ß-Cyclodextrin Polymer-Based Fluorescence Enhancement Strategy via Host-Guest Interaction for Sensitive Assay of SARS-CoV-2.

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that ß-cyclodextrin polymer (ß-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host-guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host-guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3' terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host ß-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of ß-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

Novel rare variants in FGFR1 and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients.

OBJECTIVE: We aimed to analyse FGFR1 rare variants in a series of Chinese congenital hypogonadotropic hypogonadism (CHH) patients. In addition, we intended to understand the clinical characteristics and the response to treatment of CHH patients with FGFR1 rare variants. PATIENTS AND METHODS: A total of 357 CHH patients were recruited at Peking Union Medical College Hospital. We used Sanger sequencing to analyse FGFR1 gene. In silico analysis was carried out to study the pathogenicity of novel missense variants. The clinical, endocrinological and therapeutic effects from patients carrying FGFR1 rare variants were analysed retrospectively. RESULTS: Thimissense mutations.rty patients in this series were found to harbour 29 FGFR1 rare variants, with 8 recurrent and 21 novel variants. After comprehensive analysis, 18 out of 21 novel variants were classified as likely pathogenic (LP) ones. These variants are widely spread throughout the FGFR1 gene and almost all FGFR1 functional domains, which exhibited no hot spot. Cryptorchidism, cleft palate and dental abnormality incidence in this CHH series that possessed FGFR1 LP variants were approximately 38.5%, 7.6% and 3.8%, respectively. Among patients who accepted the fertility-promoting treatment, 8 out of 10 patients succeeded in spermatogenesis. CONCLUSIONS: Eighteen novel LP variants were found to expand the spectrum of FGFR1 rare variants. In CHH patients possessing FGFR1 variants, we found that the rate of spermatogenesis was high following fertility-promoting therapy and the existence of cryptorchidism may represent the underlying factors which affect spermatogenesis.

[Association of the extra-gonadal manifestations with different pathogenic gene mutations in male patients with congenital hypogonadotropic hypogonadism].

OBJECTIVE: To explore the relationships between pathogenic gene mutations and extra-gonadal manifestations in male patients with congenital hypogonadotropic hypogonadism (CHH). METHODS: A total of 15 genes were screened in 259 CHH patients by massively parallel DNA sequencing. The identified pathogenic mutations were confirmed by Sanger polymerase chain reaction (PCR). The extra-gonadal features in all patients were recorded. RESULTS: Gene mutations were detected in 83 (32.0%) patients, which included FGFR1 (n=20), PROKR2 (n=19), CHD7 (n=16), KAL1 (n=14) and other genes (n=14), such as PROK2, FGF8, GNRHR, KISS1R, NELF and WDR11. Patients with KAL1 mutation displayed CHH related family history (n=5) and obesity (n=3). Patients with FGFR1 mutation presented with short stature (n=3), testicular hydrocele (n=2), lip-palate cleft (n=2) and dental dysplasia (n=1). Patients without detectable mutations may also exhibit obesity, mental retardation and short stature. CONCLUSIONS: CHH patients may present with extra-gonadal manifestations, including anosmia, obesity, dental dysplasia, short stature and mental retardation. An obscure relationships could be found between the clinical features and different gene mutations, but it is difficult to speculate the types of pathogenic gene mutations according to these extra-gonadal manifestations.

Macrophage-Inspired marine antifouling coating with dynamic surfaces based on regulation of dynamic covalent bonds.

Macrophages can kill bacteria and viruses by releasing free radicals, which provides a possible approach to construct antifouling coatings with dynamic surfaces that release free radicals if the breaking of dynamic covalent bonds is precisely regulated. Herein, inspired by the defensive behavior of macrophages of releasing free radicals to kill bacteria and viruses, a marine antifouling coating composed of polyurethane incorporating dimethylglyoxime (PUx-DMG) is prepared by precise regulation of dynamic oxime-urethane covalent bonds. The obtained alkyl radical (R·) derived from the cleavage of the oxime-urethane bonds manages to effectively suppress the attachment of marine biofouling. Moreover, the intrinsic dynamic surface makes it difficult for biofouling to adhere and ultimately achieves sustainable antifouling property. Notably, the PU50-DMG coating not only presents efficient antibacterial and antialgae properties, but also prevents macroorganisms from settling in the sea for up to 4 months. This provides a pioneer broad-spectrum strategy to explore the marine antifouling coatings.

The efficacy and cardiac toxicity of different-dose pegylated liposomal doxorubicin in elderly patients with diffuse large B lymphoma.

OBJECTIVES: In order to explore the impact of pegylated liposomal doxorubicin (PLD) dose intensity on survival outcomes of newly diagnosed elderly patients with diffuse large B-cell lymphoma (DLBCL), we performed a retrospective study to compare the efficacy and adverse effects of RCEOP (70 mg/m2 ), RCdOP (20-30 mg/m2 ) and RCDOP (30-45 mg/m2 ). The optimal PLD dose of patients with different clinical characteristics of subgroups was explored to provide a clue for the selection of clinical PLD dose. METHODS: A total of 335 DLBCL patients (60-85 years old) who were newly diagnosed and completed at least four cycles of RCE(D)OP were selected. The patients were mainly divided into RCEOP (126 cases) (epirubicin 70 mg/m2 ), RCdOP (151 cases) (PLD 20-30 mg/m2 ) and RCdOP (58 cases) (PLD 30-45 mg/m2 ). The effects of different doses of PLD on clinical efficacy, cardiotoxicity and prognosis of patients were retrospectively analyzed. Subgroup analysis was performed to compare the clinical characteristics of different subgroups. RESULTS: Our study showed that PLD and epirubicin had similar efficacy (overall survival (OS) p = 0.776; progression-free survival (PFS) p = 0.959). RCDOP (30-45 mg/m2 PLD) group had a higher complete remission (CR) rate of 75.9% compared with RCdOP (20-30 mg/m2 PLD) group (P D vs. d = 0.018). In the overall population, there was no significant difference in survival between RCDOP and RCdOP groups (OS P D vs. d = 0.661; PFS P D vs. d = 0.212). In patients with underlying cardiovascular diseases, the PFS of the RCDOP group was significantly better than the RCdOP group (p = 0.043). Meanwhile, patients in the RCDOP group tended to have a better prognosis than those in the RCEOP group (OS: RCDOP vs. RCEOP p = 0.054, PFS: RCDOP vs. RCEOP p = 0.053). There was no significant difference in the incidence of cardiotoxicity and other adverse events among the three groups. For the low-risk (age-adjusted-International Prognostic Index = 0/1) old patients without cardiovascular disease, RCdOP was considered a better strategy in OS (p = 0.020). CONCLUSION: In the general population, the CR rate in the RCDOP group was significantly higher than that in the RCdOP group (p = 0.018). For elderly DLBCL patients with cardiovascular disease, the effect benefit brought by the PLD dose was more obvious, and the PFS of the RCDOP group was significantly better than that of the RCdOP group (p = 0.043). Full dose of PLD is an efficient alternative in the treatment of patients with preexisting cardiovascular diseases.

Surface morphology properties and antifouling activity of Bi2WO6/boron-grafted polyurethane composite coatings realized via multiple synergy.

An inorganic-organic composite coating is an effective way to solve the issue of marine organism attachment and realize multi-element synergistic antifouling. Herein, Bi2WO6/boron-grafted polyurethane composite coatings (BWOB) composed of Bi2WO6 with three morphologies (nanosheet, flower and microsphere) and boron-grafted polyurethane (ITB) were successfully synthesized to achieve high-efficiency antifouling. Bi2WO6 nanoparticles were evenly distributed on the surface and inside the ITB to form micro/nanostructures. In the composite coatings doped with flower-shaped Bi2WO6, BWOB-5 showed excellent antibacterial and antidiatom adhesion properties, achieving 95.43% and 98.38% against Escherichia coli and Staphylococcus aureus, respectively, and 98.62% against Nitzschia closterium. In addition, the micro/nanostructure on the surface, the stable production of hydroxyl radicals (·OH) and superoxide radicals (·O2-) during photocatalysis, and the antifouling functional groups of the resin matrix in the BWOB composite coatings were all conducive to photocatalytic antifouling activity. More importantly, BWOB coatings exhibited excellent environmentally friendly properties. Therefore, BWOB coatings are expected to have potential application value in the field of photocatalytic sterilization and antifouling.

Constructing an Amino-reinforced amidoxime swelling layer on a Polyacrylonitrile surface for enhanced uranium adsorption from seawater.

Polyacrylonitrile (PAN)-based materials have been studied for decades as uranium (U(VI)) adsorbents, because the further products of abundant nitrile groups, amidoxime (AO) groups, show great affinity for U(VI) ions. However, excessive amidoximation could cause the shrinkage of PAN fibers, resulting in decreased adsorption performance. Hence, an amino-reinforced amidoxime (ARAO) swelling layer was constructed on the PAN fiber surface (PAN-NH2-AO) by modification of the strongly hydrophilic amino group to prevent shrinkage. The molecular chains in the ARAO swelling layer would be swelled due to the adsorption of a large amount of water. Simultaneously, U(Ⅵ) ions can penetrate into the ARAO swelling layer with water molecules and coordinate with amino or AO groups, leading to increased adsorption performance. PAN-NH2-AO exhibited maximum U(VI) and water adsorption capacities of 492.61 mg g-1 and 20.32 g g-1 at 25 â„ƒ with a swelling ratio of 20.73%, respectively. The adsorption capacity of PAN-NH2-AO was 0.312 mg g-1 after a 91-day immersion in Yellow Sea, China. The study of the adsorption thermodynamics and kinetics of PAN-NH2-AO showed that the adsorption process was spontaneous homogeneous chemical adsorption. This paper proposes a novel method to obstruct amidoximation induced shrinkage and to maximize the potential application of PAN-based materials.

Synergistically Improved Antifouling Efficiency of a Bioinspired Self-renewing Interface via a Borneol/ Boron Acrylate Polymer.

Underwater facilities are often perplexed by severe and ubiquitous biofouling. The widely applied commercial antifouling materials still have several challenges in static applications. Herein, a polymer containing isoborneol and borane (PBABs), the borneol derivative structure and grafted pyridine-triphenylborane (PTPB) as antifouling groups were prepared by radical polymerization. PBABs showed high antibacterial rates for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of up to 95.1% and 81.1%, respectively, confirming superior antibacterial adhesion propertys. More importantly, PBABs effectively reduced the expression of mussel adhesion protein, indicating superior antifouling propertys, resulting from the synergistic effect of multiple antifouling functional groups on the material's surface. Therefore, the PBABs have been evaluated as noncytotoxic, low-cost, easily synthesized, and mass-produced, which demonstrates their great potential for actual marine applications.

Bioinspired Durable Antibacterial and Antifouling Coatings Based on Borneol Fluorinated Polymers: Demonstrating Direct Evidence of Antiadhesion.

Substituting natural products for traditional poison-killing antifouling agents is an efficient and promising method to alleviate the increasingly serious ecological crisis and aggravate the loss due to marine biofouling. Herein, the successful synthesis of poly(methyl methacrylate-co-ethyl acrylate-co-hexafluorobutyl methacrylate-co-isobornyl methacrylate) copolymer (PBAF) with borneol monomers and fluorine by a free radical polymerization method is reported. The PBA0.09F coating exhibits outstanding antibacterial and antifouling activity, achieving 98.2% and 92.3% resistance to Escherichia coli and Staphylococcus aureus, respectively, and the number of Halamphora sp. adhesion is only 26 (0.1645 mm2) in 24 h. This remarkable antibacterial and antifouling performance is attributed to the incorporation of fluorine components into the copolymer, which induces a low surface energy and hydrophobicity and the complex molecular structure of the natural nontoxic antifouling agent borneol. In addition, the results showed that the contents of the adhesion-related proteins mfp-3, mfp-5, and mfp-6 were significantly reduced, which proved that natural substances affect the secretion of biological proteins. Importantly, the PBAF coating exhibits excellent environmental friendliness and long-term stability. The antifouling mechanism is clarified, and an effective guide for an environmentally friendly antifouling coating design is proposed.

Swollen-layer constructed with polyamine on the surface of nano-polyacrylonitrile cloth used for extract uranium from seawater.

In this study, a swelling layer was constructed on the surface of the nano-polyacrylonitrile (PAN) fiber fabric prepared by electrospinning to enrich uranium (U (VI)) adsorption from seawater. The constructed swelling layer composes of a polyethyleneimine (PEI) containing a huge amount of amino groups and imino groups with strong hydrophilicity. The molecular chain swelled in an aqueous solution by forming a swelling layer on the PAN surface. In addition, p-aminobenzenesulfonic acid (SA) was used as the side chain end group grafted on the PAN surface, the benzene ring as the side chain can hinder the rotation of the PEI chain, thereby increasing the rigidity. The increasing of the rigidity leads to stretch the conformation of the PEI molecular chain, increasing the probability of collision with U (VI), which is beneficial for adsorption. The adsorption capacity of the prepared adsorbent in the adsorption experiment reached 215.25 mg g-1, and the adsorption capacity in the 8 ppm spiked simulated seawater reached 144.5 mg g-1. The adsorption mechanism of U (VI) was analyzed by XPS. The sulfonic acid group in SA as the terminal group and amino group in the swelling layer formed a coordination structure with U (VI). The swelling layer constructed on the surface of polyacrylonitrile fibers is used to effectively extract uranium from seawater.

Superhydrophobic nanoporous polymer-modified sponge for in situ oil/water separation.

Developing an efficient and environmentally friendly strategy for oil-water separation is extremely important for practical application. In this study, a superhydrophobic and superoleophilic melamine sponge loaded with cross-linked and swellable polydivinylbenzene was successfully fabricated by a facile and effective one-step impregnation-curing method with adhesion of polydimethylsiloxane. The prepared sponge not only exhibited high oil absorption capacity, but it also enabled rapid oil collection in situ, which could be extended to practical application. Moreover, the modified superhydrophobic sponge showed excellent mechanical resistance and chemical stability. The surface morphology and chemical composition were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. This material has great development potential for large-scale oil spill clean-up and chemical spill accidents.

Three-dimensional flower-like shaped Bi5O7I particles incorporation zwitterionic fluorinated polymers with synergistic hydration-photocatalytic for enhanced marine antifouling performance.

Herein, several novel composite films consisting of three-dimensional (3D) Bi5O7I flower-like shaped microsphere and zwitterionic fluorinated polymer (ZFP) were successfully fabricated with the aim of achieving high anti-fouling performance. The prepared Bi5O7I flower-like shaped microsphere particles with diameters in the range of 2∼3 µm were uniformly distributed on the surface and in the internal of ZFP. Benefiting from the hydration layer formed by the ZFP and the efficient photocatalytic performance of Bi5O7I flower-like microsphere, the resultant optimized Bi5O7I/ZFP composite film exhibited an excellent diatom anti-settling performance and a high antibacterial rate of 99.09% and 99.66% towards Escherichia coli and Staphylococcus aureus. In addition, the composite films possessed the strengthened visible light absorption, the effectively separation and transfer of the photo-induced electrons and holes, the large number of hydroxyl (OH) radicals and superoxide radicals (O2-) all in Bi5O7I/ZFP systems, all of which were beneficial for the photocatalytic antifouling activity. More importantly, the synergistic hydration-photocatalytic effect of the Bi5O7I/ZFP composite films are answerable for the improvement of the antifouling property compared to the control. Thus, the synergistic hydration-photocatalytic contribution of Bi5O7I/ZFP composite film will shows promise for potential application in marine antifouling.

Light-responsive polymersomes with a charge-switch for targeted drug delivery.

Unlike the traditional block amphiphilic polymersomes, we herein report a lipid-like amphiphilic polymer that self-assembles into photo-responsive polymersomes for drug delivery. The introduction of a quaternary ammonium moiety not only provides a hydrophilic segment of the polymersomes, but also enables electrostatic adsorption with folic acid, thus achieving the targeting of cancer cells with overexpression of folate receptor. Upon light irradiation, the photocleavage reaction of the o-nitrobenzyl moiety disintegrates polymersomes by changing the polymer structure from cationic amphiphilic state to zwitterionic hydrophilic state, thus realizing photo-triggered drug release. The data showed that anticancer drugs (doxorubicin hydrochloride, DOX·HCl) can be loaded into the hydrophilic cavity of polymersomes and controllably released by photo-induced disintegration of polymersomes. Cellular assay showed that the active targeting of folic acid and photo-triggered release endowed the DOX-loaded polymersomes with a higher cytotoxicity to HeLa cells. Such cationic polymersomes provide a novel strategy for designing effective and intelligent drug carriers, and have potential application as a novel integrated platform for targeted drug delivery.

Antibacterial activity, cytotoxicity and mechanical behavior of nano-enhanced denture base resin with different kinds of inorganic antibacterial agents.

Silanized aluminum borate whiskers (ABWs) of 4 wt%, silanized zirconium dioxide nanoparticles (nano-ZrO2) of 2 wt% were mixed with polymethyl methacrylate (PMMA) powder to get ZrO2-ABWs/PMMA composites. Titanium dioxide (TiO2), silver-supported titanium dioxide (Ag/TiO2), silver-supported zirconium phosphate (Novaron) and tetrapod-like zinc oxide whiskers (T-ZnOw) antibacterial agents of 3 wt% were mixed with ZrO2-ABWs/PMMA composites respectively to fabricate standard specimens. Plaque biofilms on the specimens surface were investigated for colony-forming units (CFUs). In addition, cytotoxicity and mechanical behavior were evaluated. Results showed that the CFUs values of S. mutans and C. albican biofilms on the four antibacterial composites surface were all reduced (p<0.05) compared to the blank and control groups. The antibacterial composites did not have an adverse effect on fibroblast growth in this study (p>0.05) except TiO2 and Ag/TiO2 groups of undiluted extracts. The flexural strength and surface hardness of Novaron and T-ZnOw groups were increased (p<0.05) compared to the control group.

Hybrid effects of zirconia nanoparticles with aluminum borate whiskers on mechanical properties of denture base resin PMMA.

The aim of this study was to investigate the hybrid effects of ZrO2 nanoparticles (nano-ZrO2) and aluminum borate whiskers (ABWs) on flexural strength and surface hardness of denture base resin, polymethyl methacrylate (PMMA). Both nano-ZrO2 and ABWs were modified by silane coupling agent (Z6030) before being mixed with PMMA. Various amounts of silanized nano-ZrO2 and ABWs were mixed with PMMA to prepare ZrO2-ABW/PMMA composites. Flexural strength and surface hardness were evaluated using three- point bending test and Vickers hardness test respectively. Fractured surfaces were also observed by scanning electron microscopy (SEM). The mechanical behaviors of silanized ZrO2-ABW/PMMA composites were significantly improved. Flexural strength reached a maximum value of 108.01 ± 5.54 MPa when 2 wt% of nano-ZrO2 was mixed with ABWs at a ZrO2/ABW ratio of 1:2, amounting to an increase of 52% when compared with pure PMMA. Surface hardness achieved a maximum value of 22.50 ± 0.86 MPa when 3 wt% of nano-ZrO2 was mixed with ABWs at the same ZrO2/ABW ratio, which was an increase of 27% when compared with pure PMMA.