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Increased anthropogenic activities over the last decades have led to a gradual increase in chromium (Cr) content in the soil, which, due to its high mobility in soil, makes Cr accumulation in plants a serious threat to the health of animals and humans. The present study investigated the ameliorative effect of foliar-applied Si nanoparticles (SiF) and soil-applied SiNPs enriched biochar (SiBc) on the growth of wheat in Cr-polluted soil (CPS). Two levels of CPS were prepared, including 12.5 % and 25 % by adding Cr-polluted wastewater in the soil as soil 1 (S1) and soil 2 (S2), respectively for the pot experiment with a duration of 40 days. Cr stress significantly reduced wheat growth, however, combined application of SiF and SiBc improved root and shoot biomass production under Cr stress by (i) reducing Cr accumulation, (ii) increasing activities of antioxidant enzymes (ascorbate peroxidase and catalase), and (iii) increasing protein and total phenolic contents in both root and shoot respectively. Nonetheless, separate applications of SiF and SiBc effectively reduced Cr toxicity in shoot and root respectively, indicating a tissue-specific regulation of wheat growth under Cr. Later, the Langmuir and Freundlich adsorption isotherm analysis showed a maximum soil Cr adsorption capacity ∼ Q (max) of 40.6 mg g -1 and 59 mg g -1 at S1 and S2 respectively, while the life cycle impact assessment showed scores of -1 mg kg -1 and -211 mg kg -1 for Cr in agricultural soil and - 0.184 and - 38.7 for human health at S1 and S2 respectively in response to combined SiF + SiBC application, thus indicating the environment implication of Si nanoparticles and its biochar in ameliorating Cr toxicity in different environmental perspectives., Competing Interests: Declaration of competing interest The authors declared that there is no conflict of interest with any agency., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®., Methods: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system., Results: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1-55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022)., Conclusions: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy., (© 2024. The Author(s).)

As the key stage for purifying wastewater, elimination of emerging contaminants (ECs) is found to be fairly low in wastewater treatment plants (WWTPs). However, less knowledge is obtained regarding the transformation pathways between various chemical structures of ECs under different treatment processes. This study unveiled the transformation pathways of ECs with different structures in 15 WWTPs distributed across China by simplified network analysis (SNA) we proposed. After treatment, the molecular weight of the whole component of wastewater decreased and the hydrophilicity increased. There are significant differences in the structure of eliminated, consistent and formed pollutants. Amino acids, peptides, and analogues (AAPAs) were detected most frequently and most removable. Benzenoids were refractory. Triazoles were often produced. The high-frequency reactions in different WWTPs were similar, (de)methylation and dehydration occurred most frequently. Different biological treatment processes performed similarly, while some advanced treatment processes differed, such as a significant increase of -13.976 (2HO reaction) paired mass distances (PMDs) in the chlorine alone process. Further, the common structural transformation was uncovered. 4 anti-hypertensive drugs, including irbesartan, valsartan, olmesartan, and losartan, were identified, along with 22 transformation products (TPs) of them. OH 2 and H 2 O PMDs occurred most frequently and in 80.81 % of the parent-transformation product pairs, the intensity of the product was higher than parent in effluents, whose risk should be considered in future assessment activity. Together our results provide a macrography perspective on the transformation processes of ECs in WWTPs. In the future, selectively adopting wastewater treatment technology according to structures is conductive for eliminating recalcitrant ECs in WWTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Understanding the reaction mechanism of dissolved organic matter (DOM) during wastewater biotreatment is crucial for optimal DOM control. Here, we develop a directed paired mass distance (dPMD) method that constructs a molecular network displaying the reaction pathways of DOM. It couples direction inference and PMD analysis to extract the substrate-product relationships and delta masses of potentially paired reactants directly from sequential mass spectrometry data without formula assignment. Using this method, we analyze the influent and effluent samples from the bioprocesses of 12 wastewater treatment plants (WWTPs) and build a dPMD network to characterize the core reactome of DOM. The network shows that the first step of the transformation triggers reaction cascades that diversify the DOM, but the highly overlapped subsequent reaction pathways result in similar effluent DOM compositions across WWTPs despite varied influents. Mass changes exhibit consistent gain/loss preferences (e.g., +3.995 and -16.031) but different occurrences across WWTPs. Combined with genome-centric metatranscriptomics, we reveal the associations among dPMDs, enzymes, and microbes. Most enzymes are involved in oxygenation, (de)hydrogenation, demethylation, and hydration-related reactions but with different target substrates and expressed by various taxa, as exemplified by Proteobacteria , Actinobacteria , and Nitrospirae . Therefore, a functionally diverse community is pivotal for advanced DOM degradation.

Background: Previous studies have shown that high level of TILs in invasive lobular carcinoma (ILC) is associated with poor prognosis, contrary to that in TNBC and HER2-positive breast cancer., Methods: The densities of six immune cell markers and three immune checkpoints in the ILC microenvironment were detected by computational pathology analysis. Then, the LASSO cox regression model was used to construct an immune score (IS) and further evaluate its prognostic value., Results: In our ILC cohort, the low density of CD4, CD8, CD20, CD56, CD68, FOXP3, PD-1, and PD-L1 had significantly longer disease-free survival (DFS) and overall survival (OS); however, the low density of CTLA-4 was associated with shorter DFS and OS. Based on this, an IS was constructed, and patients with low-IS had significantly prolonged DFS (p < 0.0001) and OS (p < 0.0001). Multivariate analysis revealed that IS was an independent prognostic indicator for DFS and OS. Further analysis showed that IS may increase the prognostic value of TNM stage. We further explored the prognostic role of CD68 and FOXP3 in the transcriptional level and the corresponding ISm in the METABRIC dataset, and found that low proportion of CD68 and FOXP3 and their ISm were associated with longer OS, and ISm was also an independent prognostic factor for OS., Conclusion: IS was a promising biomarker to distinguish the prognosis in ILC patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The expansion of built-up land is currently being increasingly triggered by remote demand, thus disturbing the local process of carbon neutrality significantly. It is meaningful to understand the relations between regional development and carbon balance. To this end, we combine the multi-regional input-output model with the land system cellular automata model for potential effects (LANDSCAPE) to illustrate the impact that regional development has on the carbon burden. The results show that the expansion of built-up land results in a regional carbon burden through taking over ecological land and generating carbon emissions, to which the manufacturing industry land is the largest contributor. Regionally, developed regions exert the greatest influences on the changes in the regional carbon burden, mainly because the promotion of their development leads to the expansion of built-up land in all regions. Developing regions can impact undeveloped regions and themselves, while it is hard for undeveloped regions to change the regional carbon burden due to their low capacity to externally drive the expansion of built-up land. Meanwhile, the continuing development of developed regions exerts great pressure on carbon neutrality in both developing and undeveloped regions as they expand the "high-quality" built-up land themselves, which means that regional development may lead to changes in the carbon burden of regions which are less developed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Osteosarcoma (OS) is the most prevalent primary fatal bone neoplasm in adolescents and children owing to limited therapeutic methods. Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the roles of circRNAs in OS are still unclear., Methods: Firstly, we evaluate the differentially expressed circRNAs in 3 paired OS and corresponding adjacent nontumor tissue samples by circRNA microarray assay, finding a novel circRNA, circ&#95;001722, significantly upregulated in OS tissues and cells. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of OS cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was verified by dual-luciferase assay and RNA immunoprecipitation assay., Results: A novel circRNA, circ&#95;001722, is significantly upregulated in OS tissues and cells. Downregulation of circ&#95;0001722 can suppress proliferation and invasion of human OS cells in vitro and in vivo. Computational algorithms predict miR-204-5p can bind with circ&#95;0001722 and RUNX2 mRNA 3'UTR, which is verified by Dual-luciferase assay and RNA immunoprecipitation assay. Further functional experiments show that circ&#95;0001722 competitively binds to miR-204-5p and prevents it to decrease the level of RUNX2, which upregulates proliferation and invasion of human OS cells., Conclusion: Circ&#95;001722 is a novel tumor promotor in OS, and promotes the progression of OS via miR-204-5p/RUNX2 axis., (© 2023. The Author(s).)

Tertiary lymphoid structures (TLSs) play a crucial role in determining prognosis and response to immunotherapy in several solid malignancies. Nevertheless, the effect of TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) cohort in patients with breast cancer (BRCA) remains controversial. Based on TCGA-BRCA dataset (n = 866), 9-gene was identified to construct an TLS signature and further analyzed its prognostic value. Then, we explored the relationship of this TLS signature with molecular subtype, immune microenvironment, tumor mutational burden (TMB). High-TLS signature patients had a better overall survival (OS) than low-TLS signature patients, consistent with the results in the METABRIC cohort. Multivariate analysis revealed that TLS signature remained an independent prognostic indicator for OS. In addition, we established a nomogram with the integration of TLS signature and other independent variables to predict individual risk of death. The comprehensive results showed that patients with high TLS signature benefit from immunotherapy; the signature was also correlated with inhibition of cell proliferation pathways, low TP53 mutation rate, high infiltration of B cells, CD8 + T cells, CD4 + T cells, and M1 macrophages. Therefore, TLS signature is a promising biomarker to distinguish the prognosis and immune microenvironment in BRCA., (© 2023. Springer Nature Limited.)

The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention ( p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.

Curcumin (Cur) is a kind of polyphenol with a variety of topical pharmacological properties including antioxidant, analgesic and anti-inflammatory activities. However, its low water solubility and poor skin bioavailability limit its effectiveness. In the current study, we aimed to develop microemulsion-based keratin-chitosan gel for the improvement of the topical activity of Cur. The curcumin-loaded microemulsion (CME) was formulated and then loaded into the keratin-chitosan (KCS) gel to form the CME-KCS gel. The formulated CME-KCS gel was evaluated for its characterization, in vitro release, in vitro skin permeation and in vivo activity. The results showed that the developed CME-KCS gel had an orange-yellow and gel-like appearance. The particle size and zeta potential of the CME-KCS gel were 186.45 ± 0.75 nm and 9.42 ± 0.86 mV, respectively. The CME-KCS gel showed desirable viscoelasticity, spreadability, bioadhesion and controlled drug release, which was suitable for topical application. The in vitro skin permeation and retention study showed that the CME-KCS gel had better in vitro skin penetration than the Cur solution and achieved maximum skin drug retention (3.75 ± 0.24 μg/cm 2 ). In vivo experimental results confirmed that the CME-KCS gel was more effective than curcumin-loaded microemulsion (Cur-ME) in analgesic and anti-inflammatory activities. In addition, the CME-KCS gel did not cause any erythema or edema based on a mice skin irritation test. These findings indicated that the developed CME-KCS gel could improve the skin penetration and retention of Cur and could become a promising formulation for topical delivery to treat local diseases., Competing Interests: The authors declare no conflict of interest.

What Is Already Known on This Topic?: Chronic obstructive pulmonary disease (COPD) exacerbations increase household economic burden, but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden., What Is Added by This Report?: This study demonstrated the economic burden of COPD exacerbations, pneumonia, and hospitalization in COPD patients in China is substantial. Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately or together, were significantly associated with decreased economic burden., What Are the Implications for Public Health Practice?: Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23., Competing Interests: No conflicts of interest reported., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

To meet high-throughput screening of the residues of sulfonamides (SAs) with high sensitivity toward sulfamethazine (SM2) in milk samples, a new highly sensitive lateral flow immunoassay (LFA) based on amorphous carbon nanoparticles (ACNs) was developed. First, a group-specific monoclonal antibody 10H7 (mAb 10H7) that could recognize 25 SAs with high sensitivity toward SM2 (IC 50 value of 0.18 ng/mL) was prepared based on H1 as an immune hapten and H4 as a heterologous coating hapten. Then, mAb 10H7 was conjugated to ACNs as an immune probe for LFA development. Under the optimized conditions, the LFA could detect 25 SAs with the cut-off value toward SM2 of 2 ng/mL, which could meet the requirement for detection of SAs. In addition, the LFA developed was also used for screening SAs' residues in real milk samples, with results being consistent with HPLC-MS/MS. Thus, this LFA can be used as a high-throughput screening tool for detection of SAs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Medical image analysis is of tremendous importance in serving clinical diagnosis, treatment planning, as well as prognosis assessment. However, the image analysis process usually involves multiple modality-specific software and relies on rigorous manual operations, which is time-consuming and potentially low reproducible., Methods: We present an integrated platform - uAI Research Portal (uRP), to achieve one-stop analyses of multimodal images such as CT, MRI, and PET for clinical research applications. The proposed uRP adopts a modularized architecture to be multifunctional, extensible, and customizable., Results and Discussion: The uRP shows 3 advantages, as it 1) spans a wealth of algorithms for image processing including semi-automatic delineation, automatic segmentation, registration, classification, quantitative analysis, and image visualization, to realize a one-stop analytic pipeline, 2) integrates a variety of functional modules, which can be directly applied, combined, or customized for specific application domains, such as brain, pneumonia, and knee joint analyses, 3) enables full-stack analysis of one disease, including diagnosis, treatment planning, and prognosis assessment, as well as full-spectrum coverage for multiple disease applications. With the continuous development and inclusion of advanced algorithms, we expect this platform to largely simplify the clinical scientific research process and promote more and better discoveries., Competing Interests: JW, YX, XW, AL, YW, LC, JS, LW, YZ, XZ, ZX, FS, and DS are employees of Shanghai United Imaging Intelligence Co., Ltd, Shanghai, China. AI and MZ are employees of United Imaging Intelligence Co., Ltd., Cambridge, MA, United States. These companies have no role in designing and performing the surveillance and analyzing and interpreting the data., (© 2023 Wu, Xia, Wang, Wei, Liu, Innanje, Zheng, Chen, Shi, Wang, Zhan, Zhou, Xue, Shi and Shen.)

Diaveridine (DVD) has widespread use in food animals due to its antibacterial synergistic effects. This study revealed the metabolism, excretion, and tissue elimination of DVD in swine, chickens, and rats following oral gavage of 10 mg/kg b.w. tritium-labeled DVD using radioactive tracing coupled with liquid chromatography-electron spray ionization-ion trap-time-of-flight-mass spectrometry (LC-ESI-IT-TOF/MS). The metabolic pathways involved demethylation, α-hydroxylation, glucuronidation, and sulfonylation and produced four metabolites in swine (M0, DVD; M1, 3'/4'-demethyl-DVD; M2, 3'/4'-demethyl-DVD- O -glucuronide; M4, 2/4-glucuronidated-DVD) and five in chickens (M0∼M2; M3, α-hydroxy-DVD; M4) and rats (M0∼M3; M5, 3'/4'-demethyl-DVD- O -sulfation). M0 was dominant in the excreta of chicken and female and male rats, while M2 was mainly excreted in swine. Among the three species studied, M0 was the most persistent in the kidneys ( t 1/2 3.15-3.89 d); therefore, M0 kidney levels are residue monitoring targets. This study enabled a thorough comprehension of the metabolism and pharmacokinetic characteristics of DVD in animals.

Background: Nanocomposite Hydrogels (NHs) are 3D molecular networks formed by physically or covalently crosslinking polymer with nanoparticles or nanostructures, which are particularly suitable for serving as carriers for drug delivery systems. Many articles pertaining to the applications of Nanocomposite Hydrogels for drug delivery have been published, however, the use of bibliometric and visualized analysis in this area remains unstudied. The purpose of this bibliometric study intended to comprehensively analyze the knowledge domain, research hotspots and frontiers associated with the applications of Nanocomposite Hydrogels for drug delivery. Methods: We identified and retrieved the publications concerning the applications of NHs for drug delivery between 2003 and 2022 from Web of Science Core Collection Bibliometric and visualized analysis was utilized in this investigative study. Results: 631 articles meeting the inclusion criteria were identified and retrieved from WoSCC. Among those, 2,233 authors worldwide contributed in the studies, accompanied by an average annual article increase of 24.67%. The articles were co-authored by 764 institutions from 52 countries/regions, and China published the most, followed by Iran and the United States. Five institutions published more than 40 papers, namely Univ Tabriz ( n = 79), Tabriz Univ Med Sci ( n = 70), Islamic Azad Univ ( n = 49), Payame Noor Univ ( n = 42) and Texas A&M Univ ( n = 41). The articles were published in 198 journals, among which the International Journal of Biological Macromolecules ( n = 53) published the most articles, followed by Carbohydrate Polymers ( n = 24) and ACS Applied Materials and Interfaces ( n = 22). The top three journals most locally cited were Carbohydrate Polymers, Biomaterials and Advanced materials. The most productive author was Namazi H (29 articles), followed by Bardajee G (15 articles) and Zhang J (11 articles) and the researchers who worked closely with other ones usually published more papers. "Doxorubicin," "antibacterial" and "responsive hydrogels" represent the current research hotspots in this field and "cancer therapy" was a rising research topic in recent years. "(cancer) therapeutics" and "bioadhesive" represent the current research frontiers. Conclusion: This bibliometric and visualized analysis offered an investigative study and comprehensive understanding of publications regarding the applications of Nanocomposite Hydrogels for drug delivery from 2003 to 2022. The outcome of this study would provide insights for researchers in the field of Nanocomposite Hydrogels applications for drug delivery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XQ declared a shared parent affiliation with the authors HT and PH to the handling editor at the time of review., (Copyright © 2023 Wang, Fu, Fu, Jiang, Wang, Tong, Xie, Huang and Sun.)

Background: In an increasingly diverse United States (US) population, racial disparities in preterm birth outcomes continue to widen., Objective: In this study, we examined temporal trends and risk of preterm birth among Asian American women over a quarter century (1992-2018)., Study Design: This is a retrospective cohort study using the 1992-2018 Natality data files. We conducted joinpoint regression analyses to examine trends in preterm birth among Asian Americans and non-Hispanic (NH) Whites. Bivariate and multivariable analyses were used to identify risk factors associated with preterm birth among Asian Americans and their ethnic sub-groups as compared to NH-Whites., Results: There were a total of 251,278 preterm births among Asian American women, corresponding to a rate of 10.0%, which was relatively stable over time. The incidence of extremely, very and moderate-to-late preterm birth among Asian Americans was 0.4%, 0.9% and 8.7% respectively. Overall, Asian American women exhibited lower adjusted odds (OR = 0.92; 95% CI: 0.88-0.97) of preterm birth than their NH-White counterparts. Comparing Asian American subgroups to NH-Whites, Filipinas and Vietnamese mothers had increased adjusted odds, whereas Chinese, Korean, Japanese and Asian Indian women showed decreased adjusted odds for preterm birth., Conclusion: The risk of preterm birth varied among the ethnic subgroups of Asian Americans in the United States. Future studies should explore the socio-cultural and environmental nuances that might explain these differences.

Challenges associated with topical analgesics and anti-inflammatory drugs include poor drug penetration and retention at the desired lesion site. Therefore, improving these challenges would help to reduce the toxic and side effects caused by drug absorption into the systemic circulation and improve the therapeutic efficacy of topical therapeutic drugs. Pentapeptide (KTTKS) is a signal peptide in skin tissue, it can be recognized and bound by signal recognition particles. In the current study, we successfully prepared novel indomethacin (IMC) loaded KTTKS-modified ethosomes (IMC-KTTKS-Es), and the physicochemical properties and topical efficacy were investigated. Results showed that the prepared IMC-KTTKS-Es displayed a particle size of about 244 nm, a negative charge, good deformability, and encapsulation efficiency (EE) exceeding 80% for IMC, with a sustained release pattern. In vitro percutaneous permeation studies revealed that the skin retention was increased after the drug was loaded in the IMC-KTTKS-Es. Confocal laser scanning microscopy also showed improved skin retention of IMC-KTTKS-Es. In addition, IMC-KTTKS-Es showed improved topical analgesic and anti-inflammatory activity with no potentially hazardous skin irritation. This study suggested that the IMC-KTTKS-Es might be an effective drug carrier for topical skin therapy with a good safety profile.

Background and Objective: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes., Methods: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression., Results: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group., Conclusion: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest., (© 2022 Asian Pacific Society of Respirology.)

Objective: Two-photon polymerization (TPP) utilizes an optical nonlinear absorption process to initiate the polymerization of photopolymerizable materials. To date, it is the only technique capable of fabricating complex 3D microstructures with finely adjusted geometry on the cell and sub-cell scales. TPP shows a very promising potential in biomedical applications related to high-resolution features, including drug delivery, tissue engineering, microfluidic devices, and so forth. Therefore, it is of high significance to grasp the global scientific achievements in this field. An analysis of publications concerning the applications of TPP in the biomedical field was performed, and the knowledge domain, research hotspots, frontiers, and research directions in this topic were identified according to the research results. Methods: The publications concerning TPP applications in biomedical field were retrieved from WoSCC between 2003 and 2022, Bibliometrics and visual analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study. Results: A total of 415 publications regarding the TPP applications in the biomedical field were retrieved from WoSCC, including 377 articles, and 38 review articles. The studies pertaining to the biomedical applications of TPP began back in 2003 and showed an upward trend constantly. Especially in the recent 5 years, studies of TPP in biomedical field have increased rapidly, with the number of publications from 2017 to 2021 accounting for 52.29% of the total. In terms of output, China was the leading country and Chinese Acad Sci, Tech Inst Phys and Chem was the leading institution. The United States showed the closest cooperation with other countries. ACS applied materials and interfaces was the most prolific journal ( n = 13), followed by Biofabrication ( n = 11) and Optics express ( n = 10). The journals having the top cited papers were Biomaterials, Advanced materials, and Applied physic letters. The most productive author was Aleksandr Ovsianikov (27 articles). Meanwhile, researchers who had close cooperation with other researchers were also prolific authors. "cell behavior", " (tissue engineering) scaffolds", "biomaterials," and "hydrogel" were the main co-occurrence keywords and "additional manufacturing", "3D printing," and "microstructures" were the recent burst keywords. The Keyword clusters, "stem cells," and "mucosal delivery", appeared recently. A paper reporting unprecedented high-resolution bull models fabricated by TPP was the most locally cited reference (cited 60 times). "Magnetic actuation" and "additive manufacturing" were recently co-cited reference clusters and an article concerning ultracompact compound lens systems manufactured by TPP was the latest burst reference. Conclusion: The applications of TPP in biomedical field is an interdisciplinary research topic and the development of this field requires the active collaboration of researchers and experts from all relevant disciplines. Bringing up a better utilization of TPP as an additive manufacturing technology to better serve the biomedical development has always been the research focus in this field. Research on stem cells behaviors and mucosal delivery based on microstructures fabricated using TPP were becoming new hotspots. And it can be predicted that using TPP as a sourcing technique to fabricate biomedical-related structures and devices is a new research direction. In addition, the research of functional polymers, such as magnetic-driven polymers, was the frontier topic of TPP biomedical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fu, Jing, Lin, Wang, Jiang, Yu and Sun.)

The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of -13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 μg/cm 2 ). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Niu, Yuan, Liu, Wang, Tang, Wang, Qi, Zhang, Ya and Fan.)

Background: The poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs., Methods: In this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed., Results: The mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and -26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin., Conclusion: CUR-M might be a promising and safe drug delivery system for the treatment of topical diseases., Competing Interests: The authors report no conflicts of interest for this work., (© 2022 Niu et al.)

The needs for high-resolution, well-defined and complex 3D microstructures in diverse fields call for the rapid development of novel 3D microfabrication techniques. Among those, two-photon polymerization (TPP) attracted extensive attention owing to its unique and useful characteristics. As an approach to implementing additive manufacturing, TPP has truly 3D writing ability to fabricate artificially designed constructs with arbitrary geometry. The spatial resolution of the manufactured structures via TPP can exceed the diffraction limit. The 3D structures fabricated by TPP could properly mimic the microenvironment of natural extracellular matrix, providing powerful tools for the study of cell behavior. TPP can meet the requirements of manufacturing technique for 3D scaffolds (engineering cell culture matrices) used in cytobiology, tissue engineering and regenerative medicine. In this review, we demonstrated the development in 3D microfabrication techniques and we presented an overview of the applications of TPP as an advanced manufacturing technique in complex 3D biomedical scaffolds fabrication. Given this multidisciplinary field, we discussed the perspectives of physics, materials science, chemistry, biomedicine and mechanical engineering. Additionally, we dived into the principles of tow-photon absorption (TPA) and TPP, requirements of 3D biomedical scaffolders, developed-to-date materials and chemical approaches used by TPP and manufacturing strategies based on mechanical engineering. In the end, we draw out the limitations of TPP on 3D manufacturing for now along with some prospects of its future outlook towards the fabrication of 3D biomedical scaffolds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jing, Fu, Yu, Sun and Wang.)

With the growing demand for developing lasers with high stability and integration, temperature-insensitive gain materials are highly desirable. Here, temperature-insensitive near-infrared (NIR) optical gain from low-toxicity Ag 2 Se quantum dots (QDs) is reported. Due to the large energy splitting between the band-edge hole state and the following state (∼430 meV), the thermal depopulation of the band-edge hole state in Ag 2 Se QDs is significantly suppressed. The long biexciton lifetime (245 ps at 300 K) of the QDs is sufficient to support the establishment of amplified spontaneous emission (ASE). Consequently, the characteristic temperature of the ASE threshold for the Ag 2 Se QD film is as high as 360 K, and efficient NIR ASE is observed up to 340 K. In addition, when the temperature is lower than 200 K, the ASE peak position is temperature insensitive because acoustic phonons cannot be effectively excited. Our findings reveal that Ag 2 Se QDs can be utilized as an excellent gain material for environmentally friendly temperature-insensitive NIR lasers.

The characteristics of dissolved organic matter (DOM) can significantly affect the degradation of target compounds by the advanced oxidation processes. In this study, the effects of the different hydrophobicity/hydrophilicity fractions, molecular weight (MW) fractions, fluorescence components and molecular components of DOM extracted from municipal wastewater on the degradation of 4 pharmaceutically active compounds (PhACs), including carbamazepine, clofibric acid, atenolol and erythromycin by the UV/H 2 O 2 process were investigated. The results showed that the degradation rate constants of 4 PhACs decreased dramatically in the presence of DOM. The linear regressions of 4 PhACs degradation as a function of specific fluorescence intensity (SFI) are exhibited during the degradation of 4 PhACs and the SFI may be used to evaluate effect of DOM on target compounds in wastewater. The hydrophobic acid (HPO-A) exhibited the strongest inhibitory effect on degradation of 4 PhACs during oxidation process. The small MW fractions of DOM significantly inhibited the degradation of 4 PhACs during oxidation process. Among three fluorescence components, hydrophobic humic-like substances may significantly inhibit the degradation of 4 PhACs during oxidation process. At the molecular level, the formulas may be derived from terrestrial sources. CHO compound may significantly inhibit the degradation of 4 PhACs during oxidation process on formula classes. The unsaturated hydrocarbons, carbohydrates and tannins compounds may significantly inhibit the effectiveness of the UV/H 2 O 2 process on compound classes., (Copyright © 2021. Published by Elsevier B.V.)

To reduce matrix interference and realize simultaneous detection of multiple homologous compounds (trimethoprim (TMP), diaveridine (DVD), ormetoprim (OMP), baquiloprim (BQP), and aditoprim (ADP) in pig, cattle, chicken, and fish muscles), an immunomagnetic bead (IMB)-based sample purification pretreatment with HPLC-UV was developed. A broad-spectrum monoclonal antibody (mAb, named 14C6) was prepared and conjugated with carboxylic-acid-functionalized magnetic nanoparticles using the active ester method to obtain IMBs for sample purification. The extraction solvent was optimized based on the extraction efficiency. Good linearity was observed for all the five analytes (10-200 μg/kg) with the LOD and LOQ of 5 and 10 μg/kg, respectively. The mean recoveries ranged from 62.5% to 76.9%, while the coefficient of variation was <12.2%. The IMB method afforded greater sample purification and enrichment than those achieved with the SPE column-based conventional method. Hence, the IMB-based sample purification is a useful tool to determine 2,4-diaminopyrimidine residues in edible animal tissues., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The importance and sensitivity of the time dimension in the emergency medical service (EMS) field have been widely recognized in recent years. However, the EMS spatio-temporal disparity remains partially uncovered in traditional accessibility measurements due to EMS's context-sensitive characteristics and demand specificity. In this study, we obtained dynamic traffic conditions and realistic EMS demand from online map services and historical emergency calls-out data, and then developed three location-based spatio-temporal EMS accessibility measurements. The empirical results demonstrate that the three different spatio-temporal EMS accessibility have a complex relationship, and are beneficial for measuring the EMS spatio-temporal disparity in different scenarios with distinct competitive effects. Ultimately, we emphasized four original EMS accessibility patterns, which helped us uncover significantly well-served or underserved areas. This study contributes to optimize the layout of EMS resources by understanding the regularity of EMS spatio-temporal disparity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation. After a single oral administration of 3 H-DVD (10 mg/kg BW), three radioactive compounds (D0: DVD; D1: 3'-desmethyl-DVD; and D2: monoglucuronide of 3'-desmethyl-DVD) were identified in pig plasma, while only two radioactive compounds (D0 and D2) were identified in chicken plasma. In both species, the C max values for all detected compounds were reached at 2 h after dosing. The C max order was D2 (1.38 μg/ml) > D0 (0.49 μg/ml) > D1 (0.24 μg/ml) in pigs and D0 (1.55 μg/ml) > D2 (0.27 μg/ml) in chickens. The longer t 1/2 (elimination half-life) of D0 contributed to the slow elimination of DVD-related compounds. The t 1/2β of D0 in pigs (66.41 h) was significantly longer than that in chickens (48.30 h), but the t 1/2 of total DVD-related metabolites in pigs (42.86 h) was lower than that in chickens (56.11 h). These findings suggested that the metabolism and pharmacokinetics of DVD in pigs and chickens were significantly different, and that this would affect its effectiveness, toxicology, and food safety in these animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wen, Pan, Wang, Zhou, Mi, Liu, Qu and Huang.)

Lysozymes are naturally occurring enzymes present in a variety of biological organisms, such as bacteria, fungi, and animal bodily secretions and tissues. It is also the main ingredient of many ethnomedicines. It is well known that lysozymes and lysozyme-like enzymes can be used as anti-bacterial agents by degrading bacterial cell wall peptidoglycan that leads to cell death, and can also inhibit fungi, yeasts, and viruses. In addition to its direct antimicrobial activity, lysozyme is also an important component of the innate immune system in most mammals. Increasing evidence has shown the immune-modulatory effects of lysozymes against infection and inflammation. More recently, studies have revealed the anti-cancer activities of lysozyme in multiple types of tumors, potentially through its immune-modulatory activities. In this review, we summarized the major functions and underlying mechanisms of lysozymes derived from animal and plant sources. We highlighted the therapeutic applications and recent advances of lysozymes in cancers, hypertension, and viral diseases, aiming toseeking alternative therapies for standard medical treatment bypassing side effects. We also evaluated the role of lysozyme as a promising cancer marker for prognosis to indicate the outcomes recurrence for patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Li, Wang, Guo, Liu, Meng, Zhang, Li, Cong and Sun.)

Background: Triple-negative breast cancer (TNBC) represents about 19% of all breast cancer cases in the Chinese population. Lack of targeted therapy contributes to the poorer outcomes compared with other breast cancer subtypes. Comprehensive genomic profiling helps to explore the clinically relevant genomic alterations (CRGAs) and potential therapeutic targets in very-early-relapsed TNBC patients., Methods: Formalin-fixed paraffin-embedded (FFPE) tumour tissue specimens from 23 patients with very-early-relapsed TNBC and 13 patients with disease-free survival (DFS) more than 36 months were tested by FoundationOne CDx (F1CDx) in 324 genes and select gene rearrangements, along with genomic signatures including microsatellite instability (MSI) and tumour mutational burden (TMB)., Results: In total, 137 CRGAs were detected in the 23 very-early-relapsed TNBC patients, averaging six alterations per sample. The mean TMB was 4 Muts/Mb, which was higher than that in non-recurrence patients, and is statistically significant. The top-ranked altered genes were TP53 (83%), PTEN (35%), RB1 (30%), PIK3CA (26%) and BRCA1 (22%). RB1 mutation carriers had shorter DFS. Notably, 100% of these patients had at least one CRGA, and 87% of patients had at least one actionable alteration. In pathway analysis, patients who carried a mutation in the cell cycle pathway were more likely to experience very early recurrence. Strikingly, we detected one patient with ERBB2 amplification and one patient with ERBB2 exon20 insertion, both of which were missed by immunohistochemistry (IHC). We also detected novel alterations of ROS1-EPHA7 fusion for the first time, which has not been reported in breast cancer before., Conclusions: The comprehensive genomic profiling can identify novel treatment targets and address the limited options in TNBC patients. Therefore, incorporating F1CDx into TNBC may shed light on novel therapeutic opportunities for these very-early-relapsed TNBC patients.

Multifunctional cultivated land has both sides of supply and demand, and their matches are very important to boost the high-quality development of agriculture and rural areas. The supply-demand match index and GIS spatial analysis were employed to explore the supply-demand mismatches and synergic strategies of multifunctional cultivated land. Taking the Wuhan Metropolitan Area (WMA), China as an example, we obtained the following results: (1) There were obvious supply-demand mismatches of multifunctional cultivated land in the production function, ecological function, and landscape culture function. The spatial distribution of supply-demand mismatches of the three different functions of cultivated land is different. The supply of cultivated land production function is less than the demand, while the supply of landscape culture function is greater than the demand. The supply matches the demand of cultivated land in the ecological function. (2) The supply-demand mismatches of multifunctional cultivated land have scale effects. From the 1 km × 1 km grid scale to the township, county (district), and prefecture-level city scales, the proportion of deficit regions of production function and ecological function decreases with increasing scale. In contrast, the deficit regions of landscape culture function are always concentrated in the center of the WMA. It is considered that we should improve the supply of cultivated land in the production function, protect ecological function and enhance the demand of landscape culture function. Moreover, the management of multifunctional cultivated land needs to strengthen the multiscale spatial linkage and differential strategies of the supply side and demand side., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We developed a sensitive and reliable method by coupling radiotracing with LC/MS-IT-TOF to identify diaveridine metabolites. Tritium-labeled diaveridine was orally administered to pigs and their organs, blood, bile, and excreta were collected. Under optimized conditions, radioactive recovery was >90% and the highest numbers of metabolites were detected. MCX-based solid-phase extraction was conducted for urine, plasma, and bile purification. Methanol-chloroform 1:1 (v/v), methanol-chloroform 6:1 (v/v), methanol, methanol-chloroform 1:1 (v/v), and methanol were used as solvents to extract feces, liver, kidney, fat and muscle, respectively. The method validation confirmed satisfactory 3 H-H exchange efficiency (<5%), chromatographic column efficiency (≥97.5%), LOQ (10.73 μg/kg), and analytical accuracy (97.6-107.8%) and precision (RSD < 5%). Moreover, novel in vivo metabolites were detected in the pigs, including D2 (3'-desmethyl-diaveridine monoglucuronide), D3 (diaveridine monoglucuronide). Hence, the analytical method developed herein lays an empirical foundation for further systematic studies of the diaveridine metabolism., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancers are highly heterogeneous and typically contain a small subset of drug-resisting cells called tumor initiating cells or cancer stem cells (CSCs). CSCs can self-renew, divide asymmetrically, and often cause tumor invasion and metastasis. Therefore, treatments specifically targeting CSCs are critical to improve patient survival. Recently, we identified a highly specific peptidomimetic (peptoid - PCS2) that selectively binds to the CSC subpopulation of lung cancer over the remaining cancer cells (non-CSCs). Subsequently, we identified plectin as the target of PCS2. Plectin is an intracellular structural protein, which is involved in tumor invasion and metastasis when it appears on cell surface. While PCS2 monomer did not display any anti-cancer activity, we designed a series of homo-dimeric versions of PCS2, and identified PCS2D1.2 optimized homo-dimer that displayed highly specific cytotoxicity towards CSCs over non-CSCs. PCS2D1.2 effectively blocked the in vitro colony formation and cell migration, hallmarks of CSCs. Furthermore, PCS2D1.2 reduced the in vivo tumor formation. In both in vitro and in vivo studies, PCS2D1.2 effectively reduced plectin expression and/or plectin-rich CSCs, but had no effect on non-CSCs. Therefore, PCS2D1.2 has the potential to be developed as a highly CSC specific drug candidate, which can be used in combination with current anti-cancer drugs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: HR+/HER2- breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2- non-pCR populations, it is essential to accurate identification new prognostic markers., Materials and Methods: The study retrospectively analyzed 105 stage II-III patients who were diagnosed with HR+/HER2- BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller-Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures., Results: Among the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) ( p = 0.004, p = 0.021, and p = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1-2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4-5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10-0.80; p = 0.018]. DFS was longer in the good response (MP grades 3-4) group than in the poor response (MP grades 1-2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05-0.47; p = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS ( p = 0.048). Due to the short median follow-up time of 34.5 months (5.9-75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival., Conclusion: The study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Luo, Lu, Jiang, Hong, Lee, Zhang, Zhou, Wang and Xu.)

Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients. Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events. Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post-vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion ( P = .10) and seroprotection ( P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0-25.1), 12.2 (95% CI: 9.6-15.4), and 31.8 (95% CI: 26.1-38.8) at baseline, and 267.0 (95% CI: 213.8-333.4), 190.3 (95% CI: 151.7-238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination. Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.

Understanding the degradation of dissolved organic matter (DOM) is vital for optimizing DOM control. However, the microbe-mediated DOM transformation during wastewater treatment remains poorly characterized. Here, microbes and DOM along full-scale biotreatment processes were simultaneously characterized using comparative genomics and high-resolution mass spectrometry-based reactomics. Biotreatments significantly increased DOM's aromaticity and unsaturation due to the overproduced lignin and polyphenol analogs. DOM was diversified by over five times in richness, with thousands of nitrogenous and sulfur-containing compounds generated through microbe-mediated oxidoreduction, functional group transfer, and C-N and C-S bond formation. Network analysis demonstrated microbial division of labor in DOM transformation. However, their roles were determined by their functional traits rather than taxa. Specifically, network and module hubs exhibited rapid growth potentials and broad substrate affinities but were deficient in xenobiotics-metabolism-associated genes. They were mainly correlated to liable DOM consumption and its transformation to recalcitrant compounds. In contrast, connectors and peripherals were potential degraders of recalcitrant DOM but slow in growth. They showed specialized associations with fewer DOM molecules and probably fed on metabolites of hub microbes. Thus, developing technologies (e.g., carriers) to selectively enrich peripheral degraders and consequently decouple the liable and recalcitrant DOM transformation processes may advance DOM removal.

Objective: To examine temporal trends of eclampsia by plurality in the US spanning three decades (1989-2018); and to investigate risk factors for eclampsia among singleton and multiple pregnancies in the US during the study period., Study Design: We conducted a retrospective cohort study using the Natality data files, including information on all births within the gestational age of 20-42 weeks from 1989 through 2018. We used joinpoint regression analysis to evaluate trends in rates of eclampsia over the study period. We employed logistic regression models to examine the association between plurality and eclampsia after adjusting for socio-demographic and gestational factors., Main Outcome Measures: The primary outcome was eclampsia among singleton and multiple pregnancies., Findings: There was a 2.8% (95% CI: -5.4, -0.1) average annual reduction in eclampsia rates among singletons, whereas among multiples there was a decline of about 3.7% (95% CI: -6.4, -1.0) annually. Mothers with multiple pregnancies had three-fold increased adjusted odds (OR = 95% CI: 2.95-3.21) of experiencing eclampsia when compared to those with singleton gestations. Non-Hispanic (NH) Black mothers with singletons had 37% greater adjusted odds of developing eclampsia than their NH-White peers (95%CI: 1.33-1.42)., Conclusion: There was an overall decreasing trend in eclampsia incidence in the US from 1989 to 2018, regardless of plurality. The occurrence of eclampsia was associated with plurality, race/ethnicity, maternal age and maternal BMI. Given the heterogeneity in clinical presentations of eclampsia, personalized/standardized risk prediction models are needed to enable consistent diagnosis and timely intervention., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Wastewater treatment plants (WWTPs) are the main sources of emerging contaminants (ECs) in aquatic environment. However, the standards for limiting emerging pollutants in effluent are extremely lacking. We investigated the occurrence and removal of emerging pollutants in 16 WWTPs in China using non-target analysis. 568 substances screened out were divided into 9 kinds including 167 pharmaceuticals, 113 natural substances, 85 pesticides, 86 endogenous substances, 64 chemical raw materials, 14 personal care products, 17 food additives, 6 hormones and 16 others. And they were divided into 5 fates. Pesticides and pharmaceutical compounds seemed to be the most notable categories, the kinds detected in each sample is the largest compared with other compounds. Besides, the average removal rate of pesticides and pharmaceuticals in all WWTPs were the lowest, at 9.54% and 23.77%, respectively. Priority pollutants were screened by considering distribution of pollutants with different fates. Pollutants with the same fate especially "consistent" in different WWTPs had attracted attention. 4 potential priority pollutants including metoprolol, carbamazepine, 10, 11-dihydro-10, 11-dihydroxycarbamazepine and irbesartan were proposed. And it was found that the 4 compounds, "consistent suspects" and "consistent non-targets" had similar rankings of removal rate in 16 WWTPs, which can reflect the performance of different WWTPs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The compositional characteristics of dissolved organic matter (DOM) in pharmaceutical wastewater effluent can affect the further improvement and application of the ozone treatment process. The present study investigated the changes of chemical structures, molecular weight (MW) distribution, hydrophobicity/hydrophilicity distribution, fluorescence properties and the molecular composition of DOM in pharmaceutical wastewater effluent during ozonation. Besides, the toxicity change of pharmaceutical wastewater effluent during ozonation was estimated. The results show that ozone is prone to attack high MW fractions, which contributes the most to the UV 254 value and could improve the biodegradability of refractory DOM in pharmaceutical wastewater effluent. Hydrophobic acid contained the most aromatic and unsaturated bonded organic matter, and was more readily oxidized under ozonation. In fluorescent components, ozonation significantly decreased humic-like acid compounds, and hydrophobic humic-like compounds exhibited the highest removal through parallel factor analysis. At the molecular level, the main organics removed by ozone were compounds with high H/C and low O/C, especially compounds where H/C >1.5. The CHO, CHON and CHOS compounds exhibited high removal under ozonation in formula classes. Lignin compounds, condensed aromatics compounds, and unsaturated hydrocarbons were effectively removed by ozone in compound classes. After ozonation, the number of lipid and sugar compounds increased. In addition, O/Cwa (the intensity-weighted average parameters of O/C) and NOSCwa (nominal oxidation state of carbon) were significantly positively correlated with acute toxicity on the luminescence. With the increase of ozone dose, the acute toxicity of pharmaceutical wastewater effluent after ozonation first decreased and then increased., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microbe-derived dissolved organic nitrogen (mDON) can readily induce harmful phytoplankton blooms, and thus, restricting its discharges is necessary. Recently, algae biofilm (AB) has attracted increasing interest for its advantages in nutrient recovery. However, its features in mDON control remain unexplored. Herein, AB's mDON formation and utilization performance, molecular characteristics, and metabolic traits have been investigated, with activated sludge (AS) as the benchmark for comparisons. Comparatively, AB reduced mDON formation by 83% when fed with DON-free wastewater. When fed with AS's effluent, it consumed at least 72% of the exogenous mDON and notably reduced the amount of protein/amino sugar-like compounds. Irrespective of the influent, AB ultimately produced more various unsaturated hydrocarbon and lignin analogues. Redundancy and network analysis highlighted the algal-bacterial synergistic effects exemplified by cross-feeding in reducing mDON concentrations and shaping mDON pools. Moreover, metagenomics-based metabolic reconstruction revealed that cyanobacteria Limnothrix and Kamptonema spp. facilitated mDON uptake, ammonification, and recycling, which supplied the extensive nitrogen assimilatory demand for amino acids, vitamins, and cofactors biosynthesis, and therefore promoted mDON scavenging. Our findings demonstrate that regardless of the secondary or tertiary process, cyanobacteria-dominated AB is promising to minimize bioavailable mDON discharges, which has implications for future eutrophication control.

Cropland protection strategies have provided a strong contribution to limit cropland transformation worldwide. However, it negatively affects ecological land (e.g., forest, grassland, and wetland). Identifying a win-win approach for cropland protection and ecological conservation is important. Land use optimization plays a vital role in solving conflicts among land uses. Thus, in this research, taking China (mainland) as the study area, we optimized the spatial distribution of urban land and cropland to balance the requirement of cropland protection strategies and their negative effects on ecological land according to the spatial heterogeneity of land agricultural production capacity by using the LAND System Cellular Automata model for Potential Effects (LANDSCAPE). Specifically, we developed three optimization scenarios from compensational, occupancy, and occupancy and compensational sectors. We also developed one non-optimization scenario to remain comparable. Results show that compared with the non-optimization scenario, the reduced loss of ecological land in compensational, occupancy, and occupancy and compensational optimization scenario is 7180, 247, and 7277 km 2 , respectively. Our research indicates that we should prioritize the quality of compensated cropland when developing cropland protection strategies and planning, considering the low efficiency of the occupancy optimization and the cost of policymaking and implementing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

What Is Already Known on This Topic?: The global burden of chronic obstructive pulmonary disease (COPD) is serious. Pneumococcal infection is associated with acute exacerbations of COPD (AECOPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for COPD patients to decrease AECOPD due to pneumococcus, but evidence on the immunogenicity of PPSV23 in COPD patients is limited., What Is Added by This Report?: This study showed good immunogenicity of one dose of PPSV23 in COPD patients. Antibody levels against all 23 vaccine serotypes were assessed before and four weeks after vaccination of COPD patients with one dose of PPSV23. The percent of COPD patients who had two-fold increases in pneumococcal antibody levels following vaccination ranged from 65.2% (serotype 3) to 94.4% (serotype 2). There were statistically significant differences in immunogenicity by serotype., What Are the Implications for Public Health Practice?: This study supports current recommendations for PPSV23 vaccination of COPD patients in China to provide protection from pneumococcal diseases., Competing Interests: Conflicts of interest: We declare no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2021.)

Background: Denitrifying phosphorus removal sludge (DPRS) is widely adopted for nitrogen and phosphorus removal in wastewater treatment but faces threats from heavy metals. However, a lack of understanding of the taxon-specific heavy metal-resistance mechanisms hinders the targeted optimization of DPRS's robustness in nutrient removal., Results: We obtained 403 high- or medium-quality metagenome-assembled genomes from DPRS treated by elevating cadmium, nickel, and chromium pressure. Then, the proteomic responses of individual taxa under heavy metal pressures were characterized, with an emphasis on functions involving heavy metal resistance and maintenance of nutrient metabolism. When oxygen availability was constrained by high-concentration heavy metals, comammox Nitrospira overproduced highly oxygen-affinitive hemoglobin and electron-transporting cytochrome c-like proteins, underpinning its ability to enhance oxygen acquisition and utilization. In contrast, Nitrosomonas overexpressed ammonia monooxygenase and nitrite reductase to facilitate the partial nitrification and denitrification process for maintaining nitrogen removal. Comparisons between phosphorus-accumulating organisms (PAOs) demonstrated different heavy metal-resistance mechanisms adopted by Dechloromonas and Candidatus Accumulibacter, despite their high genomic similarities. In particular, Dechloromonas outcompeted the canonical PAO Candidatus Accumulibacter in synthesizing polyphosphate, a potential public good for heavy metal detoxification. The superiority of Dechloromonas in energy utilization, radical elimination, and damaged cell component repair also contributed to its dominance under heavy metal pressures. Moreover, the enrichment analysis revealed that functions involved in extracellular polymeric substance formation, siderophore activity, and heavy metal efflux were significantly overexpressed due to the related activities of specific taxa., Conclusions: Our study demonstrates that heavy metal-resistance mechanisms within a multipartite community are highly heterogeneous between different taxa. These findings provide a fundamental understanding of how the heterogeneity of individual microorganisms contributes to the metabolic versatility and robustness of microbiomes inhabiting dynamic environments, which is vital for manipulating the adaptation of microbial assemblages under adverse environmental stimuli. Video abstract.

COX-2 fluorescent probes are promising tools for cancer diagnosis. Such probes have been conventionally designed by conjugating a fluorophore to COX-2 inhibitors through lengthy synthetic processes. Herein, a type of fluorescent probe for COX-2 imaging has been developed using a single-step process from rofecoxib. In total, six rofecoxib analogues were designed using this unique strategy. Several analogues retained comparative COX-2 targeting activity of rofecoxib and also exhibited attractive fluorescent properties, which were investigated using a combination of experimental and theoretical approaches. The most potent analogue, 2a1 , displayed strong fluorescent imaging of COX-2 in HeLa cells overexpressing COX-2 compared to Raw 264.7 cells and celecoxib-treated HeLa cells that expressed low levels of COX-2. Notably, our studies indicate that 2a1 can differentiate human cancer tissue from adjacent tissue with much brighter fluorescence either in histological section or cultured 3D organoids. These results illustrate the potential of 2a1 as a COX-2 near infrared fluorescent probe for human cancer imaging in clinical settings.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer., Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective., Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients., Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Objective: To examine trends in rates of preterm birth by race and plurality; to evaluate the association between race, plurality, and phenotypes of preterm birth., Study Design: Temporal trends analyses for preterm birth by race and plurality were performed for the years 1971-2018. Adjusted logistic regression models were utilized to evaluate the association between race, plurality, and phenotypes of preterm birth., Results: We observed that 1105,266 (0.7%), 1901,604 (1.2%), and 14,769,746 (9.3%) births belonged to extreme preterm, very preterm, and moderate-to-late preterm categories, respectively. We also observed that the risk of extreme preterm (RR: 2.69, 95% CI: 2.642-2.75) was highest for Black mothers as compared to White mothers., Conclusion: Over the study period, preterm births disproportionately impacted Black mothers as well as pregnancies of higher plurality. With the persistence of racial disparities and growing trend of delayed childbearing and multiple pregnancies, targeted intervention is necessitated toward these vulnerable subgroups.

A homogeneous fluorescence quenching immunoassay is described for simultaneous separation and detection of aflatoxin M 1 (AFM 1 ) in milk. The novel assay relies on monoclonal antibody (mAb) functionalized Fe 3 O 4 decorated reduced-graphene oxide (rGO-Fe 3 O 4 -mAb) as both capture probe and energy acceptor, combined with tetramethylrhodamine cadaverine-labeled aflatoxin B 1 (AFB 1 -TRCA) as the energy donor. In the assay, AFB 1 -TRCA binds to rGO-Fe 3 O 4 -mAb in the absence of AFM 1 , quenching the fluorescence of TRCA by resonance energy transfer. Significantly, the immunoassay integrates sample preparation and detection into a single step, by using magnetic graphene composites to avoid washing and centrifugation steps, and the assay can be completed within 10 min. Under optimized conditions, the visual and quantitative detection limits of the assay for AFM 1 were 50 and 3.8 ng L -1 , respectively, which were significantly lower than those obtained by fluorescence polarization immunoassay using the same immunoreagents. Owing to its operation and highly sensitivity, the proposed assay provides a powerful tool for the detection of AFM 1 .

With the rapidly worldwide spread of Coronavirus disease (COVID-19), it is of great importance to conduct early diagnosis of COVID-19 and predict the conversion time that patients possibly convert to the severe stage, for designing effective treatment plans and reducing the clinicians' workloads. In this study, we propose a joint classification and regression method to determine whether the patient would develop severe symptoms in the later time formulated as a classification task, and if yes, the conversion time will be predicted formulated as a classification task. To do this, the proposed method takes into account 1) the weight for each sample to reduce the outliers' influence and explore the problem of imbalance classification, and 2) the weight for each feature via a sparsity regularization term to remove the redundant features of the high-dimensional data and learn the shared information across two tasks, i.e., the classification and the regression. To our knowledge, this study is the first work to jointly predict the disease progression and the conversion time, which could help clinicians to deal with the potential severe cases in time or even save the patients' lives. Experimental analysis was conducted on a real data set from two hospitals with 408 chest computed tomography (CT) scans. Results show that our method achieves the best classification (e.g., 85.91% of accuracy) and regression (e.g., 0.462 of the correlation coefficient) performance, compared to all comparison methods. Moreover, our proposed method yields 76.97% of accuracy for predicting the severe cases, 0.524 of the correlation coefficient, and 0.55 days difference for the conversion time., Competing Interests: Declaration of Competing Interest F.S., Y.C., W.Z., M.L., L.W., Y.G., and D.S. are employees of Shanghai United Imaging Intelligence Co., Ltd. The company has no role in designing and performing the surveillances and analyzing and interpreting the data. All other authors report no conflicts of interest relevant to this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pharmaceutically active compounds (PhACs) have been frequently detected in aquatic environment and raised concerns because of their environmental persistence and potential ecological risk, especially carbamazepine (CBZ), erythromycin (ERY), atenolol (ATL) and clofibric acid (CA). The UV/H 2 O 2 advanced oxidation process was considered as an effective process to remove pharmaceuticals in wastewater. Because of the diverse structure of pharmaceuticals and the various wastewater matrices, this study established two models to predict the degradation of 4 PhACs in wastewater by UV/H 2 O 2 . Besides, the degradation pathway and toxicity of 4 PhACs by UV/H 2 O 2 were explored. The degradation of 4 PhACs by UV/H 2 O 2 followed the pseudo first-order kinetics pattern. The degradation rate of pharmaceuticals decreased as CBZ > ATL > CA > ERY. A kinetic model combining the steady state concentrations of HO∙ successfully predicted the degradation process of pharmaceuticals in 14 secondary municipal wastewater effluents. Also, a water matrix prediction model by response surface methodology (RSM) was established to estimate the degradation of pharmaceuticals well. A detailed and systematic comparison of two models in the objectives of models, predicting target contaminants, types of wastewater and parameters of models was made. In addition, the tentative transformation pathways of 4 PhACs by UV/H 2 O 2 were proposed. 4 PhACs after UV/H 2 O 2 treatment enhanced the toxicity, and prolongation of treatment time can reduce the toxicity on the luminescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Electroencephalograph (EEG) plays a significant role in the diagnostics process of epilepsy, but the detection rate is unsatisfactory when the length of interictal EEG signals is relatively short. Although the deliberate attacking theories for undirected brain network based on node removal method can extract potential network features, the node removal method fails to sufficiently consider the directionality of brain electrical activities. To solve the problems above, this study proposes a feature tensor-based epileptic detection method of directed brain networks. First, a directed functional brain network is constructed by calculating the transfer entropy of EEG signals between different electrodes. Second, the edge removal method is used to imitate the disruptions of brain connectivity, which may be related to the disorder of brain diseases, to obtain a sequence of residual networks. After that, topological features of these residual networks are extracted based on graph theory for constructing a five-way feature tensor. To exploit the inherent interactions among multiple modes of the feature tensor, this study uses the Tucker decomposition method to get a core tensor which is finally reshaped into a vector and input into the support vectors machine (SVM) classifier. Experiment results suggest that the proposed method has better epileptic screening performance for short-term interictal EEG data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Song, Huo, Ma, Ding, Wang, Dai and Huang.)