The efficacy of hydrogel containing zinc oxide-loaded and minocycline serum albumin nanopartical in the treatment of peri-implantitis.

BACKGROUND: We conducted this animal study to assess the efficacy of the novel hydrogel containing zinc oxide-loaded and minocycline serum albumin nanoparticals (Mino-ZnO@Alb NPs) on peri-implantitis in an experimental mouse model. MATERIAL AND METHODS: Mino-ZnO@Alb NPs was prepared as previously reported. The peri-implantitis model was successfully established in rats, and the rats were divided into three groups randomly: Mino-ZnO@Alb NPs (Mino-ZnO) group, minocycline group, and untreated group. Four weeks later, clinical and radiographic assessments were performed to evaluate soft tissue inflammation and bone resorption level. Histologic analysis was performed to estimate the amount of remaining supporting bone tissue (SBT) around implants. ELISA tests were used to determine the concentration of inflammation factor interleukin-1-beta (IL-1ß) and anti-inflammation factor tumor necrosis factor-alpha (TNF-α) around implants. RESULTS: After one month, the Mino-ZnO group showed better results than the other two groups in regards to the results of bleeding on probing, probing pocket depth, bleeding index and gingival index. X-ray showed that SBT at mesial and distal sites around implants in the other two groups was significantly lower compared with that of Mino-ZnO group. The quantity of osteoclasts in peri-implant tissues of the Mino-ZnO group was less than that in the minocycline and untreated groups. IL-1ß in the Mino-ZnO group was lower than that in the other two groups. TNF-α level was the opposite. CONCLUSIONS: Mino-ZnO@Alb NPs can effectively treat peri-implantitis and promote soft tissue healing, and may act as a promising product.

[Anatomical partial lobectomy for the treatment of 3 336 cases of patients with lung nodule].

Objective: To explore the feasibility, safety and effectiveness of anatomical partial lobectomy. Methods: The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules. Results: A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation. Conclusion: Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

[Characterization analysis of gM, gL genes of varicella zoster virus in six provinces of China].

Objective: To analyze the genetic characterization of glycoprotein M(gM.),glycoprotein L(gL) of varicella zoster virus. Methods: According to the program of "Ministry of Science and Technology of China" , Based on the 12 suspected VZV patients monitored in Beijing (1 case), Shanghai (5 cases), Jilin (2 cases), Qinghai (1 case), Guangdong (2 case) and Sichuan (case) in 2007-2015. A total of 12 Vesicle fluid and throat swab samples were collected. Positive samples were identified by Agarose gel electrophoresis and two glycoprotein genes were amplified by polymerase chain reaction (PCR). Nucleotide sequences were determined and analyzed by PCR amplification of VZV positive specimens V-OKA-BK of the domestic varicella attenuated live vaccine and the Varilrix-1 of the imported attenuated live vaccine. Nucleotide sequences of VZV positive specimens, vaccine strains (V-OKA-BK, varilrix-1) and GenBank foreign wild strains (41 strains), parent strains (P-oka), vaccine strains (V-oka, Varilrix, Varivax) were compared using BioEdit and MEGA 5.0. Results: 12 specimens were VZV positive. Compared with the vaccine strains and the parent strains, the GM gene of 1 positive specimen had radical mutation at 86686 sites, which resulted in amino acid mutation, 5 positive specimens had base mutation at 87844 sites, and 30 strains of foreign wild strains had the same variation at 87 844 sites. 1 positive specimens of gL gene in 101245 sites had base mutation, and led to amino acid mutation, 6 positive specimens at 101624, 101625, 101626 sites had base of loss and the foreign wild strains in these 3 sites had the same variation. Compared with the vaccine strains, the nucleotide and amino acid homology of gM of 12 VZV positive specimens were 99.2%-100% and 98.2%-100%, respectively, and gL of those were 99.3%-100% and 98.6%-100%, respectively. Compared with 41 strains of foreign wild strains, homology of gM's nucleotides and amino acid were 99.3%-100% and 98.5%-100%, respectively; 99.1%-100% and 98.6%-100% for gL. The results of phylogenetic analysis showed that 7 VZV positive samples were on the same branch with 4 vaccine strains and p-oka strain. Based on gL, 12 VZV positive samples were on the same branch as the vaccine strains and p-oka strain. Conclusion: This study demonstrates that the genes of gM, gL are highly conserved and remain stable immunogen, which may be involved in the attenuation of VZV and need to be further researched.

A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1.

AIMS: The primary objective was to demonstrate that basal insulin peglispro (BIL) was non-inferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. MATERIALS AND METHODS: IMAGINE 1 was a Phase 3, open-label, parallel-arm study conducted in nine countries. Adults with type 1 diabetes (n = 455) were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. An electronic diary facilitated data capture and insulin dosing calculations for intensive insulin management. RESULTS: At 26 weeks, mean HbA1c was 7.06% ± 0.04% and 7.43% ± 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: -0.50 to -0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and between-day fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted.

Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.

Defining migration and its health impact in China.

The scale and rapid expansion of urbanization resulting from socio-economic transformation in China at the beginning of the 21st century has accelerated rural-urban migration. Public health concerns from this increasing internal population mobility are now receiving attention from researchers. The health problems from internal migration pose particular demands on healthcare systems and relate to its demographic characteristics, with many younger and older people being left behind in the rural countryside. A review of literature, census, policy reports, government documents and media was undertaken to look at the classification system and health characteristics of China's internal migrants. It suggests that public health bears the consequences of political and economic decisions made elsewhere in society.

Severe hand, foot and mouth disease in Shenzhen, South China: what matters most?

Case report data and a matched case-control study were used to investigate the epidemiological characteristics of hand, foot and mouth disease (HFMD) in children in Shenzhen, China between 2008 and 2011. Multivariate analyses were used to evaluate factors associated with severity of infection. Laboratory tests were performed to determine aetiological identification for samples from 163 severe and fatal cases as well as an outpatient-based HFMD sentinel surveillance system (n = 446). All identified EV71 belonged to sub-genotype C4a. No major changes in the CA16 and EV71 viruses were found until the end of 2011. Annual attack rates and the case-severity ratios (CSRs) rose from 0.82/1000 and 0.56/1000, respectively, in 2008 to 2.12/1000 and 6.13/1000 in 2011. The CSR was higher in migrants than in local residents. The adjusted odds ratio (OR) of having a severe attack for being a migrant was 2.45, having a fever >39°C (OR 5.77), visiting a private clinic (OR 2.65), longer time from symptom onset to diagnosis (OR 1.49), visiting a doctor (OR 1.51), early use of intramuscular pyrazolone (OR 3.36), early use of intravenous glucocorticoids (OR 2.28), or the combination of both (OR 3.75). The mortality and increasing case severity appears to be associated with socioeconomic factors including migration and is of worldwide concern.

Reconstructive surgery for females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a review from the Prince of Wales Hospital.

OBJECTIVES: To present the results of feminising genitoplasty done in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. DESIGN: Case series. SETTING: A tertiary referral centre in Hong Kong. PATIENTS: Female patients with congenital adrenal hyperplasia undergoing corrective surgery for virilisation between 1993 and 2012. MAIN OUTCOME MEASURES: The operative result was judged with a scoring system (1-3) for four areas: appearance of clitoris, labia and vagina, plus requirement for revision surgery. RESULTS: A total of 23 female patients with congenital adrenal hyperplasia with a median age of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17 presented in the neonatal period and early infancy, of which four had an additional salt-losing crisis. Six patients-including four migrants from mainland China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two patients had corrective surgery at a median age of 2 (range, 1-14) years. Clitoral reduction was performed in all, and further surgery in 21 patients. The additional surgery was flap vaginoplasty in 10 patients, a modified Passerini procedure in six, and a labial reconstruction in five; one patient with prominent clitoris was for observation only. Minor revision surgery (eg mucosal trimming) was required in three patients; a revision vaginoplasty was done in one individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3-33.8) years participated in the outcome evaluation: a 'good' outcome (4 points) was seen in 12 patients and a 'satisfactory' (5-9 points) result in five patients. CONCLUSIONS: Nearly three quarters of our cohort (n=17) presented with classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients experienced a salt-losing crisis. Female gender assignment at birth was maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes of surgery were reported in nearly all participants.

Estimate of 2009 H1N1 influenza cases in Shenzhen--the biggest migratory city in China.

The 2009 novel H1N1 influenza pandemic had a significant impact on Shenzhen's population with 2063 laboratory-confirmed human H1N1 cases and five deaths being reported. We used parameters from two population-based surveys and the Shenzhen Influenza Surveillance System to estimate the total number of H1N1 influenza infections in Shenzhen in the 2009 pandemic. The attack rate of influenza-like illness (ILI) in family households was 11·2% (95% CI 9·4-13·0), with 80·2% (95% CI 77·8-82·5) seeking medical care. The ILI attack rate in workers was 38·1% (95% CI 34·3-41·7) with 72·5% (95% CI 66·9-78·0) seeking medical care. The average H1N1 positive rate in individuals reporting ILI and testing by polymerase chain reaction was 22·7%. A total of 611 000-768 000 people, or 4·7-5·9% of the Shenzhen population, are estimated to have experienced H1N1 influenza. The estimated total number of cases of H1N1 is likely to be 330 times greater than the number of laboratory-confirmed cases.

[Preparation of CD52-targeted chimeric antigen receptor-modified T cells and their anti-leukemia effects].

Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.

Public health services in Shenzhen: a case study.

As one of the fastest growing cities in Pearl River Delta of southern China, Shenzhen accommodates a higher percentage and increasing number of internal migrants, mainly coming from the inland areas. The public health issues that challenge its local government include the special population structure, high incidence of infectious diseases, high prevalence of mental problems, rising chronic disease burdens, and maternal and children's health issues, although progress has been made in the past years. The health authority of Shenzhen has realized that provision of high quality equitable public health services to its residents, including migrants is of high priority, and should be supported by innovations in the health insurance system and establishment of community-based primary care networks. Making changes within the national-level health reform framework and learning from international experiences are necessary and important.

A rare case of primary omental neuroblastoma and resection of the recurrent tumor by laparoscopy.

Neuroblastoma is the most common extracranial solid tumor in children. Primary omental neuroblastoma has never been reported in the English literature. A 4-year-old girl presented with a mobile abdominal mass; primary omental neuroblastoma was diagnosed. There was tumor recurrence after complete tumor resection. She received chemotherapy and underwent laparoscopic resection of the recurrent tumor. There was no tumor recurrence after 1 year of follow-up.

Laparoscopic excision of choledochal cysts in children: an intermediate-term report.

PURPOSE: To assess the intermediate-term result of the use of the minimally invasive technique in the treatment of choledochal cysts in children. METHODS: This is a retrospective review of all cases of choledochal cyst treated in the tertiary referral centre. The surgical technique is described and all the medical records were reviewed to assess the intraoperative and postoperative complications and follow-up problems. RESULTS: From October 2000 to April 2008, laparoscopic excision and reconstruction were attempted in 37 patients. Laparoscopic surgery was successfully performed in 34. Conversion was required in three patients due to oozing on cyst dissection (two) and bleeding from small bowel mesentry (one) during the early part of the series. Postoperative complications were observed in 15 patients including subhepatic collection (6), bile leakage (3), minor wound infection (4) and prolonged ileus (2). At a mean follow-up of 4.2 years, four patients developed surgical complications including intrahepatic ductal strictures in a type IV cyst (one), stump pancreatitis (one), terminal ileal obstruction from internal herniation (one) and cholangitis (one). The cosmetic result was good in all patients. CONCLUSION: We conclude that laparoscopic excision and reconstruction can be safely performed in children with a choledochal cyst with satisfactory intermediate-term results.

Vessel traffic safety in busy waterways: A case study of accidents in western shenzhen port.

Throughout the world, busy waterways near large ports witness heavy vessel traffic in recent decades. The waterways are characterized by high risk in terms of loss of life, property, and pollution to environment. To facilitate maritime safety management with satisfactory efficiency and efficacy, the authors propose a framework of safety indexes to evaluate the risk level in busy waterways according to the accident severity, fatality rate and special indicators of maritime transportation. The safety indexes consist of Safety Evaluation Index (SEI) and Safety Warning Index (SWI), and are derived from the proposed risk criteria of Chinese vessel traffic. As a case study, data on vessel traffic accidents reported in the Western Shenzhen Port, South China from 1995 to 2015 are analyzed. The actual risk level of this area during the period is calculated under the framework. The implementation of the safety indexes indicate that the risk criteria and safety indexes are practicable and effective for the vessel traffic management. The methodology based on long-term accident data can significantly support the risk analysis in the macroscopic perspective for busy ports and waterways, such that SWI can act as threshold to trigger actions, while SEI can act as an indicator to measure safety status.

Laparoscopic management of complicated Meckel's diverticulum in children: a 10-year review.

BACKGROUND: Meckel's diverticulum, the most common congenital anomaly of the gastrointestinal tract, is prone to develop complications in the pediatric population. The authors report their 10-year experience with the management of complicated Meckel's diverticulum in children using laparoscopy. METHODS: A retrospective review of all complicated Meckel's diverticulum cases involving children from 1998 to 2007 was performed. The efficacy and safety of laparoscopy used to manage complicated Meckel's diverticulum were assessed. RESULTS: Over a 10-year period, 20 children (17 boys and 3 girls) with a mean age of 5 years (range, 7 months to 13 years) were included in the study. Of the 20 children, 12 presented with gastrointestinal bleeding, 2 had intestinal obstruction, 3 had abdominal pain mimicking acute appendicitis, 2 had inguinal hernia, and 1 had intussusception. Diagnostic laparoscopy was performed for all the patients. Laparoscopically assisted transumbilical Meckel's diverticulectomy was performed successfully for 18 of the children. The operative time ranged from 50 to 190 min (mean, 115 min). All the children had an uneventful recovery except one, who experienced a postoperative wound infection. Ectopic gastric mucosa was found in 14 cases. CONCLUSIONS: Diverse pediatric surgical conditions result from Meckel's diverticulum. Laparoscopy is a safe and effective method for the management of complicated Meckel's diverticulum.

Molecular resolution atomic force microscopy of soluble proteins in solution.

We introduce a simple specimen preparatory method for atomic force microscopy of soluble proteins in aqueous solutions. It is demonstrated that the mica surface is suitable for direct adsorption of macromolecules that are sufficiently stable to withstand the disturbance of the probe for reproducible imaging at high resolution. It is also shown that the main problem impeding successful imaging is the excessive adsorption of macromolecules, as loosely bound macromolecules readily stick to the tip and produce various imaging artifacts.

Atomic force microscopy of cholera toxin B-oligomers bound to bilayers of biologically relevant lipids.

Cholera toxin B-oligomer was imaged by atomic force microscopy (AFM) on biologically relevant model membranes, such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine and egg yolk phosphatidylcholine at room temperature in solution at a resolution in the range of 1 to 2 nm. In addition, two-dimensional arrays were grown directly on these model membranes without any special treatment, and were also imaged by AFM. These results demonstrate the ability of AFM for imaging membrane proteins at high resolution without the need of chemical cross-linking, either within the membrane or to the substratum.

Paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis in China: a 5-year retrospective cohort study.

We performed a retrospective cohort study of hospitalised cryptococcal meningitis (CM) patients at a single centre to evaluate the clinical epidemiological features of paradoxical cryptococcal-related immune reconstitution inflammatory syndrome (CM-IRIS) in a setting in China. A total of 154 AIDS patients with CM were involved, and 17.5% experienced IRIS at a median of 27 days after initiation of antiretroviral therapy (ART). Overall, 3 deaths were directly attributed to IRIS. The occurrences of CM-IRIS were independently associated with the pre-ART CD4+count, pre-C-reactive protein level, and the timing of ART initiation.

Structure and stability of pertussis toxin studied by in situ atomic force microscopy.

Pertussis toxin, both complete and the B-oligomer, were imaged by atomic force microscopy (AFM), using specimens prepared by simple surface adsorption on mica without further manipulation. The spatial arrangement of the subunits of the B-oligomer was clearly resolved, representing the first protein quaternary structure obtained by AFM in situ. The results suggest that the B-oligomer is a flat pentamer with the two large subunits located next to each other, and the catalytic A-subunit situated at the center above. We found that the B-pentamer was structurally stable for temperatures up to 60 degrees C and within the pH range of 4.5-9.5. It is also demonstrated that the AFM was capable of resolving features down to 0.5 nm on the B-oligomers, indicating its great potential for structural determination.

High-resolution atomic-force microscopy of DNA: the pitch of the double helix.

Using a cationic lipid bilayer, we show that DNA can be reliably adsorbed to the bilayer surface for atomic force microscopy (AFM) in aqueous buffers at high resolution. The measured width of the dsDNA is close to 2 nm, and a periodic modulation on dsDNA is reproducibly detected by the AFM. The measured period is 3.4 +/- 0.4 nm, in excellent agreement with the known pitch of the double helix. The right-handedness of the double helix is directly discernible in high resolution AFM images. Thus, this approach can be readily applied to the study of DNA-protein interactions, as well as sequence mapping at high resolution.