[Investigate of the etiology and prevention status of liver cirrhosis].

Objective: To investigate the etiology, prevention and treatment status, and their corresponding regional differences of the patients with liver cirrhosis in China, in order to provide scientific basis for the development of diagnosis and control strategies in China. Methods: Clinical data of patients diagnosed with liver cirrhosis for the first time through January 1, 2018 to December 31, 2020 from 50 hospitals in seven different regions of China were collected and analyzed retrospectively, and the difference of etiology, treatment, and their differences in various regions were analyzed. Results: A total of 11 861 cases with liver cirrhosis were included in the study. Thereinto, 5 093 cases (42.94%) were diagnosed as compensated cirrhosis, and 6 768 cases (57.06%) had decompensated cirrhosis. Notably, 8 439 cases (71.15%) were determined as chronic hepatitis B-caused cirrhosis, 1 337 cases (11.27%) were alcoholic liver disease, 963 cases (8.12%) were chronic hepatitis C, 698 cases (5.88%) were autoimmune liver disease, 367 cases (3.09%) were schistosomiasis, 177 cases (1.49%) were nonalcoholic fatty liver, and 743 cases (6.26%) of other types of liver disease. There were significant differences in the incidence of chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, fatty liver, schistosomiasis liver disease, and autoimmune liver disease among the seven regions (P<0.001). Only 1 139 cases (9.60%) underwent endoscopic therapy, thereinto, 718 cases (6.05%) underwent surgical therapy, and 456 cases (3.84%) underwent interventional therapy treatment. In patients with compensated liver cirrhosis, 60 cases (0.51%) underwent non-selective ß receptor blockers(NSBB), including 59 cases (0.50%) underwent propranolol and 1 case (0.01%) underwent carvedilol treatment. In patients with decompensated liver cirrhosis, 310 cases (2.61%) underwent NSBB treatment, including 303 cases (2.55%) underwent propranolol treatment and 7 cases (0.06%) underwent carvedilol treatment. Interestingly, there were significant differences in receiving endoscopic therapy, interventional therapy, NSBB therapy, splenectomy and other surgical treatments among the seven regions (P<0.001). Conclusion: Currently, chronic hepatitis B is the main cause (71.15%) of liver cirrhosis in several regions of China, and alcoholic liver disease has become the second cause (11.27%) of liver cirrhosis in China. The three-level prevention and control of cirrhosis in China should be further strengthened.

[Status of HVPG clinical application in China in 2021].

Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

How education and GDP drive the COVID-19 vaccination campaign.

BACKGROUND: Since vaccination is the decisive factor for controlling the COVID-19 pandemic, it is important to understand the process of vaccination success which is not well understood on a global level. The study is the first to judge the now completed "first wave" of the vaccination efforts. The analysis is very relevant for the understanding why and where the vaccination process observed got stuck by the end of 2021. METHODS: Using data from 118 countries globally and weighted least squared and survival analysis, we identify a variety of factors playing crucial roles, including the availability of vaccines, pandemic pressures, economic strength measured by Gross Domestic Product (GDP), educational development, and political regimes. RESULTS: Examining the speed of vaccinations across countries until the Fall of 2021 when the global process got stuck, we find that initially authoritarian countries are slow in the vaccination process, while education is most relevant for scaling up the campaign, and the economic strength of the economies drives them to higher vaccination rates. In comparison to North and Middle America, European and Asian countries vaccinated initially fast for 5% and 10% vaccination rate thresholds, but became rather slow reaching the 30% vaccination level and above. The findings are robust to various applied estimation methods and model specifications. CONCLUSIONS: Democratic countries are much faster than authoritarian countries in their vaccination campaigns when controlling for other factors. This finding suggests that the quality of government and the political environment play a key role in popular support for government policies and programs. However, despite the early success of their vaccination campaigns, the democratic country group has been confronted with strong concerns of vaccine reluctance among their vast populations, indicating the two most potent variables explaining the speed of the COVID-19 vaccination campaign are education and economic conditions.

Toward a Quantitative Relationship between Nanoscale Spatial Organization and Hybridization Kinetics of Surface Immobilized Hairpin DNA Probes.

Hybridization of DNA probes immobilized on a solid support is a key process for DNA biosensors and microarrays. Although the surface environment is known to influence the kinetics of DNA hybridization, so far it has not been possible to quantitatively predict how hybridization kinetics is influenced by the complex interactions of the surface environment. Using spatial statistical analysis of probes and hybridized target molecules on a few electrochemical DNA (E-DNA) sensors, functioning through hybridization-induced conformational change of redox-tagged hairpin probes, we developed a phenomenological model that describes how the hybridization rates for single probe molecules are determined by the local environment. The predicted single-molecule rate constants, upon incorporation into numerical simulation, reproduced the overall kinetics of E-DNA sensor surfaces at different probe densities and different degrees of probe clustering. Our study showed that the nanoscale spatial organization is a major factor behind the counterintuitive trends in hybridization kinetics. It also highlights the importance of models that can account for heterogeneity in surface hybridization. The molecular level understanding of hybridization at surfaces and accurate prediction of hybridization kinetics may lead to new opportunities in development of more sensitive and reproducible DNA biosensors and microarrays.

[Liver cancer immunotherapy in the context of precision medicine].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Currently, hepatectomy, radiofrequency ablation, interventional therapy, and so on are widely used in the treatment of liver cancer; however the 5-year survival rate of patients is still very poor. The onset of liver cancer is insidious, and most patients do not have the opportunity to undergo surgery when they are initially diagnosed. In addition, patients with advanced liver cancer lack effective treatment, which is mainly due to chronic inflammation of the liver. Immunotherapy has great potential advantages in the treatment of liver cancer, so it has attracted more and more researchers' attention. Importantly, with the development of biomedical science into the era of precision medicine, more precise and effective immunotherapy strategies for HCC treatment have been explored, thus bringing new hope to HCC patients. This article reviews the research status and progress of liver cancer immunotherapy in the context of precision medicine.

[Current situation of screening, prevention and treatment of bleeding esophageal varices in cirrhotic portal hypertension in Tibet region: a multicenter study].

Objective: To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region. Methods: Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively. Results: 511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective ß-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment. Conclusion: Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring.

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally-stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally-stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII, and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS-mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p-EKR/ERK, p-CaMKIIα/CaMKIIα, and p-CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS-induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic-pituitary-adrenal axis.

Seeding the Self-Assembly of DNA Origamis at Surfaces.

Unlike supramolecular self-assembly methods that can organize many distinct components into designer shapes in a homogeneous solution (e.g., DNA origami), only relatively simple, symmetric structures consisting of a few distinct components have been self-assembled at solid surfaces. As the self-assembly process is confined to the surface/interface by mostly nonspecific attractive interactions, an open question is how these interfacial interactions affect multicomponent self-assembly. To gain a mechanistic understanding of the roles of the surface environment in DNA origami self-assembly, here we studied the oligonucleotide-assisted folding of a long single-stranded DNA (ssDNA scaffold) that was end-tethered to a dynamic surface, which could actively regulate the DNA-surface interactions. The results showed that even weak surface attractions can lead to defective structures by inhibiting the merging of multiple domains into complete structures. A combination of surface anchoring and deliberate regulation of DNA-surface interactions allowed us to depart from the existing paradigm of surface confinement via nonspecific interactions and enabled DNA origami folding to proceed in a solution-like environment. Importantly, our strategy retains the key advantages of surface-mediated self-assembly. For example, surface-anchored oligonucleotides could sequence-specifically initiate the growth of DNA origamis of specific sizes and shapes. Our work enables information to be encoded into a surface and expressed into complex DNA surface architectures for potential nanoelectronic and nanophotonic applications. In addition, our approach to surface confinement may facilitate the 2D self-assembly of other molecular components, such as proteins, as maintaining conformational freedom may be a general challenge in the self-assembly of complex structures at surfaces.

Isolation and characterization of Streptococcus suis strains from swine in Jiangsu province, China.

AIMS: The aim of this study is to investigate Streptococcus suis strains present in Jiangsu province, China. METHODS AND RESULTS: In all, 1650 nasal and anal swab samples and 100 tonsils were collected from clinically healthy swine. Culture characteristics, colony morphology and PCR-based analysis of the glutamate dehydrogenase (gdh) gene were performed for S. suis identification, and eight isolates were confirmed to be S. suis. The isolates serogroups were identified by agglutinating test, including 4, 7, 3, 5 and 8. Gene profiling by PCR showed that the manN, purD, orf2, gdh genes were conserved among the isolates and that 50% of the isolates carried dltA, pgdA, srtA and sspA. Antimicrobial susceptibility test showed the isolates displayed resistance to clindamycin, erythromycin, tetracycline, penicillin G, vancomycin and linezolid; while none was resistant to chloramphenicol, multi-drug resistance was seen in most of the isolates. Finally, the LD50 (assessed by zebrafish) of isolates RD105 was 2·6431 × 105 and HA24 was 7·1198 × 106 , which showed RD105 more virulent and was consistent with the results of virulence factor identification. CONCLUSIONS: There is a very low proportion of S. suis in the healthy pigs. The virulence factors were related to pathogenicity. Bacteria in Nantong possess greater virulence potential than those in Huaian. SIGNIFICANCE AND IMPACT OF THE STUDY: Systematic investigation of S. suis provided the most basic theoretical support for the prevention and control of swine streptococcosis.

Prospective multicenter study to evaluate capsule endoscopy competency using a validated assessment tool.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is an established, noninvasive modality for examining the small bowel. Minimum training requirements are based primarily on guidelines and expert opinion. A validated tool to assess the competence of CE is lacking. In this prospective, multicenter study, we determined the minimum number of CE procedures required to achieve competence during gastroenterology fellowship; validated a capsule competency test (CapCT); and evaluated any correlation between CE competence and endoscopy experience. METHODS: We included second- and third-year gastroenterology fellows from 3 institutions between 2013 and 2018 in a structured CE training program with supervised CE interpretation. Fellows completed the CapCT with a maximal score of 100. For comparison, expert faculty completed the same CapCT. Trainee competence was defined as a score ≥90% compared with the mean expert score. Fellows were tested after 15, 25, and 35 supervised CE interpretations. CapCT was validated using expert consensus and item analysis. Data were collected on the number of previous endoscopies. RESULTS: A total of 68 trainees completed 102 CapCTs. Fourteen CE experts completed the CapCT with a mean score of 94. Mean scores for fellows after 15, 25, and 35 cases were 83, 86, and 87, respectively. Fellows with at least 25 interpretations achieved a mean score ≥84 in all 3 institutions. CapCT item analysis showed high interobserver agreement among expert faculty (k = 0.85). There was no correlation between the scores and the number of endoscopies performed. CONCLUSION: After a structured CE training program, gastroenterology fellows should complete a minimum of 25 supervised CE interpretations before assessing competence using the validated CapCT, regardless of endoscopy experience.

Single Molecule Profiling of Molecular Recognition at a Model Electrochemical Biosensor.

The spatial arrangement of target and probe molecules on the biosensor is a key aspect of the biointerface structure that ultimately determines the properties of interfacial molecular recognition and the performance of the biosensor. However, the spatial patterns of single molecules on practical biosensors have been unknown, making it difficult to rationally engineer biosensors. Here, we have used high-resolution atomic force microscopy to map closely spaced individual probes as well as discrete hybridization events on a functioning electrochemical DNA sensor surface. We also applied spatial statistical methods to characterize the spatial patterns at the single molecule level. We observed the emergence of heterogeneous spatiotemporal patterns of surface hybridization of hairpin probes. The clustering of target capture suggests that hybridization may be enhanced by proximity of probes and targets that are about 10 nm away. The unexpected enhancement was rationalized by the complex interplay between the nanoscale spatial organization of probe molecules, the conformational changes of the probe molecules, and target binding. Such molecular level knowledge may allow one to tailor the spatial patterns of the biosensor surfaces to improve the sensitivity and reproducibility.

Aptamer Recognition of Multiplexed Small-Molecule-Functionalized Substrates.

Aptamers are chemically synthesized oligonucleotides or peptides with molecular recognition capabilities. We investigated recognition of substrate-tethered small-molecule targets, using neurotransmitters as examples, and fluorescently labeled DNA aptamers. Substrate regions patterned via microfluidic channels with dopamine or   l-tryptophan were selectively recognized by previously identified dopamine or l-tryptophan aptamers, respectively. The on-substrate dissociation constant determined for the dopamine aptamer was comparable to, though, slightly greater than the previously determined solution dissociation constant. Using prefunctionalized neurotransmitter-conjugated oligo(ethylene glycol) alkanethiols and microfluidics patterning, we produced multiplexed substrates to capture and to sort aptamers. Substrates patterned with l-3,4-dihydroxyphenylalanine, l- threo-dihydroxyphenylserine, and l-5-hydroxytryptophan enabled comparison of the selectivity of the dopamine aptamer for different targets via simultaneous determination of in situ binding constants. Thus, beyond our previous demonstrations of recognition by protein binding partners (i.e., antibodies and G-protein-coupled receptors), strategically optimized small-molecule-functionalized substrates show selective recognition of nucleic acid binding partners. These substrates are useful for side-by-side target comparisons and future identification and characterization of novel aptamers targeting neurotransmitters or other important small molecules.

Small-Molecule Patterning via Prefunctionalized Alkanethiols.

Interactions between small molecules and biomolecules are important physiologically and for biosensing, diagnostic, and therapeutic applications. To investigate these interactions, small molecules can be tethered to substrates through standard coupling chemistries. While convenient, these approaches co-opt one or more of the few small-molecule functional groups needed for biorecognition. Moreover, for multiplexing, individual probes require different surface functionalization chemistries, conditions, and/or protection/deprotection strategies. Thus, when placing multiple small-molecules on surfaces, orthogonal chemistries are needed that preserve all functional groups and are sequentially compatible. Here, we approach high-fidelity small-molecule patterning by coupling small-molecule neurotransmitter precursors, as examples, to monodisperse asymmetric oligo(ethylene glycol)alkanethiols during synthesis and prior to self-assembly on Au substrates. We use chemical lift-off lithography to singly and doubly pattern substrates. Selective antibody recognition of pre-functionalized thiols was comparable to or better than recognition of small molecules functionalized to alkanethiols after surface assembly. These findings demonstrate that synthesis and patterning approaches that circumvent sequential surface conjugation chemistries enable biomolecule recognition and afford gateways to multiplexed small-molecule functionalized substrates.

Pig identification and meat traceability by multiallelic amplification fragments with multiple single nucleotide polymorphisms.

Compared with conventional identification methods, DNA-based genetic approaches such as single nucleotide polymorphisms (SNPs) and satellites are much more reliable for pig identification and meat traceability. In this study, multiallelic amplification fragments with multiple SNPs, incorporating the advantages of both SNPs and microsatellites, were explored for the first time for pig identification and meat traceability. Primer pairs for multiallelic fragments and their optimal SNPs were successfully selected and used for identification of individuals from Suzhong and Duroc populations. Meanwhile, the combined panel of the above mentioned primer pairs together with their optimal SNPs for Suzhong and/or Duroc pigs were validated for identification of the hybrids (Suzhong×Duroc). Therefore, we have successfully selected multiallelic amplification fragments with multiple SNPs to identify pigs and their meat samples from Suzhong, Duroc or their hybrids. Our study demonstrates that our method is more powerful for pig identification or meat traceability than SNPs or microsatellites.

Patterning of supported gold monolayers via chemical lift-off lithography.

The supported monolayer of Au that accompanies alkanethiolate molecules removed by polymer stamps during chemical lift-off lithography is a scarcely studied hybrid material. We show that these Au-alkanethiolate layers on poly(dimethylsiloxane) (PDMS) are transparent, functional, hybrid interfaces that can be patterned over nanometer, micrometer, and millimeter length scales. Unlike other ultrathin Au films and nanoparticles, lifted-off Au-alkanethiolate thin films lack a measurable optical signature. We therefore devised fabrication, characterization, and simulation strategies by which to interrogate the nanoscale structure, chemical functionality, stoichiometry, and spectral signature of the supported Au-thiolate layers. The patterning of these layers laterally encodes their functionality, as demonstrated by a fluorescence-based approach that relies on dye-labeled complementary DNA hybridization. Supported thin Au films can be patterned via features on PDMS stamps (controlled contact), using patterned Au substrates prior to lift-off (e.g., selective wet etching), or by patterning alkanethiols on Au substrates to be reactive in selected regions but not others (controlled reactivity). In all cases, the regions containing Au-alkanethiolate layers have a sub-nanometer apparent height, which was found to be consistent with molecular dynamics simulations that predicted the removal of no more than 1.5 Au atoms per thiol, thus presenting a monolayer-like structure.

Sympathetic and parasympathetic innervation in hepatocellular carcinoma.

Autonomic nervous system plays an important role in the development of multiple cancers via regulating cancer cell proliferation, differentiation, apoptosis, migration and invasion. However, no detailed studies have been performed to study the role of autonomic nerve fibers in hepatocellular carcinoma (HCC) as well as its correlation with the progression of HCC. Here, we examined the distribution of the autonomic nerve fibers and analyzed the correlation between autonomic nerve fibers and the pathological characteristics of HCC patients. The transcriptional expression of adrenergic and cholinergic receptors was evaluated in both hepatoma cell lines and primary hepatoma cells. In addition, we summarized the function of receptors for neurotransmitters in different cancers recently reported. Our findings indicate that tissue of liver cancer is innervated by both sympathetic and parasympathetic nerves and the density of the nerve fibers is associated with patients' poor prognosis. Additionally, we report that adrenergic receptors ß2 and cholinergic receptors α7, M1 and M3 are high expressed in both hepatoma cell lines and primary hepatoma cells, indicating these receptors may play essential roles in the regulation of autonomic nervous system triggered HCC.

Diagnosis and prognosis-review of biomarkers for mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.

Tacrine-based Multifunctional Agents in Alzheimer's Disease: An Old Story in Continuous Development§.

BACKGROUND: The design of multifunctional agents represents one of the most active research field in medicinal chemistry. In particular, tacrine, a well known Acetylcholinesterase inhibitor, is one of the most used starting point to develop multifunctional ligands and hundreds of papers report about these new agents. This is the third review of a series concerning tacrinebased multifunctional ligands; in particular, in the present, we will summarize and discuss the most intriguing examples of tacrine-based multifunctional agents published since 2013 until 2016. METHODS: We analyzed the bibliographic databases for peer-reviewed publications concerning tacrine-based multifunctional agents possessing biological actions that go beyond the simple "cholinergic" blockage. These papers have been subdivided according to their biological activities. Since this is the third review of a series, we took into considerations only the papers appeared since 2013 until 2016. RESULTS: In this review, we have analyzed more than 33 papers. All the reported compounds retain good inhibitory activity towards acetyl- and butyryl-cholinesterase. The other biological activities concern mostly inhibition of a) ß-amyloid aggregation, b) ß-secretase, c) monoamino oxidases, modulation of τ and ROS and metal chelation. CONCLUSION: The analysis of the current literature reported in this review confirm the importance of tacrine as scaffold to develop multifunctional agents potentially usefull to contrast Alzheimer's disease. Furthermore, the compounds herein reported showed very intriguing biological activities that could be used as starting point to develop new compounds even more interesting and, hopefully, clinically usefull to contrast Alzheimer's Disease.

Surgical Treatment of Early l Stage Lung Cancer: What has Changed and What will Change in the Future.

Recent advances in the surgical treatment of early stage non-small cell lung cancer (NSCLC) have focused heavily on making procedures less invasive, less radical, and better tolerated. Advances in accuracy and increased utilization of cross-sectional imaging allows for diagnosis of smaller and more indolent tumors and preinvasive lesions. Similar to advanced disease, early-stage treatment is now being tailored to individual patients and their tumors. Sublobar resections are gaining acceptance as an oncologically equivalent approach to lobectomy in well-selected stage I patients. Minimally invasive approaches either by video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracic surgery are becoming the procedures of choice for anatomic NSCLC resections and provide decreased perioperative complications and increased tolerability, especially in the elderly and medically high-risk patients. Reports of even less invasive techniques including uniportal VATS and nonintubated lobar resections are now appearing in the literature.

Controlled DNA Patterning by Chemical Lift-Off Lithography: Matrix Matters.

Nucleotide arrays require controlled surface densities and minimal nucleotide-substrate interactions to enable highly specific and efficient recognition by corresponding targets. We investigated chemical lift-off lithography with hydroxyl- and oligo(ethylene glycol)-terminated alkanethiol self-assembled monolayers as a means to produce substrates optimized for tethered DNA insertion into post-lift-off regions. Residual alkanethiols in the patterned regions after lift-off lithography enabled the formation of patterned DNA monolayers that favored hybridization with target DNA. Nucleotide densities were tunable by altering surface chemistries and alkanethiol ratios prior to lift-off. Lithography-induced conformational changes in oligo(ethylene glycol)-terminated monolayers hindered nucleotide insertion but could be used to advantage via mixed monolayers or double-lift-off lithography. Compared to thiolated DNA self-assembly alone or with alkanethiol backfilling, preparation of functional nucleotide arrays by chemical lift-off lithography enables superior hybridization efficiency and tunability.