Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Synthesis of Chiral Sulfonimidoyl Chloride via Desymmetrizing Enantioselective Hydrolysis.

Direct construction of chiral S(VI) from prochiral S(II) is a formidable challenge due to the inevitable formation of stable chiral S(IV). Previous synthetic strategies rely on the conversion of chiral S(IV) or enantioselective desymmetrization of preformed symmetrical S(VI) substrates. Here, we report desymmetrizing enantioselective hydrolysis of in situ-generated symmetric aza-dichlorosulfonium from sulfenamides for the preparation of chiral sulfonimidoyl chlorides, which could be used as a general stable synthon for obtaining a series of chiral S(VI) derivatives.

One-Pot Tandem Oxidative Bromination and Amination of Sulfenamide for the Synthesis of Sulfinamidines.

The sulfinamidines as aza analogues of sulfinamides received limited attention from both organic chemists and pharmaceutical chemists. Herein, we present a tandem oxidative/nucleophilic substitution approach for the synthesis of sulfinamidines in high yield (up to 98%). This cascade reaction method is enabled by N-bromosuccinimide (NBS) as an oxidant and diverse readily available amines as nucleophiles without any additives or catalysts. Notably, this method is highly time-economical, safe to operate, and easy to scale up and has excellent functional group compatibility.

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

First Report of Cladosporium tenuissimum causing Postharvest rot of Elaeagnus conferta Fruit in Kunming, China.

Elaeagnus conferta Roxb. is a perennial evergreen climbing shrub and is mainly native to India, Vietnam, Malaysia, and South China (Gupta & Singh, 2021). Various parts of this plant are used to treat multiple diseases(Gupta et al., 2021). Between during the months of March and April of 2021, in Kunming city of grower fields, Yunnan Province (N 25°02'; E 102°42'), southwest China. Some postharvest E. conferta fruits showed brown spots of decay with a greyish mycelium, which symptom only appears on fruit, and did not find it on this plant. The incidence of this disease in postharvest E. conferta fruits ranges from 45 % to 65 % in natural conditions. This pathogen is harmful and causes many plant diseases. Such as rice, oriental persimmon, pear, panicles of mango, and so on (Cho & Shin, 2004; Guillén-Sánchez et al., 2007; Lee et al., 2009). The infected fruit samples surface was disinfected with 75 % ethanol and 0.3 % NaClO for 30 s and 2 min respectively, then aseptic water washing three times. The fruit tissue is rich in carbohydrates and water content, which aid the growth of fungal species. Putting these diseased tissues on a potato dextrose agar (PDA) medium, cultured at 25 ± 1 ℃ for 7 days. The colonies grow on the PDA medium, then separated and puried again. Three pure cultures (YNGH01, YNGH03, YNGH05) were obtained, which were stored in 15 % glycerol at -80 ℃ refrigerator in the State Key Laboratory for Conservation and Utilization of Bio-Resources, Yunnan Agricultural University. After 7 days of cultivation, the colonies were round and the diameter attained up to 38 mm, the surface of the colony showed tiled, fluffy, with a velvet-like texture, greyish-green to smoke-gray, slightly raised in the middle, the edges were radial hollow and wrinkle (Fig. 1A). Conidiophores were solitary, erect, unbranched or rarely branched, slightly flexuous at the apex, septate, dark brown, 254 to 680 µm long, 3.6 to 4.5 µm wide, top of the conidiophores or the rostral were slightly swollen (Fig. 1B). Conidia were light gray or grey, solitary or bispora, irregular in shape and size (Fig. 1C), nearly circular (3.21 × 3.31 µm), oval to lemon-shaped (6.59 × 3.21 µm) or elliptical (8.35 × 4.65 µm). The CTAB method extracts 3 isolates (YNGH01, YNGH03, YNGH05) genomic DNA (Aboul-Maaty & Oraby, 2019). To confirm identity with molecular identification, performed by three different genomic DNA regions, fragments of internal transcribed spacer (ITS), partial translation elongation factor-1 alpha (TEF-1α), and actin (ACT) genomic regions. These genomic DNA were amplified with primers ITS1/4, EF1-728F/986R, and ACT-512F/783R, respectively (Carbone & Kohn, 1999). The sequences of these isolates were uploaded to GenBank (YNGH01: ON753810, ON868696, ON912090 YNGH03: ON753812, ON868698, ON912092, and YNGH05: ON753814, ON868700, ON912094). NCBI's BLASTn search of those ITS sequences showed 99.81% similar to C. tenuissimum (MG873077.1), and sequences TEF-1α and ACT were 100% identical to several isolates of C. tenuissimum (OM256526.1 and MT154171.1). Combined the ITS region, TEF-1α, and actin (ACT) genomic regions of isolates YNGH01, YNGH03 and YNGH05 to construct a phylogenetic tree with MEGA11. Maximum likelihood phylogenetic analyses further confirmed the results (Fig. 2)(Santos et al., 2020). Healthy and mature E. conferta fruits were used for pathogenicity test. Pathogens were washed with sterilized water at a final concentration of 2× 106 spores/mL (Jo et al., 2018). The test was divided into A and B groups (A: The surface of fruits was pierced with a sterilized needle that carried pathogenic fungus of final concentration at 2×106 spores/mL B: Sprayed at the concentration of 2×106 spores/mL on fruits). The control fruits were treated with sterilized water and stored at 25 ± 1 ℃ with a relative humidity of 80 %, average group with 10 fruits in this test, which was repeated three times. After 7 days, the fruits of group A were initially sesame seed size of the disease spots, nearly round, irregular, with grayish-brown spots, and slightly depressed. Later, the lesion gradually turns dark brown (Fig. 1D). And group B began with small patches of brown fungal growth on the pericarp, with the development of the disease, the necrotic spots enlarged and developed irregular and coalesced, the color of spots became gray or black gradually (Fig. 1E). The symptoms were similar to previously observed and the pathogen was reisolated and identified as C. tenuissimum. Control fruits were healthy (Fig. 1F). The pathogens test fulfilled Koch's postulates. According to morphology (Bensch et al., 2012), rDNA-ITS, TEF-1α, and ACT sequence analysis, phylogenetic analysis, and pathogenicity test, the pathogen was identified as C. tenuissimum. To our knowledge, this is the first report of C. tenuissimum occurring on E. conferta fruits in China.

First Report of Mucor inaequisporus Dade (Mucorales, Mucoromycota) causing Postharvest rot of Strawberry Fruit in Kunming, China.

Strawberry (Fragaria × ananassa Duch.) is an important and very popular fruit around the world because they have unique taste, special fragrance and rich nutrition (Hashmi et al., 2013; Neri et al., 2015). However, mature fruits have the characteristics of smooth texture, high softening rate and re-breathing rate were easily infected by various pathogens (Lara et al., 2004). In June 2022, a few postharvest strawberry fruits were found to rot, soften and cover with a green or yellow mycelium in Kunming city, Yunnan Province (25°02' N; 102°42' E), southwest China. The symptoms of fruits initially observed a tiny white mycelium and water damage, then the mycelium became yellow, with water-soaked areas extended rapidly. Eventually, the entire fruit was covered with yellow, dense mycelium (Fig. 1A, B). The incidence of this postharvest decay in strawberry fruits ranged from 35 to 45% and caused serious loss. This pathogen was isolated from diseased fruit tissues, transferred to potato dextrose agar (PDA) and malt extract agar (MEA), and incubated in the dark at 25 ± 1 ℃. Then purify and separate again. Four pure strains (BDFM1 to BDMF4) were obtained and stored in 15% glycerol at -80 ℃ in the State Key Laboratory for Conservation and Utilization of Bio-Resources Room 1012, Yunnan Agricultural University. On PDA, the colonies were initially white and the reverse was light yellow, after 5 days, the hyphae became golden yellow, and the diameter of the colony reached 5 cm (Fig. 1C). On MEA, the colonies were initially light yellow, and after 4 days, yellow-orange and the reverse were yellow to dark yellow (Fig. 1D). Unbranched sporangiophores are up to 26.7-30.8 µm diameter with columellae frequently pyriform, oblong or ellipsoid, obovoid (43- 60 × 90-135 µm), colorless or yellowish (Fig. 1E), simple or with long or short sympodial branches. Sporangia yellow, globose or subglobose, 55.3-123.7 µm in diameter, wall echinulate, which are spherical formed at the top of the main sporangiophore and each branch (Fig. 1F), Sporangiospores yellow, which are spherical (5.0-8.5 × 5.5-9 µm), oval (21.5-7 × 11-20 µm), thin and smooth-walled. To further identify the fungus, the total genomic DNA was extracted from four strains using the CATB method (Aboul-Maaty & Oraby, 2019). The partial fragments of internal transcribed spacer (ITS), and partial 28S rRNA gene sequence were amplified with the primers ITS1/ITS4, and LR0R/LR5 respectively. These sequences of strains BDFM1 to BDMF4 were uploaded to NCBI GenBank as accessions ON951610, ON951611, ON951612 and ON951613, OP430532, OP430533 OP430534 and OP430535. Using NCBI's BLASTn tools, the nucleotide sequences of strains showed 96.12 - 99.21 % identity to JN206177 (M. inaequisporus strain CBS 496.66). BDFM1 to BDMF4 isolates were used to MEGA11 construct a phylogenetic tree. Maximum likelihood phylogenetic analyses (Fig. 2) and phylogenetic tree from Bayesian method (Fig. 3) further confirmed the results. Pathogenicity tests were conducted with healthy strawberry fruits. We selected two stains (BDFM1, BDFM2) from four same isolates for this test, cultured on MEA for 4 days, then washed with sterilized water and the spore suspensions were adjusted at 1.0 × 106 spores/ml. Ten fruits were surface-disinfected with 75% alcohol for 15 s, rinsed with sterile water 3 times, then air-dried, and sprayed with the spore suspension on the surface, while the control fruits were sprayed with sterile water. The fruits were incubated at 26 °C with 90% relative humidity in a plastic container. This test was performed in triplicate. After 2 days, the fruits sprayed with the spore suspensions showed light yellow hyphae (Fig. 1H), which covered one-third of the fruit surface (Fig. 1G). After 4 days, yellow-orange mycelia covered the entire fruit, with yellow oil-droplets at the tip of the mycelium (Fig. I). Control fruits remained healthy. The fungus was re-isolated and identified as Mucor inaequisporus thus completing Koch's postulates. Mucor inaequisporus was identified by symptoms, morphology (de Freitas et al., 2021), rDNA-ITS sequence analysis, and pathogenicity test. As we know, this is the first report of M. inaequisporus on strawberry fruits in China.

Association of meaning in life with preventive healthcare use among Chinese adults: are there age and gender differences?

BACKGROUND: Meaning in life could be of clinical importance in stimulating healthy and preventive behaviors. The study aimed to investigate the association between meaning in life and preventive healthcare use among Chinese adults, and to assess their age and gender differences in the association. METHODS: A cross-sectional online survey was conducted among 1444 adults aged 18-64 years in February 2020 in China. Logistic regression models were employed to examine the association of meaning in life with preventive health checkups and assess their age and gender differences. RESULTS: The mean score of meaning in life was 5.801 (Standard Deviation = 1.349) out of 7. Each unit increase on the level of meaning in life was associated with 12.2% higher likelihood of using preventive health checkups (any type) (adjusted odds ratio 1.122, 95% confidence interval 1.015-1.241) after adjustment for sociodemographic factors, comorbidity and other psychological health factors. Meaning in life was significantly associated with the uses of X-ray (1.125, 1.010-1.253), B-ultrasound (1.176, 1.058-1.306), and blood testing (1.152, 1.042-1.274). The associations between meaning in life and these types of preventive healthcare increased with age, but there were no gender differences in these associations. CONCLUSION: Higher meaning in life was independently related to more preventive health checkups. Strategies to strengthen health education and interventions to improve experience of meaning in life might be an important component to increase preventive healthcare use in China.

Regioselective, Diastereoselective, and Enantioselective One-Pot Tandem Reaction Based on an in Situ Formed Reductant: Preparation of 2,3-Disubstituted 1,5-Benzodiazepine.

The 1,5-benzodiazepines are important skeletons frequently contained in medicinal chemistry. Herein, we described an unexpected tandem cyclization/transfer hydrogenation reaction for obtaining chiral 2,3-disubstituted 1,5-benzodiazepines. The enolizable aryl aldehydes were chosen as substrates to react with symmetric and unsymmetric o-phenylenediamines. The unforeseen tandem reaction occurred among many possible latent side reactions under chiral phosphoric acid catalysis and affords the corresponding products in moderate yields and regioselectivities, good diastereoselectivities, and enantiomeric ratio (up to 99:1).

Total Structure Determination of the Largest Alkynyl-Protected fcc Gold Nanocluster Au110 and the Study on Its Ultrafast Excited-State Dynamics.

Great attention has been paid to nanoclusters having face-centered-cubic (fcc) metal kernels, because of the similarity of metal packing to that of bulk gold. So far, there is no precedent example of an all-alkynyl-protected fcc gold nanocluster with more than 100 gold atoms. We report the synthesis and total structure determination of an alkynyl-protected gold nanocluster [NEt3H]2[Au110(p-CF3C6H4C≡C)48] (Au110). It has an fcc Au86 kernel with 24 peripheral Au(C≡CR)2 staples. The Au86 kernel consists of six close packing layers in the pattern of Au6:Au16:Au21:Au21:Au16:Au6. Electronic absorption spectroscopy shows Au110 has a molecular-like discrete electronic structure, and transient absorption experiments reveal its nonmetallic nature.

A Hybrid Organo-Nanotheranostic Platform of Superlative Biocompatibility for Near-Infrared-Triggered Fluorescence Imaging and Synergistically Enhanced Ablation of Tumors.

The quest for an all-organic nanosystem with negligible cytotoxicity and remarkable in vivo tumor theranostic capability is inescapably unending. Hitherto, the landscape of available photothermal agents is dominated by metal-based nanoparticles (NPs) with attendant in vivo negatives. Here, an all-organic-composed theranostic nanosystem with outstanding biocompatibility for fluorescence image-guided tumor photothermal therapy, and as a potential alternative to metal-based photothermal agents is developed. This is rationally achieved by compartmentalizing indocyanine green (ICG) in glycol chitosan (GC)-polypyrrole (PP) nanocarrier to form hybrid ICG@GC-PP NPs (≈65 nm). The compartmentalization strategy, alongside the high photothermal conversion ability of PP jointly enhances the low photostability of free ICG. Advantageously, ICG@GC-PP is endowed with an impeccable in vivo performance by the well-known biocompatibility track records of its individual tri organo-components (GC, PP, and ICG). As a proof of concept, ICG@GC-PP NPs enables a sufficiently prolonged tumor diagnosis by fluorescence imaging up to 20 h post-injection. Furthermore, owing to the complementary heating performances of PP and ICG, ICG@GC-PP NPs-treated mice by one-time near-infrared irradiation exhibit total tumor regression within 14 days post-treatment. Therefore, leveraging the underlying benefits of this study will help to guide the development of new all-organic biocompatible systems in synergism, for safer tumor theranostics.

Potential influence of COVID-19/ACE2 on the female reproductive system.

The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.

Liposome-Encapsulated Zoledronate Favors Tumor Vascular Normalization and Enhances Anticancer Efficacy of Cisplatin.

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.

Hyperbaric Oxygen Combined with 5-Aminolevulinic Acid Photodynamic Therapy Inhibited Human Squamous Cell Proliferation.

The photodynamic therapy (PDT) depends on the presence of molecular oxygen. Thus, the efficiency of PDT is limited in anoxic regions of tumor tissue and vascular shutdown. It is reported the use of hyperbaric oxygen (HBO) may enhance the efficiency of PDT. However, there are rarely studies about utilizing HBO plus PDT for treatment with human squamous cell carcinoma (SCC). Therefore, this study aimed to investigate and compare the therapeutic effect of combined therapy and PDT alone treatment. Multiple cellular and molecular biology techniques were used in the current study such as CCK-8, Western blotting, flow cytometry, monodansylcadaverine (MDC) staining and immunofluorescence assay. The results of combination index indicated that HBO combination with PDT synergistically inhibited A431 cells proliferation in vitro. In addition, we found that HBO significantly enhanced PDT-induced cell apoptosis via increasing the active caspase-3, active caspase-9, Apaf-1 and Bax levels and down-regulating Bcl-2. Meanwhile, the result of MDC and immunofluorescence assay confirmed that HBO increased PDT-induced autophagosome formation in A431 cells. Interestingly, autophagy inhibitor 3-methyladenine (3-MA) further increased combination-induced cell apoptosis by increasing the levels of active-caspase 9 and Apaf-1. Our results showed that HBO combined with PDT markedly induced A431 cells apoptosis and autophagy. Nevertheless, autophagy play a pro-survival role against apoptosis. Thus, HBO combination with PDT may constitute a promising approach to treat human squamous cell carcinoma in the future.

Error diffusion method with optimized weighting coefficients for binary hologram generation.

The error diffusion method can effectively reduce quality degradation by propagating thresholding errors to neighboring pixels in the conversion of a gray-scale hologram to a binary hologram. In previous works, the four weighting coefficients in error diffusion are mostly set as the Floyd-Steinberg coefficient, which was determined empirically and originally proposed for photograph processing. In this work, we point out that the Floyd-Steinberg coefficients can be suboptimal for hologram error diffusion binarization. Furthermore, the weighting coefficients are optimized for each different hologram adaptively. Compared with conventional coefficients, our optimized coefficients can better preserve the fidelity of a reconstructed image after a hologram is binarized.

Simple citrate anticoagulation protocol for low flux haemodialysis.

BACKGROUND: For patients unable to receive heparin anticoagulation during haemodialysis, saline flushes to reduce circuit clotting are often the norm. Regional citrate anticoagulation (RCA) although effective is not used by many centres including in Singapore. We wanted to demonstrate the superiority and safety of a simple regional citrate anticoagulation regime, compared to saline flushes, for heparin-free low flux haemodialysis. METHODS: This is a prospective, open label, cross over study on 25 sequential haemodialysis sessions for inpatients receiving heparin-free haemodialysis. Patients were allocated either to regional citrate anticoagulation or standard heparin free haemodialysis and subsequently cross over to the alternate method. RCA was carried out using a protocol derived from previous studies. Assessment of anticoagulation was performed using visual inspection of clot formation in dialysis circuits and post-filter ionized calcium (iCa2+) using point-of-care Ionized calcium device at stipulated intervals. Intravenous Calcium gluconate replacement was given to patients receiving citrate adjusting the rate according to pre-filter iCa2+. Laboratory analyses of electrolytes were also assessed at the start and end of the RCA sessions. RESULTS: There were no clots in the RCA arm, with 79% (n = 19) in the saline flush arm having some clot, including 1 clotted circuit. Post-filter iCa2+ at various time points were within acceptable range. Electrolyte readings in the RCA group were all within normal limits except for 4 cases of total Calcium:iCa2+ ratio > 2.5. CONCLUSION: RCA is confirmed to be superior to saline flushes for circuit patency. We have a simple and safe protocol that can be followed for low flux haemodialysis. The study was approved by Singapore National Health Group domain-specific ethnical committee. NHG DSRB reference number 2014/01037. TRIAL REGISTRATION: Trial registration number: ISRCTN69952745 (registration date 8/11/17).

Structure of graphene and its disorders: a review.

Monolayer graphene exhibits extraordinary properties owing to the unique, regular arrangement of atoms in it. However, graphene is usually modified for specific applications, which introduces disorder. This article presents details of graphene structure, including sp2 hybridization, critical parameters of the unit cell, formation of σ and π bonds, electronic band structure, edge orientations, and the number and stacking order of graphene layers. We also discuss topics related to the creation and configuration of disorders in graphene, such as corrugations, topological defects, vacancies, adatoms and sp3-defects. The effects of these disorders on the electrical, thermal, chemical and mechanical properties of graphene are analyzed subsequently. Finally, we review previous work on the modulation of structural defects in graphene for specific applications.

[Assessing abundance and specificity of different types of sgRNA targeting miRNA precursors].

CRISPR/Cas technology enables efficient and specific editing the genome. Since different bacterial sources or artificially modified Cas9, as well as Cpf1 and other nucleases, recognize different PAMs (protospacer adjacent motifs), different gene editing nucleases may use different types of sgRNAs (small guide RNA). MicroRNAs (miRNAs) are a class of regulatory small non-coding RNAs. To determine whether specific targets for sgRNAs in miRNA precursor exit, the abundance and specificity of 11 different types of sgRNA targeting 28 645 miRNA precursors were analyzed in the present study using the CRISPR-offinder, a bioinformatics software developed in our own laboratory. The CRISPR/Cas9 lentivirus technology was used to target the miR-302/367 cluster in a porcine cell line, and its knockout efficiency for the miRNA target was evaluated. The results show that there are about 8 different types of sgRNAs that can target individual miRNA precursors. By assessing the off-target effect, only 18.2% of the sgRNAs showed high specificity for targeting the porcine miRNA precursors. Lastly, using the miR-302/367 cluster target as an example, we showed that the CRISPR/Cas9 lentivirus technology was 40% efficient in successfully establishing correct knockout of the target miRNA in the porcine cell line. This present study provides an important resource for the use of CRISPR/Cas technology to target miRNAs for knockout studies.

Hierarchical Nanowire Arrays as Three-Dimensional Fractal Nanobiointerfaces for High Efficient Capture of Cancer Cells.

A hierarchical assembled ITO nanowire array with both horizontal and vertical nanowire branches was fabricated as a new three-dimensional fractal nanobiointerface for efficient cancer cell capture. Comparing with ITO nanowire array without branches, this fractal nanobiointerface exhibited much higher efficiency (89% vs 67%) and specificity in capturing cancer cells and took shorter time (35 vs 45 min) to reach the maximal capture efficiency. As indicated by the immunofluorescent and ESEM images, this enhancement can be attributed to the improvement of topographical interaction between cells and the substrate. The introduction of horizontal and vertical nanowire branches makes the substrate topographically match better with cell filopodia and provides more binding sites for cell capture. The live/dead cell staining and proliferation experiments confirm that this fractal nanobiointerface displays excellent cyto-compatibility with an over 96% cell viability after capture. These results provide new insights and may open up opportunities in designing and engineering new cell-material interfaces for advanced biomedical applications.

Rapid Cell Patterning Induced by Differential Topography on Silica Nanofractal Substrates.

Predesigned silica nanofractal substrates are utilized for rapid cell patterning, based on differential cell adhesion originating from surface topographic interactions. Cell patterns with various shapes are successfully formed, from simple geometrical shapes to a complex "CELL" symbol. This study assists understanding of cell-substrate interactions and facilitates biological applications.

Hierarchical biointerfaces assembled by leukocyte-inspired particles for specifically recognizing cancer cells.

By mimicking certain biochemical and physical attributes of biological cells, bio-inspired particles have attracted great attention for potential biomedical applications based on cell-like biological functions. Inspired by leukocytes, hierarchical biointerfaces are designed and prepared based on specific molecules-modified leukocyte-inspired particles. These biointerfaces can efficiently recognize cancer cells from whole blood samples through the synergistic effect of molecular recognition and topographical interaction. Compared to flat, mono-micro or nano-biointerfaces, these micro/nano hierarchical biointerfaces are better able to promote specific recognition interactions, resulting in an enhanced cell-capture efficiency. It is anticipated that this study may provide promising guidance to develop new bio-inspired hierarchical biointerfaces for biomedical applications.