Genetic determinants of IgG antibody response to COVID-19 vaccination.

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRß1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review.

Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety.Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019).Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.

The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.

Potential electron acceptors for ammonium oxidation in wastewater treatment system under anoxic condition: A review.

Anaerobic ammonium oxidation has been considered as an environmental-friendly and energy-efficient biological nitrogen removal (BNR) technology. Recently, new reaction pathway for ammonium oxidation under anaerobic condition had been discovered. In addition to nitrite, iron trivalent, sulfate, manganese and electrons from electrode might be potential electron acceptors for ammonium oxidation, which can be coupled to traditional BNR process for wastewater treatment. In this paper, the pathway and mechanism for ammonium oxidation with various electron acceptors under anaerobic condition is studied comprehensively, and the research progress of potentially functional microbes is summarized. The potential application of various electron acceptors for ammonium oxidation in wastewater is addressed, and the N2O emission during nitrogen removal is also discussed, which was important greenhouse gas for global climate change. The problems remained unclear for ammonium oxidation by multi-electron acceptors and potential interactions are also discussed in this review.

RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.

The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1-H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial-temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability.

Perceived ambidextrous leadership and nurses' mental health: a work-family perspective.

BACKGROUND: Nurses are particularly at risk from stress-related problems and face high mental health problems during the COVID-19 pandemic. It is critical to pay attention to their mental health status and determine which factors are positively associated with nursing staff mental health from the perspective of work-family. The purpose of this paper is to investigate the impact of perceived ambidextrous leadership on nurses' mental health mediated by work-to-family enrichment and moderated by work climate for sharing family concerns. METHODS: One time-lagged study with three waves was conducted. A total of 358 questionnaires were distributed to registered nurses working at 10 hospitals in Guangzhou, China, and 265 valid questionnaires were returned. The quantitative approach to test hypotheses involves hierarchical regression analyses, the bootstrapping method and the simple slope test. RESULTS: The research indicated that (a) perceived ambidextrous leadership had a positive influence on nurses' work-to-family enrichment; (b) nurses' work-to-family enrichment mediated the relationship between perceived ambidextrous leadership and nurses' mental health; (c) work climate for sharing family concerns moderated the relationship between perceived ambidextrous leadership and nurses' work-to-family enrichment. CONCLUSION: Nursing supervisors' ambidextrous leadership interacted with work climate for sharing family concerns benefit the conservation of nurses' personal resources, which in turn facilitates nurses' work-to-family enrichment and improve their mental health.

Structural analysis of the ferric-binding protein KfuA from Klebsiella pneumoniae.

Iron acquisition is an essential process of cell physiology for biological systems. In Klebsiella pneumoniae, the siderophore and ferric-acquisition ABC (ATP-Binding-Cassette) transporter KfuABC is utilized for iron uptake. Initial recognition of the various ferric sources in periplasm and transportation across the cytoplasmic membrane is performed by the substrate-binding protein (SBP) KfuA. Here we report the 2.0 Å resolution crystal structure of KfuA from K. pneumoniae, which crystallizes in the space group P1211 with a single monomer in the asymmetric unit. A bound metal ion reveals the residues required for binding ferric ions. Binding analysis shows that ferric iron and the iron-mimicking gallium bind with high affinity to KfuA. Growth curves show that gallium inhibits growth of K. pneumoniae whereas ferric iron enhances it. This work suggests a mechanism whereby gallium effectively competes with ferric iron, disrupting iron-dependent biological functions via binding to KfuA and leading to heightened antimicrobial efficacy. Significantly, humans lack equivalent ABC transporters like SBP KfuA, underscoring the potential of KfuA as an attractive target for therapeutic intervention.

DNA Nanoflower Eye Drops with Antibiotic-Resistant Gene Regulation Ability for MRSA Keratitis Target Treatment.

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial keratitis is highly intractable, with strong resistance to ß-lactam antibiotics. Inhibiting the MRSA resistance gene mecR1 to downregulate penicillin-binding protein PBP2a has been implicated in the sensitization of ß-lactam antibiotics to MRSA. However, oligonucleotide gene regulators struggle to penetrate dense biofilms, let alone achieve efficient gene regulation inside bacteria cells. Herein, an eye-drop system capable of penetrating biofilms and targeting bacteria for chemo-gene therapy in MRSA-caused bacterial keratitis is developed. This system employed rolling circle amplification to prepare DNA nanoflowers (DNFs) encoding MRSA-specific aptamers and mecR1 deoxyribozymes (DNAzymes). Subsequently, ß-lactam antibiotic ampicillin (Amp) and zinc oxide (ZnO) nanoparticles are sequentially loaded into the DNFs (ZnO/Amp@DNFs). Upon application, ZnO on the surface of the nanosystem disrupts the dense structure of biofilm and fully exposes free bacteria. Later, bearing encoded aptamer, the nanoflower system is intensively endocytosed by bacteria, and releases DNAzyme under acidic conditions to cleave the mecR1 gene for PBP2a down-regulation, and ampicillin for efficient MRSA elimination. In vivo tests showed that the system effectively cleared bacterial and biofilm in the cornea, suppressed proinflammatory cytokines interleukin 1ß ï¼ˆIL-1ß） and tumor neocrosis factor-alpha （TNF-α）, and is safe for corneal epithelial cells. Overall, this design offers a promising approach for treating MRSA-induced keratitis.

Clinicopathological and mutational characteristics of primary double mutant gastrointestinal stromal tumor: a single center study with review of the literature.

AIMS: Primary double KIT/PDGFRA mutations are very rare in gastrointestinal stromal tumours (GISTs) but have not been comprehensively studied to date. In the present study, we investigated the clinicopathologic and genetic features of eight cases of primary double-mutant GISTs, and we reviewed the literature. METHODS AND RESULTS: The tumours occurred in six males and two females (age range 57-83 years) and involved the small intestine (n = 4), stomach (n = 2), rectum (n = 1) and retroperitoneum (n = 1). Clinical manifestations were variable, ranging from indolent (no symptoms) to aggressive disease (tumour rupture and haemorrhage). All patients underwent surgical excision, and six of them were treated with imatinib. No one experienced recurrence or other complications during the follow-up time (10 to 61 months). Histologically, all the tumours exhibited mixed cell types, accompanied by variable interstitial changes. KIT mutations were detected in all cases, and the majority of them were present in different exons (n = 5). No PDGFRA exon 12, 14 or 18 mutations were found. All the mutations were validated by next-generation sequencing, and two additional variants with comparatively low allelic fractions were identified in one case. Two of the cases had available allele distribution data, one with an in cis compound mutation and the other with an in trans compound mutation. CONCLUSION: Primary double-mutant GISTs have distinctive clinicopathologic and mutational features. Studies of more cases are necessary for a better understanding of these tumours.

Palladium-Catalyzed Chemodivergent Carbonylation of ortho-Bromoarylimine to Biisoindolinones and Spiroisoindolinones.

We herein report a palladium-catalyzed carbonylative cyclization reaction of ortho-bromoarylimines that allows for the chemodivergent synthesis of functionalized biisoindolinones and spirocyclic isoindolinones. Either product could be selectively obtained by switching the reaction temperatures and ligands, and the biisoindolinone products could be afforded facilely with catalyst loadings as low as 0.05 mol %. Further transformation of the biisoindolinone product is also described, which represents a novel and concise approach to the biisoindoline diamine ligand.

Variations in the impact of the new case-based payment reform on medical costs, length of stay, and quality across different hospitals in China: an interrupted time series analysis.

BACKGROUND: In 2018, an innovative case-based payment scheme called Diagnosis-Intervention Packet (DIP) was piloted in a large developed city in southern China. This study aimed to investigate the impact of the new payment method on total medical expenditure per case, length of stay (LOS), and in-hospital mortality rate across different hospitals. METHODS: We used the de-identified patient-level discharge data of hospitalized patients from 2016 to 2019 in our study city. The interrupted time series model was used to examine the impact of the DIP payment reform on inflation-adjusted total expenditure per case, LOS, and in-hospital mortality rate across different hospitals, which were stratified into different hospital ownerships (public and private) and hospital levels (tertiary, secondary, and primary). RESULTS: We included 2.08 million and 2.98 million discharge cases of insured patients before and after the DIP payment reform, respectively. The DIP payment reform resulted in a significant increase of the monthly trend of adjusted total expenditure per case in public (1.1%, P = 0.000), tertiary (0.6%, P = 0.000), secondary (0.4%, P = 0.047) and primary hospitals (0.9%, P = 0.039). The monthly trend of LOS increased significantly in public (0.022 days, P = 0.041) and primary (0.235 days, P = 0.032) hospitals. The monthly trend of in-hospital mortality rate decreased significantly in private (0.083 percentage points, P = 0.002) and secondary (0.037 percentage points, P = 0.002) hospitals. CONCLUSIONS: We conclude that implementing the DIP payment reform yields inconsistent consequences across different hospitals. DIP reform encouraged public hospitals and high-level hospitals to treat patients with higher illness severities and requiring high treatment intensity, resulting in a significant increase in total expenditure per case. The inconsistencies between public and private hospitals may be attributed to their different baseline levels prior to the reform and their different responses to the incentives created by the reform.

How do inpatients' costs, length of stay, and quality of care vary across age groups after a new case-based payment reform in China? An interrupted time series analysis.

CONTEXT: A patient classification-based payment system called diagnosis-intervention packet (DIP) was piloted in a large city in southeast China in 2018. OBJECTIVE: This study evaluates the impact of DIP payment reform on total costs, out-of-pocket (OOP) payments, length of stay (LOS), and quality of care in hospitalised patients of different age. METHODS: An interrupted time series model was employed to examine the monthly trend changes of outcome variables before and after the DIP reform in adult patients, who were stratified into a younger (18-64 years) and an older group (≥ 65 years), further stratified into young-old (65-79 years) and oldest-old (≥ 80 years) groups. RESULTS: The adjusted monthly trend of costs per case significantly increased in the older adults (0.5%, P = 0.002) and oldest-old group (0.6%, P = 0.015). The adjusted monthly trend of average LOS decreased in the younger and young-old groups (monthly slope change: -0.058 days, P = 0.035; -0.025 days, P = 0.024, respectively), and increased in the oldest-old group (monthly slope change: 0.107 days, P = 0.030) significantly. The changes of adjusted monthly trends of in-hospital mortality rate were not significant in all age groups. CONCLUSION: Implementation of the DIP payment reform associated with increase in total costs per case in the older and oldest-old groups, and reduction in LOS in the younger and young-old groups without deteriorating quality of care.

First Report of Lasiodiplodia pseudotheobromae causing Postharvest Decay of Strawberries in Florida.

Postharvest decay of strawberry (Fragaria × ananassa Duch.) is a major factor causing fruit losses. Strawberries were obtained from various harvests at cooling facilities located in Dover and Plant City, FL during the 2018-19 and 2019-20 seasons. After the fruits were incubated at 22ºC for up to 5 days (d) to promote disease development, Lasiodiplodia decay was observed at up to 3% from some harvests, exhibiting gray mycelia on small lesions that gradually covered the whole fruit. The fungus was isolated onto potato dextrose agar (PDA). Five isolates (SBD18-14, SBD18-277, SBD18-279, SBD19-02 and SBD19-57) were characterized. Fungal mycelia were initially grayish white and then gradually changed to gray to dark gray on PDA at 25oC, and later produced black pigments (Fig. S1). Pycnidia were observed from inoculated strawberries at 14 d. Isolates shared similar conidia morphology: aseptate, hyaline, ellipsoid to ovoid, measuring L × W: 24.0-34.0 (28.3) × 13.0-16.0 (14.3) µm (n =100). Mature conidia were brown, one septate, measuring L × W: 25.0-33.0 (28.8) × 13.0-16.0 (14.5) µm (n =100). The isolates were identified as Lasiodiplodia spp. morphologically (Alves et al. 2008). DNA was extracted from fungal mycelia using an OmniPrep DNA extraction kit, and PCR amplification of ITS and EF1-α genes was performed following the conditions described by White et al. (1990) with some modifications using primers ITS1F-F/ITS4-R (Gardes and Bruns, 1993; White et al., 1990) and EF1-668-F/EF1-1251-R (Alves et al., 2008), respectively. The BLASTn in GenBank showed that the sequences obtained had 99.61 to 100% homology with those of ITS (EF622077) and EF1-α (EF622057) from L. pseudotheobromae CBS116459 (an ex-type strain) (Alves et al., 2008). Sequences of the isolates have been deposited in GenBank with accessions OP326017 to OP326021 for ITS, and OP356202 to OP356206 for EF1-α. Phylogenetic analysis showed that these isolates clustered in the same clade (bootstrap value at 64) with L. pseudotheobromae (Fig. S2). Two fungal inoculum types (mycelia and conidia), two fruit inoculation methods (injury and non-injury) and five fungal isolates were used for pathogenicity tests. Fungal mycelia (2-day-old) on PDA plug (5 mm) or 10 µL of conidial suspension (106 spores/mL) was placed onto each injury (1 x 1 mm in size) or a non-injury area on the surfaces of five strawberry fruits (cv. Florida Brilliance). PDA plug alone or water drops placed on injury or non-injury areas on fruits served as respective controls. Inoculated and control fruits were incubated in a covered plastic container with 100% RH at 22ºC. The experiment was repeated twice. Decay initially appeared as soft and lightly discolored tissue at inoculation areas 2 d post-inoculation (dpi) that extended quickly thereafter. Brown to dark lesions on both injury- and non-injury fruits inoculated with conidia or mycelia were observed at 3 dpi. Decay and gray mycelia gradually developed over the whole fruit at 6 dpi, and pycnidia were observed after 14 dpi (Fig. S1). Disease incidence of 100% was observed on all tests. Control fruits did not develop decay. The results indicate that these isolates are pathogenic to strawberries and infect fruit via both non-injured and injured fruit surfaces. The inoculated fungal isolates were re-isolated, thus, fulfilling Koch's postulates. L. theobromae, Neofusicoccum parvum/N. ribis species complex causing strawberry fruit rot in Florida fields was reported (Oliveira et al., 2019), but not L. pseudotheobromae. To our knowledge, this is the first report of postharvest decay caused by L. pseudotheobromae A.J.L. Phillips, A. Alves & Crous on strawberries in Florida and in the USA, and it should be considered in strawberry disease management.

In Situ Decoration of Bi2S3 Nanosheets on Zinc Oxide/Cellulose Acetate Composite Films for Photodegradation of Dyes under Visible Light Irradiation.

A novel Bi2S3-zinc oxide/cellulose acetate composite film was prepared through a blending-wet phase conversion and in situ precipitate method. The results revealed that the incorporation of Bi2S3 in the film increased the cavity density and uniformity, which provided additional space for the growth of active species and improved the interaction between dye pollutants and active sites. Zinc oxide acted as a mediator to facilitate the separation of electron-hole pairs effectively preventing their recombination, thus reducing the photo-corrosion of Bi2S3. As a result, the Bi2S3-ZnO/CA composite film exhibited favorable photocatalytic activity in the degradation of various dyes. Additionally, the composite film displayed effortless separation and recovery without the need for centrifugation or filtration, while maintaining its exceptional catalytic performance even after undergoing various processes.

A Novel Compute-and-Forward Relaying Method for Multi-Antenna Wireless Relay Networks.

Compute-and-Forward (CoF) is an innovative physical layer network coding strategy, designed to enable receivers in wireless communications to effectively utilize interference. The key idea of CoF is to implement integer combinations based on the codewords from multiple transmitters, rather than decoding individual source codewords. Although CoF is widely used in wireless relay networks, there are still some problems to be solved, such as rank failure, single antenna reception, and the shortest vector problem. In this paper, we introduce a successive extended CoF (SECoF) as a pioneering solution tailored for multi-source, multi-relay, and multi-antenna wireless relay networks. First, we analyze the traditional CoF, and design a SECoF method combining the concepts of matrix projection and successive interference cancellation, which overcomes the problem of CoF rate tending to zero and rank failure and improves the network performance. Secondly, we obtain an approximate solution to the integer-value coefficient vectors by using the LLL lattice-based resolution algorithm. In addition, we deduce the corresponding concise formulas of SECoF. Simulation results show that the SECoF has strong robustness and the approaches outperform the state-of-the-art methods in terms of computation rate, rank failure probability, and outage probability.

Structural characterization of the novel stress response facilitator (SrfA) from Pseudomonas aeruginosa.

Chronic pulmonary infections in those living with cystic fibrosis or chronic obstructive pulmonary disease are promoted by production of alginate by the opportunistic pathogen Pseudomonas aeruginosa. Alginate biosynthesis enzymes in P. aeruginosa are regulated by the extracytoplasmic function alternative sigma factor σ22 either by mutation in mucA or in response to envelope stress. An intergenic region between ORFs PA2559 and PA2560 in P. aeruginosa is σ22-dependent and its transcription is activated by cell wall stress. This stress-responsive transcript encodes a novel stress response facilitator, SrfA, that is exclusively conserved only in P. aeruginosa species. Here we report the first three-dimensional structure of SrfA determined by molecular replacement using fold prediction to generate a search model. The SrfA structure adopts a helix-loop-helix fold that shares some similarity with structures of anti-activator or effector proteins. A ΔsrfA mutant strain of P. aeruginosa PAO1 exhibited significantly reduced biofilm formation, which was restored to wild-type levels when ΔsrfA was complemented with srfA. The ΔsrfA strain also exhibited increased sensitivity to macrolide antibiotics. We further show using MicroScale Thermophoresis that SrfA interacts with both PA2559 and PA2560 with high affinity. This work provides a starting point for further investigation into the role of SrfA in response to cell wall stress.

SnRK2 subfamily I protein kinases regulate ethylene biosynthesis by phosphorylating HB transcription factors to induce ACO1 expression in apple.

Ethylene (ETH) controls climacteric fruit ripening and can be triggered by osmotic stress. However, the mechanism regulating ETH biosynthesis during fruit ripening and under osmotic stress is largely unknown in apple (Malus domestica). Here, we explored the roles of SnRK2 protein kinases in ETH biosynthesis related to fruit ripening and osmoregulation. We identified the substrates of MdSnRK2-I using phosphorylation analysis techniques. Finally, we identified the MdSnRK2-I-mediated signaling pathway for ETH biosynthesis related to fruit ripening and osmoregulation. The activity of two MdSnRK2-I members, MdSnRK2.4 and MdSnRK2.9, was significantly upregulated during ripening or following mannitol treatment. Overexpression of MdSnRK2-I increased ETH biosynthesis under normal and osmotic conditions in apple fruit. MdSnRK2-I phosphorylated the transcription factors MdHB1 and MdHB2 to enhance their protein stability and transcriptional activity on MdACO1. MdSnRK2-I also interacted with MdACS1 and increased its protein stability through two phosphorylation sites. The increased MdACO1 expression and MdACS1 protein stability resulted in higher ETH production in apple fruit. In addition, heterologous expression of MdSnRK2-I or manipulation of SlSnRK2-I expression in tomato (Solanum lycopersicum) fruit altered fruit ripening and ETH biosynthesis. We established that MdSnRK2-I functions in fruit ripening and osmoregulation, and identified the MdSnRK2-I-mediated signaling pathway controlling ETH biosynthesis.

Pd-Catalyzed carbonylative lactonization of 2-halidearomatic aldehydes with H2O as a nucleophile.

A palladium-catalyzed carbonylative cyclization reaction of 2-halidebenzaldehydes with H2O is described, which provides a strategy for the synthesis of diversely substituted 3,3'-oxyphthalides. Notably, the obtained 3,3'-oxyphthalide could be easily transformed into 3-aryl and alkyl phthalides with excellent efficiency using organozinc reagents under mild reaction conditions.

Prediction of Maximum Absorption Wavelength Using Deep Neural Networks.

Fluorescent molecules are important tools in biological detection, and numerous efforts have been made to develop compounds to meet the desired photophysical properties. For example, tuning the wavelength allows an appropriate penetration depth with minimal interference from the autofluorescence/scattering for a better signal-to-noise contrast. However, there are limited guidelines to rationally design or computationally predict the optical properties from first principles, and factors like the solvent effects will make it more complicated. Herein, we established a database (SMFluo1) of 1181 solvated small-molecule fluorophores covering the ultraviolet-visible-near-infrared absorption window and developed new machine learning models based on deep neural networks for accurately predicting photophysical parameters. The optimal system was applied to 120 out-of-sample compounds, and it exhibited remarkable accuracy with a mean relative error of 1.52%. In this new paradigm, a deep learning algorithm is promising to complement conventional theoretical and experimental studies of fluorophores and to greatly accelerate the discovery of new dyes. Due to its simplicity and efficiency, data from newly developed fluorophores can be easily supplemented to this system to further improve the accuracy across various dye families.

Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1 mg kg-1 DOX with 5 mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Morphological Studies of Solution-Crystallized Thermoplastic Elastomers with Polyethylene Endblocks and a Random-Copolymer Midblock.

Styrenic thermoplastic elastomers (TPEs) in the form of triblock copolymers possessing glassy endblocks and a rubbery midblock account for the largest global market of TPEs worldwide, and typically rely on microphase separation of the endblocks and the subsequent formation of rigid microdomains to ensure satisfactory network stabilization. In this study, the morphological characteristics of a relatively new family of crystallizable TPEs that instead consist of polyethylene endblocks and a random-copolymer midblock composed of styrene and (ethylene-co-butylene) moieties are investigated. Copolymer solutions prepared at logarithmic concentrations in a slightly endblock-selective solvent are subjected to crystallization under different time and temperature conditions to ascertain if copolymer self-assembly is directed by endblock crystallization or vice versa. According to transmission electron microscopy, semicrystalline aggregates develop at the lowest solution concentration examined (0.01 wt%), and the size and population of crystals, which dominate the copolymer morphologies, are observed to increase with increasing aging time. Real-space results are correlated with small- and wide-angle X-ray scattering to elucidate the concurrent roles of endblock crystallization and self-assembly of these unique TPEs in solution.