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In the era of advanced wearable electronic devices, the triboelectric nanogenerators (TENGs) as energy harvesting and self-powered sensing units hold great promise. Selecting appropriate triboelectric material is the crucial factor to optimize the performance of TENG, while polytetrafluoroethylene (PTFE) stands out as a highly versatile option among the various materials. In this study, we present an ultrafine nanofibrous PTFE (NF-PTFE) films prepared by novel in-situ fibrillation strategy as the triboelectric material in TENG devices. The innovative processing methodology facilely addresses the dilemma between high porosity and fine pore size of traditional porous PTFE films, meanwhile achieves exceptional mechanical strength, hydrophobicity, air permeability, and chemical resistance of the films. With the integration of nanofibrous PTFE films into contact-separation mode TENG and droplet-based TENG, these devices realize the peak electrical output of 131 V/10.8 µA and 54 V/14 µA with great durability, which surpass the performance of TENGs using traditional expanded PTFE films. Furthermore, a smart glove capable of recognizing hand gestures is proposed, which demonstrates the versatility, flexibility, and practicality of this material for potential use in smart devices. This reported NF-PTFE film provides insights for the design of high-performance TENG device for advanced wearable electrical applications. [ABSTRACT FROM AUTHOR]

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases. [ABSTRACT FROM AUTHOR]

Under the background of a transformation of the global energy structure, coal gasification technology has a wide application prospect, but its by-product, the coal gasification residue (CGR), is still not being efficiently utilized for recycling. The CGR contains abundant carbon components, which could be applied to the microwave absorption field as the carbon matrix. In this study, Fe/CGR composites are fabricated via a two-step method, including the impregnation of Fe3+ and the reduction process. The influence of the different loading capacities of the Fe component on the morphology and electromagnetic properties is studied. Moreover, the loading content of Fe and the surface morphology of the Fe/CGR can be reasonably controlled by adjusting the concentration of the ferric nitrate solution. Meanwhile, Fe particles are evenly inserted on the CGR framework, which expands the Fe/CGR interfaces to enhance interfacial polarization, thus further improving the microwave-absorbing (MA) properties of composites. Particularly, as the Fe3+ concentration is 1.0 mol/L, the Fe/CGR composite exhibits outstanding performance. The reflection loss reaches −39.3 dB at 2.5 mm, and the absorption bandwidth covers 4.1 GHz at 1.5 mm. In this study, facile processability, resource recycling, appropriately matched impedance, and excellent MA performance are achieved. Finally, the Fe/CGR composites not only enhance the recycling of the CGR but also pioneer a new path for the synthesis of excellent absorbents. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis. [ABSTRACT FROM AUTHOR]

With the increasingly severe electromagnetic interference issue and the huge heat dissipation demand caused by the miniaturized and integrated electronic devices, exploring the heat-conduction microwave absorption (MA) materials is highly desired and remains a great challenge. Herein, we reported the fabrication of ZnO/amorphous carbon (ZnO/AC) hybrid films covered on the surface of graphene (ZnO/AC/Graphene) to simultaneously apply as the MA and thermal management materials. The ZnO/AC coatings synthesized with the auxiliary of an atomic layer deposition (ALD) method are highly uniform and controllable, which can significantly improve the MA performance and thermal conduction properties of graphene. The reflection loss (RL) of −55.4 dB and the effective absorption bandwidth of 5.3 GHz were achieved with thickness of 2.0 mm for ZnO/AC/Graphene at a low loading content (3 wt.%). The minimum RL of −57.9 dB can be obtained in the ZnO/AC/Graphene composites at a low frequency (7.8 GHz). Moreover, the absorption frequency can be regulated by changing the ZnO/AC which can be readily implemented by adjusting the ALD cycles of ZnO. The thermal conductivity of ZnO/AC/Graphene is up to 257.8 mW·m−1·K−1, increased by 53.2% compared with natural rubber. The enhancement mechanisms of microwave loss and heat conduction are systematically studied in detail. This work not only develops an excellent candidate, but also provides a novel strategy to design functional materials for heat-conduction MA application. [ABSTRACT FROM AUTHOR]

Tuning the nanostructure of anode material is one of the most effective ways to promote energy storage performance in the field of lithium-ion batteries. Herein, two-dimensional (2D) MoNb12O33 (MNO) material synthesized by combining a hydrothermal method and high-temperature calcination treatment is reported as a potential candidate anode material for lithium-ion batteries. Compared with other niobium-based oxide, Mo has higher valence and higher conductivity, which is very beneficial for maintaining its own good electrochemical performance. The sheet-like structure with abundant holes is favorable for the sufficient connection between MNO nanoparticles and electrolyte, further enhancing the kinetics of the lithium-ion diffusion process, thus giving rise to even better electrochemical performance. Benefitting the elegant structure, the charge–discharge capacity of MNO is maintained separately at 60.74 mA h g−1 and 61.26 mA h g−1 after 1000 cycles at 10 C, and the coulomb efficiency is close to 100%. The lamellar MNO fabricated by the facile method in this work displays great promise for application in lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies. [ABSTRACT FROM AUTHOR]

A novel hollow HAp microflower with hierarchical mesoporous structure was designed through biomolecules induction and explored as macromolecular drug carrier. It is found that biomolecules play a vital role in the formation of hollow morphology and the construction of hierarchical mesoporous structure, which could remarkably improve the specific surface area of microflowers. Moreover, the microflowers display a higher drug loading capacity (263 ± 7.2 mg/g), sustained release behavior and exhibit a better biocompatibility in the cytotoxicity test, suggesting the microflowers can be regarded as a promising candidate in macromolecular drug delivery fields. In addition, it is proved that the excellent drug delivery property is attributed not only to the interaction among carrier, drug and medium environment but also to the pore structure and morphology of carrier. Over all, the work represents a versatile, new route toward the preparation of hollow HAp-based macromolecular drug carrier with hierarchical mesoporous structural features and provides new insight into the optimization of macromolecular drug delivery performance. [ABSTRACT FROM AUTHOR]

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%–18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Yolk-shell-structured calcium phosphate microspheres have a great potential for medical applications due to their excellent physicochemical properties and biocompatibility. However, developing a yolk-shell-structured calcium phosphate with high adsorption capability remains a challenge. Herein, a porous yolk-shell-structured microsphere (ATP-CG) of calcium phosphate with high-specific surface area [SBET = 143 m2 g−1, which is approximately three times as high as that of ATP-CL microspheres synthesized by replacing calcium source with calcium l-lactate pentahydrate (CL)] was successfully synthesized by using adenosine 5'-triphosphate disodium salt (ATP) as the phosphorous source and calcium gluconate monohydrate (CG) as calcium source through a self-templating approache. The influences of molar ratio of Ca to P (Ca/P), hydrothermal temperature, and time on the morphology of ATP-CG microspheres were also investigated. It is found that the organic calcium source and organic phosphorous source play a vital role in the formation of yolk-shell structure. Furthermore, a batch of adsorption experiments were investigated to illuminate the adsorption mechanism of two kinds of yolk-shell-structured microspheres synthesized with different calcium sources. The results show that the adsorption capacity of ATP-CG microspheres (332 ± 36 mg/g) is about twice higher than that of ATP-CL microspheres (176 ± 33 mg/g). Moreover, the higher-specific surface area caused by the calcium source and unique surface chemical properties for ATP-CG microspheres play an important role in the improvement of HEL adsorption capability. The study indicates that the as-prepared yolk-shell-structured microsphere is promising for application in drug delivery fields and provides an effective approach for improving drug adsorption capability. [ABSTRACT FROM AUTHOR]

Streptococcus suis (S. suis) is one of the most common swine pathogens in the swine industry and leads to great harm to the normal progress of the swine industry. S. suis can also infect humans and cause a variety of fatal diseases, such as meningitis and streptococcal toxic shock syndrome, that pose a major threat to the safety of life and health of both humans and animals. In this paper, we found that isorhamnetin, a natural flavonoid compound without activity against S. suis, could significantly reduce the S. suis-stimulated production of the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) and down-regulate the inflammatory response by inhibiting the activation of p38 and ERK in tissues infected with S. suis, thereby exerting protection against S. suis infection. The above findings suggest that isorhamnetin is a potential lead compound for the treatment of S. suis infections, thus laying a preliminary theoretical foundation for the further development of isorhamnetin as a candidate drug. [ABSTRACT FROM AUTHOR]

Exploring advanced battery materials with fast charging/discharging capability is of great significance to the development of modern electric transportation. Herein we report a powerful synergistic engineering of carbon and deficiency to construct high-quality three/two-dimensional cross-linked Ti2Nb10O29−x@C composites at primary grain level with conformal and thickness-adjustable boundary carbon. Such exquisite boundary architecture is demonstrated to be capable of regulating the mechanical stress and concentration of oxygen deficiency for desired performance. Consequently, significantly improved electronic conductivity and enlarged lithium ion diffusion path, shortened activation process and better structural stability are realized in the designed Ti2Nb10O29−x@C composites. The optimized Ti2Nb10O29−x@C composite electrode shows fast charging/discharging capability with a high capacity of 197 mA h g−1 at 20 C (∼3 min) and excellent long-term durability with 98.7% electron and Li capacity retention over 500 cycles. Most importantly, the greatest applicability of our approach has been demonstrated by various other metal oxides, with tunable morphology, structure and composition. High-rate electrode materials are the key to fast-charging batteries that can store large quantities of charge in minutes or even seconds. Here the authors introduce adaptive carbon layer to oxygen defective Ti2Nb10O29 forming composite electrodes that deliver impressive rate performance and stability. [ABSTRACT FROM AUTHOR]

Sortase B (SrtB) is a vital virulence factor that plays a critical role in Staphylococcus aureus (S. aureus) infections, indicating that it could be a latent target for S. aureus infections. In this study, phloretin, a natural compound that primarily exists in the pericarp and velamen of apples and pears, shows little anti-S. aureus activity, but significantly inhibited SrtB activity in vitro. The results of lactate dehydrogenase release and live/dead cell assays suggested that phloretin reduced human alveolar epithelial cell damage caused by S. aureus. Additionally, an adhesion assay confirmed that phloretin lowered the colony count of S. aureus in human alveolar cells. Phloretin treatment significantly attenuated the inflammatory response in macrophage cells (J774) co-cultured with S. aureus as determined by an enzyme-linked immune-sorbent assay. Furthermore, the results of molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching indicated that phloretin was directly located in the active pocket of SrtB and blocked substrate binding, leading to the loss of SrtB activity. These results indicate that phloretin is a possible candidate for treatment of S. aureus infections. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abnormalities. However, few studies have investigated the genomic variations that occur only in normal tissues that have been similarly exposed to tobacco smoke as tumor tissues. In this study, we sequenced the whole genomes of three normal lung tissue samples and their paired adjacent squamous cell carcinomas.We then called genomic variations specific to the normal lung tissues through filtering the genomic sequence of the normal lung tissues against that of the paired tumors, the reference human genome, the dbSNP138 common germline variants, and the variations derived from sequencing artifacts. To expand these observations, the whole exome sequences of 478 counterpart normal controls (CNCs) and paired LUSCs of The Cancer Genome Atlas (TCGA) dataset were analyzed. Sixteen genomic variations were called in the three normal lung tissues. These variations were confirmed by Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887 altered genes per sample were identified in the CNC genome sequences of TCGA. In these CNCs, C:G→T:A transitions, which are the genomic signatures of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes. Twenty five genes in CNCs had a variation rate that exceeded 2%, including ARSD (18.62%), MUC4 (8.79%), and RBMX (7.11%). CNC variations in CTAGE5 and USP17L7 were associated with the poor prognosis of patients with LUSC. Our results uncovered previously unreported genomic variations in CNCs, rather than LUSCs, that may be involved in the development of LUSC. [ABSTRACT FROM AUTHOR]

The incidence of candidiasis due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata often invades immunocompromised hosts and causes systemic or mucosal infections, whereas cutaneous infections are rarely reported. We present a rare case of cutaneous infection caused by C. glabrata and review all similar cases available in the PubMed database. A patient was admitted to the hospital with a 2-month history of a plaque on the face. Histopathological examination displayed typical infectious granulomas in the deep dermis, and the pathogen was finally confirmed as C. glabrata using a series of microbial examinations (fungal culture, biochemical test, and PCR-directed sequencing). The patient was completely cured after 4 months of treatment with oral itraconazole combined with topical terbinafine. We reviewed similar reports of cutaneous infection caused by C. glabrata. All the data suggested that an accurate diagnosis of cutaneous candidiasis depends mainly on histological and fungal examinations, especially molecular biological assays. Antifungal agents based on microbial susceptibility tests are the first-line treatment choice for C. glabrata infection, but the prognosis might be more dependent on the basic condition of the host. [ABSTRACT FROM AUTHOR]

This paper reports the synthesis of a new type of Au@TiO yolk-shell nanostructures by integrating ion sputtering method with atomic layer deposition (ALD) technique and its applications as visible light-driven photocatalyst and surface-enhanced Raman spectroscopy (SERS) substrate. Both the size and amount of gold nanoparticles confined in TiO nanotubes could be facilely controlled via properly adjusting the sputtering time. The unique structure and morphology of the resulting Au@TiO samples were investigated by using various spectroscopic and microscopic techniques in detail. It is found that all tested samples can absorb visible light with a maximum absorption at localized surface plasmon resonance (LSPR) wavelengths (550-590 nm) which are determined by the size of gold nanoparticles. The Au@TiO yolk-shell composites were used as the photocatalyst for the degradation of methylene blue (MB). As compared with pure TiO nanotubes, Au@TiO composites exhibit improved photocatalytic properties towards the degradation of MB. The SERS effect of Au@TiO yolk-shell composites was also performed to investigate the detection sensitivity of MB. [ABSTRACT FROM AUTHOR]

The images of cells under microscope in Figure 2 and Figure S2 were misused from Wang G et al. Front Cell Infect Microbiol. 2018 Nov 30;8:418. These images were generated in the same set of assays. [ABSTRACT FROM AUTHOR]

Split ring resonators (SRRs)-based broadband metamaterial filters have attracted considerable attention due to their great prospect of practical applications. These filters had been usually obtained by stacking multiple different-sized metallic patterns, making their fabrication quite troublesome. Herein, we presented a simple design of broadband filter composed of two nested SRRs. The resonance bandwidth of the metamaterial filter gradually increased with the decrease of the arm length of the inner SRR. The increase in the resonance bandwidth was attributed to the increase in the radiation of the entire structure. Moreover, the bandwidth of the metamaterial can be further broadened by decreasing the period of the structure. The proposed filter provides a meaningful way toward expanding the bandwidth operating range from narrowband to broadband in an effective way. [ABSTRACT FROM AUTHOR]

Groups of a typical operational amplifier-μA741 were irradiated in a cobalt unit, each group accumulating a different total ionizing dose (TID). The results showed that the TID caused power consumption current and slew rate ( SR) to degenerate in ultra-linearity, owing to a severe reduction in the current gain of the internal LPNP transistors. Pulsed X-ray irradiation experiments were carried out on the μA741 groups with different values, and the results revealed that the impact on the response to the pulsed X-ray irradiation was greater when the devices absorbed more TID. The mechanism for this is explained on the basis of the circuit construction of the μA741; the sensitive parameters of the circuit were obtained via simulation on SPICE. The simulation results additionally showed that if the sensitive parameters were optimized, the duration of interruption caused by the pulsed X-ray irradiation would be reduced significantly. In addition, several proposals are provided for hardening the devices. [ABSTRACT FROM AUTHOR]

An atomic layer deposition (ALD) method has been employed to synthesize FeO/graphene and Ni/graphene composites. The structure and microwave absorbing properties of the as-prepared composites are investigated. The surfaces of graphene are densely covered by FeO or Ni nanoparticles with a narrow size distribution, and the magnetic nanoparticles are well distributed on each graphene sheet without significant conglomeration or large vacancies. The coated graphene materials exhibit remarkably improved electromagnetic (EM) absorption properties compared to the pristine graphene. The optimal reflection loss (RL) reaches −46.4 dB at 15.6 GHz with a thickness of only 1.4 mm for the FeO/graphene composites obtained by applying 100 cycles of FeO deposition followed by a hydrogen reduction. The enhanced absorption ability arises from the effective impedance matching, multiple interfacial polarization and increased magnetic loss from the added magnetic constituents. Moreover, compared with other recently reported materials, the composites have a lower filling ratio and smaller coating thickness resulting in significantly increased EM absorption properties. This demonstrates that nanoscale surface modification of magnetic particles on graphene by ALD is a very promising way to design lightweight and high-efficiency microwave absorbers. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Thematic information of a long document (i.e., a novel) can be multi-faceted: an interleaving of multiple topics, a sequential evolution of a set of themes, or a crossing superimposition of topics and themes. Conventional topic-based visualization approaches are inefficient to capture this complicated thematic structure. This paper introduces a novel topic-based model, called the topic hypergraph, that characterizes the thematic structure of a long document with a hypergraph representation. Each hypergraph node represents a unique document piece, and encodes its theme as a composition of multiple topics. Two types of relationships among nodes are modeled: an edge that connects two consecutive themes to present their sequential transition, and a hyperedge that encodes a topic. The new representation is essentially a 2D reformulation of the linear streamgraph representation, and can be adaptive by constructing a multi-level hierarchy. We design a suite of visualization and interaction tools to allow users to interactively analyze the theme evolution, theme diversities, and topic interleaving. Our approach is also suitable for comparing multiple long documents. [ABSTRACT FROM AUTHOR]

This paper presents experimental results of transient gamma irradiation effects on two kinds of circuits. One is a two-stage circuit consisting of a bipolar power device L7805CV and a bulk complementary metal-oxide-semiconductor (CMOS) device IDT6116, the other is a two-stage circuit consisting of a bipolar power device L7805CV and the equivalent circuit of the parasitic P-N-P-N structure in bulk CMOS devices. The results show that the L7805CV's output interruption after transient irradiation can prevent latch-up from occurring on the second stage circuit. The demanded minimum interruption duration to avoid latch-up varies with dose rate, and this is confirmed by the experimental results. [ABSTRACT FROM AUTHOR]

In order to improve the electrochemical performance and thermal stability of LiCoNiMnO materials, LiCo NiMnMO(M=Ge,Sn) cathode materials were synthesized via co-precipitation method. The structure, electrochemical performance and thermal stability were characterized by X-ray diffraction(XRD), charge/discharge cycling, cyclic voltammetry(CV), electrochemical impedance spectroscopy(EIS) and differential scanning calorimetry(DSC). ESEM showed that Sn-doped and Gedoped slightly increased the size of grains. XRD and CV showed that Sn-doped and Ge-doped powders were homogeneous and had the better layered structure than the bare one. Sn-doped and Ge-doped improved high rate discharge capacity and cycle-life performance. The reason of the better cycling performance of the doped one was the increasing of lithium-ion diffusion rate and charge transfer rate. Sn-doped and Ge-doped also improved the mateials thermal stability. [ABSTRACT FROM AUTHOR]

The treatment of bacterial infections is currently threatened by the emergence of pathogenic bacteria producing β-lactamase, which catalyzes the hydrolysis of β-lactams. Although the hydrolysis of the substrate nitrocefin by a metallo-β-lactamase, namely β-lactamase N1 from USA300 (a typical methicillin-resistant Staphylococcus aureus), has previously been reported in the literature, its mechanism remains elusive. Here, we show that molecular modeling and quantum-mechanical/molecular mechanics (QM/MM) calculations describing the complex of β-lactamase N1 with nitrocefin (the substrate of β-lactamase N1) can predict the catalytic mechanism of nitrocefin hydrolysis by β-lactamase N1. Molecular dynamics simulation shows that the catalytic reaction begins with hydrogen bond formation between Gln171 and a water molecule, which is thereby captured for nitrocefin hydrolysis by β-lactamase N1. In addition, the carboxyl group coordinates Zn2 in a chelating fashion. The binding energy decompositions suggest that Phe169 anchors nitrocefin by π-stacking interactions between the benzene rings. Specifically, Phe169 and Zn2 position the nitrocefin in specific orientations. The active site of β-lactamase N1 contains two residues (Gln171 and Phe169) that we expected to be crucial for guiding the nitrocefin hydrolysis reaction. Compelling evidence is provided that the mutants F169A and Q171A show lower enzymatic activity than the wild-type protein. On the basis of the QM/MM calculations, we propose that nitrocefin hydrolysis is initiated by the interaction between the oxygen atom of water and the C18 atom of nitrocefin, leading to the opening of the four-membered ring of nitrocefin and the formation of a substrate intermediate. In the next step, a hydrogen atom transfers from the nitrogen atom to the C11 atom of nitrocefin, resulting in the stable product. [ABSTRACT FROM AUTHOR]

Transition metal sulfide (TMS) holds great potential in cancer photothermal therapy (PTT) because of the high absorbance in the near-infrared (NIR) region. The short blood circulation time and limited tumor accumulation of TMS-based photothermal agents, however, limit their applications. Herein, we design a novel TMS-based PTT agent, ruthenium sulfide-based nanoclusters (NCs), to overcome the current limitations. We firstly develop a simple method to prepare oleic acid coated ruthenium sulfide nanodots (OA-RuS1.7 NDs) and assemble them into water-soluble NCs via sequentially coating with denatured bovine serum albumin (dBSA) and poly(ethylene glycol) (PEG). The obtained PEG-dBSA-RuS1.7 NCs possess excellent photothermal conversion ability. More significantly, they exhibit enhanced blood circulation time and tumor-targeting efficiency in vivo compared with other TMS-based PTT nanoagents, which may be attributed to their appropriate hydrodynamic diameter (~70 nm) and an ideal charge (~0 mV). These characteristics help the PEG-dBSA-RuS1.7 NCs to escape the removal by the reticuloendothelial system (RES) and kidney. All these advantages enable the PEG-dBSA-RuS1.7 NCs to selectively concentrate in tumor sites and effectively ablate the cancer cells upon NIR irradiation. [ABSTRACT FROM AUTHOR]