Highly visible-light-active sulfur and carbon co-doped TiO2 (SC-TiO2) heterogeneous photocatalysts prepared by underwater discharge plasma.

To promptly and simply create highly crystalline S/C co-doped TiO2 (SC-TiO2) photocatalysts at room temperature and atmospheric pressure, we suggest a novel plasma-assisted sol-gel synthesis method. This method is a simultaneous synthetic process, in which an underwater plasma undergoes continuous reactions to generate high-energy atomic and molecular species that enable TiO2 to achieve crystallinity, a large surface area, and a heterogeneous structure within a few minutes. In particular, it was demonstrated that the heterogeneously structured TiO2 was formed by doping that sulfur and carbon replace O or Ti atoms in the TiO2 lattice depending on the composition of the synthesis solution during underwater plasma treatment. The resultant SC-TiO2 photocatalysts had narrowed bandgap energies and extended optical absorption scope into the visible range by inducing the intermediate states within bandgap due to generation of oxygen vacancies on the surface of TiO2 through synthesis, crystallization, and doping. Correspondingly, SC-TiO2 showed a significant degradation efficiency ([k] = 6.91 h-1) of tetracycline (TC, antibiotics) under solar light irradiation, up to approximately 4 times higher compared to commercial TiO2 ([k] = 1.68 h-1), resulting in great water purification. Therefore, we anticipate that this underwater discharge plasma system will prove to be an advantageous technique for producing heterostructural TiO2 photocatalysts with superior photocatalytic efficiency for environmental applications.

Serial Circulating Tumor DNA Analysis with a Tumor-Naïve Next-Generation Sequencing Panel Detects Minimal Residual Disease and Predicts Outcome in Ovarian Cancer.

Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment. SIGNIFICANCE: In ovarian cancer, serial circulating tumor DNA testing is a highly predictive marker of patient survival, with a significantly improved recurrence detection lead time compared with conventional monitoring tools.

Reinforcing Synaptic Plasticity of Defect-Tolerant States in Alloyed 2D Artificial Transistors.

While two-dimensional (2D) materials possess the desirable future of neuromorphic computing platforms, unstable charging and de-trapping processes, which are inherited from uncontrollable states, such as the interface trap between nanocrystals and dielectric layers, can deteriorate the synaptic plasticity in field-effect transistors. Here, we report a facile and effective strategy to promote artificial synaptic devices by providing physical doping in 2D transition-metal dichalcogenide nanomaterials. Our experiments demonstrate that the introduction of niobium (Nb) into 2D WSe2 nanomaterials produces charge trap levels in the band gap and retards the decay of the trapped charges, thereby accelerating the artificial synaptic plasticity by encouraging improved short-/long-term plasticity, increased multilevel states, lower power consumption, and better symmetry and asymmetry ratios. Density functional theory calculations also proved that the addition of Nb to 2D WSe2 generates defect tolerance levels, thereby governing the charging and de-trapping mechanisms of the synaptic devices. Physically doped electronic synapses are expected to be a promising strategy for the development of bioinspired artificial electronic devices.

Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study.

Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.

Environmentally Stable and Reconfigurable Ultralow-Power Two-Dimensional Tellurene Synaptic Transistor for Neuromorphic Edge Computing.

While neuromorphic computing can define a new era for next-generation computing architecture, the introduction of an efficient synaptic transistor for neuromorphic edge computing still remains a challenge. Here, we envision an atomically thin 2D Te synaptic device capable of achieving a desirable neuromorphic edge computing design. The hydrothermally grown 2D Te nanosheet synaptic transistor apparently mimicked the biological synaptic nature, exhibiting 100 effective multilevel states, a low power consumption of ∼110 fJ, excellent linearity, and short-/long-term plasticity. Furthermore, the 2D Te synaptic device achieved reconfigurable MNIST recognition accuracy characteristics of 88.2%, even after harmful detergent environment infection. We believe that this work serves as a guide for developing futuristic neuromorphic edge computing.

Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer.

Purpose: Cervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients. Materials and methods: Preoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes. Results: Cervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. Conclusion: Cervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.

Subgrouping Automata: automatic sequence subgrouping using phylogenetic tree-based optimum subgrouping algorithm.

Sequence subgrouping for a given sequence set can enable various informative tasks such as the functional discrimination of sequence subsets and the functional inference of unknown sequences. Because an identity threshold for sequence subgrouping may vary according to the given sequence set, it is highly desirable to construct a robust subgrouping algorithm which automatically identifies an optimal identity threshold and generates subgroups for a given sequence set. To meet this end, an automatic sequence subgrouping method, named 'Subgrouping Automata' was constructed. Firstly, tree analysis module analyzes the structure of tree and calculates the all possible subgroups in each node. Sequence similarity analysis module calculates average sequence similarity for all subgroups in each node. Representative sequence generation module finds a representative sequence using profile analysis and self-scoring for each subgroup. For all nodes, average sequence similarities are calculated and 'Subgrouping Automata' searches a node showing statistically maximum sequence similarity increase using Student's t-value. A node showing the maximum t-value, which gives the most significant differences in average sequence similarity between two adjacent nodes, is determined as an optimum subgrouping node in the phylogenetic tree. Further analysis showed that the optimum subgrouping node from SA prevents under-subgrouping and over-subgrouping.

A programmable Escherichia coli consortium via tunable symbiosis.

Synthetic microbial consortia that can mimic natural systems have the potential to become a powerful biotechnology for various applications. One highly desirable feature of these consortia is that they can be precisely regulated. In this work we designed a programmable, symbiotic circuit that enables continuous tuning of the growth rate and composition of a synthetic consortium. We implemented our general design through the cross-feeding of tryptophan and tyrosine by two E. coli auxotrophs. By regulating the expression of genes related to the export or production of these amino acids, we were able to tune the metabolite exchanges and achieve a wide range of growth rates and strain ratios. In addition, by inverting the relationship of growth/ratio vs. inducer concentrations, we were able to "program" the co-culture for pre-specified attributes with the proper addition of inducing chemicals. This programmable proof-of-concept circuit or its variants can be applied to more complex systems where precise tuning of the consortium would facilitate the optimization of specific objectives, such as increasing the overall efficiency of microbial production of biofuels or pharmaceuticals.

Microdroplet-enabled highly parallel co-cultivation of microbial communities.

Microbial interactions in natural microbiota are, in many cases, crucial for the sustenance of the communities, but the precise nature of these interactions remain largely unknown because of the inherent complexity and difficulties in laboratory cultivation. Conventional pure culture-oriented cultivation does not account for these interactions mediated by small molecules, which severely limits its utility in cultivating and studying "unculturable" microorganisms from synergistic communities. In this study, we developed a simple microfluidic device for highly parallel co-cultivation of symbiotic microbial communities and demonstrated its effectiveness in discovering synergistic interactions among microbes. Using aqueous micro-droplets dispersed in a continuous oil phase, the device could readily encapsulate and co-cultivate subsets of a community. A large number of droplets, up to ∼1,400 in a 10 mm × 5 mm chamber, were generated with a frequency of 500 droplets/sec. A synthetic model system consisting of cross-feeding E. coli mutants was used to mimic compositions of symbionts and other microbes in natural microbial communities. Our device was able to detect a pair-wise symbiotic relationship when one partner accounted for as low as 1% of the total population or each symbiont was about 3% of the artificial community.

Simultaneous synthesis of 2-phenylethanol and L-homophenylalanine using aromatic transaminase with yeast Ehrlich pathway.

2-Phenylethanol is a widely used aroma compound with rose-like fragrance and L-homophenylalanine is a building block of angiotensin-converting enzyme (ACE) inhibitor. 2-phenylethanol and L-homophenylalanine were synthesized simultaneously with high yield from 2-oxo-4-phenylbutyric acid and L-phenylalanine, respectively. A recombinant Escherichia coli harboring a coupled reaction pathway comprising of aromatic transaminase, phenylpyruvate decarboxylase, carbonyl reductase, and glucose dehydrogenase (GDH) was constructed. In the coupled reaction pathway, the transaminase reaction was coupled with the Ehrlich pathway of yeast; (1) a phenylpyruvate decarboxylase (YDR380W) as the enzyme to generate the substrate for the carbonyl reductase from phenylpyruvate (i.e., byproduct of the transaminase reaction) and to shift the reaction equilibrium of the transaminase reaction, and (2) a carbonyl reductase (YGL157W) to produce the 2-phenylethanol. Selecting the right carbonyl reductase showing the highest activity on phenylacetaldehyde with narrow substrate specificity was the key to success of the constructing the coupling reaction. In addition, NADPH regeneration was achieved by incorporating the GDH from Bacillus subtilis in the coupled reaction pathway. Based on 40 mM of L-phenylalanine used, about 96% final product conversion yield of 2-phenylethanol was achieved using the recombinant E. coli.