hydrogen sulfide produced by SRB can cause sewer corrosion and odour emissions. In this study, we elucidated how the anabolic and catabolic processes of a model SRB, Desulfovibrio vulgaris Hidenborough (D. vulgaris), respond to CuO NPs. Physiological analyses indicated that the exposure of the culture to CuO NPs at elevated concentrations (>50 mg/L) inhibited both its anabolic and catabolic activities, as revealed by lowered cell proliferation and sulfate reduction rate. The antibacterial effects of CuO NPs were mainly attributed to the overproduction of reactive oxygen species. Transcriptomic analysis indicated that genes encoding for flagellar assembly and some genes involved in electron transfer and respiration were down-regulated, while genes for the ferric uptake regulator (Fur) were up-regulated. Moreover, the CuO NPs exposure significantly up-regulated genes involved in protein synthesis and ATP synthesis. These results suggest that CuO NPs inhibited energy conversion, cell mobility, and iron starvation to D. vulgaris. Meanwhile, D. vulgaris attempted to respond to the stress of CuO NPs by increasing protein and ATP synthesis. These findings offer new insights into the bacterial-nanoparticles interaction at the transcriptional level, and advance our understanding of impacts of CuO NPs on SRB in the environment. Keywords: CuO nanoparticles, Ecotoxicity, Sulfate-reducing bacteria, Genome-wide RNA sequencing

Background: Antibiotic resistance poses an increasing threat to public health. Horizontal gene transfer (HGT) promoted by antibiotics is recognized as a significant pathway to disseminate antibiotic resistance genes (ARGs). However, it is unclear whether non-antibiotic, anti-microbial (NAAM) chemicals can directly promote HGT of ARGs in the environment. Objectives: We aimed to investigate whether triclosan (TCS), a widely-used NAAM chemical in personal care products, is able to stimulate the conjugative transfer of antibiotic multi-resistance genes carried by plasmid within and across bacterial genera. Methods: We established two model mating systems, to investigate intra-genera transfer and inter-genera transfer. Escherichia coli K-12 LE392 carrying IncP-α plasmid RP4 was used as the donor, and E. coli K-12 MG1655 or Pseudomonas putida KT2440 were the intra- and inter-genera recipients, respectively. The mechanisms of the HGT promoted by TCS were unveiled by detecting oxidative stress and cell membrane permeability, in combination with Nanopore sequencing, genome-wide RNA sequencing and proteomic analyses. Results: Exposure of the bacteria to environmentally relevant concentrations of TCS (from 0.02 μg/L to 20 μg/L) significantly stimulated the conjugative transfer of plasmid-encoded multi-resistance genes within and across genera. The TCS exposure promoted ROS generation and damaged bacterial membrane, and caused increased expression of the SOS response regulatory genes umuC, dinB and dinD in the donor. In addition, higher expression levels of ATP synthesis encoding genes in E. coli and P. putida were found with increased TCS dosage. Conclusions: TCS could enhance the conjugative ARGs transfer between bacteria by triggering ROS overproduction at environmentally relevant concentrations. These findings improve our awareness of the hidden risks of NAAM chemicals on the spread of antibiotic resistance. Keywords: Non-antibiotic antimicrobial (NAAM), Triclosan, Environmental concentration, Antibiotic resistance genes, Horizontal gene transfer

Earth observation satellites (EOSs) are taking a large number of pictures with increasing resolution which produce massive image data. Satellite data transmission becomes the bottleneck part in the process of EOS resource management. In this paper, we study the earth observation satellite integrated scheduling problem (EOSIS) where the imaging activities and download activities are considered integratively. We propose an integer linear programming model to formulate the problem. Due to the NP-hardness of the problem, we propose an efficient local search heuristic (ELSH) to solve problems of large size. ELSH uses a dedicated local search method to guarantee algorithm performance and efficient constraint handling mechanisms to guarantee algorithm efficiency. Numerical experimental results show that the algorithm demonstrates excellent performance on a set of benchmark instances. The ELSH achieves optimal results for all small-size instances (with 50 targets, two satellites, and three ground stations), and is very robust for large instances with up to 2000 targets. Moreover, the proposed ELSH easily dominates the state-of-the-art algorithm.

SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced G0/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDB1 which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.

Opportunistic network coding (ONC) based broadcast transmission algorithms were proposed to improve the transmission efficiency for wireless single-hop networks.Based on the traditional wireless broadcast transmission model,ONC based solo combination packet broadcast transmission (ONCSB) algorithm and ONC based multiple combination packets broadcast transmission (ONCMB) algorithm were osed respectively.By employing the method of combination different lost packets with different strategies,the ONCSB and ONCMB can improve the throughput with recovering lost packets via a combination packet efficiently.The simulation results show that either ONCSB or ONCMB can lead to better transmission bandwidth performance compared with other algorithms under different wireless channel conditions.

INTRODUCTION:A consistent eating style might be beneficial to avoid overeating in a food-rich environment. Eating consistency entails maintaining a similar dietary pattern across different eating situations. This construct is relatively under-studied, but the available evidence suggests that eating consistency supports successful weight maintenance and decreases risk for metabolic syndrome and cardiovascular disease. Yet, personality and situation predictors of consistency have not been studied. METHODS:A community-based sample of 164 women completed various personality tests, and 139 of them also reported their eating behaviour 6 times/day over 10 observational days. We focused on observations with meals (breakfast, lunch, or dinner). The participants indicated if their momentary eating patterns were consistent with their own baseline eating patterns in terms of healthiness or size of the meal. Further, participants described various characteristics of each eating situation. RESULTS:Eating consistency was positively predicted by trait self-control. Eating consistency was undermined by eating in the evening, eating with others, eating away from home, having consumed alcohol and having undertaken physical exercise. Interactions emerged between personality traits and situations, including punishment sensitivity, restraint, physical activity and alcohol consumption. CONCLUSION:Trait self-control and several eating situation variables were related to eating consistency. These findings provide a starting point for targeting interventions to improve consistency, suggesting that a focus on self-control skills, together with addressing contextual factors such as social situations and time of day, may be most promising. This work is a first step to provide people with the tools they need to maintain a consistently healthy lifestyle in a food-rich environment.