2D fin field-effect transistors integrated with epitaxial high-k gate oxide.

Precise integration of two-dimensional (2D) semiconductors and high-dielectric-constant (k) gate oxides into three-dimensional (3D) vertical-architecture arrays holds promise for developing ultrascaled transistors1-5, but has proved challenging. Here we report the epitaxial synthesis of vertically aligned arrays of 2D fin-oxide heterostructures, a new class of 3D architecture in which high-mobility 2D semiconductor fin Bi2O2Se and single-crystal high-k gate oxide Bi2SeO5 are epitaxially integrated. These 2D fin-oxide epitaxial heterostructures have atomically flat interfaces and ultrathin fin thickness down to one unit cell (1.2 nm), achieving wafer-scale, site-specific and high-density growth of mono-oriented arrays. The as-fabricated 2D fin field-effect transistors (FinFETs) based on Bi2O2Se/Bi2SeO5 epitaxial heterostructures exhibit high electron mobility (µ) up to 270 cm2 V-1 s-1, ultralow off-state current (IOFF) down to about 1 pA µm-1, high on/off current ratios (ION/IOFF) up to 108 and high on-state current (ION) up to 830 µA µm-1 at 400-nm channel length, which meet the low-power specifications projected by the International Roadmap for Devices and Systems (IRDS)6. The 2D fin-oxide epitaxial heterostructures open up new avenues for the further extension of Moore's law.

Graphene sandwich-based biological specimen preparation for cryo-EM analysis.

High-quality specimen preparation plays a crucial role in cryo-electron microscopy (cryo-EM) structural analysis. In this study, we have developed a reliable and convenient technique called the graphene sandwich method for preparing cryo-EM specimens. This method involves using two layers of graphene films that enclose macromolecules on both sides, allowing for an appropriate ice thickness for cryo-EM analysis. The graphene sandwich helps to mitigate beam-induced charging effect and reduce particle motion compared to specimens prepared using the traditional method with graphene support on only one side, therefore improving the cryo-EM data quality. These advancements may open new opportunities to expand the use of graphene in the field of biological electron microscopy.

Uniform thin ice on ultraflat graphene for high-resolution cryo-EM.

Cryo-electron microscopy (cryo-EM) visualizes the atomic structure of macromolecules that are embedded in vitrified thin ice at their close-to-native state. However, the homogeneity of ice thickness, a key factor to ensure high image quality, is poorly controlled during specimen preparation and has become one of the main challenges for high-resolution cryo-EM. Here we found that the uniformity of thin ice relies on the surface flatness of the supporting film, and developed a method to use ultraflat graphene (UFG) as the support for cryo-EM specimen preparation to achieve better control of vitreous ice thickness. We show that the uniform thin ice on UFG improves the image quality of vitrified specimens. Using such a method we successfully determined the three-dimensional structures of hemoglobin (64 kDa), α-fetoprotein (67 kDa) with no symmetry, and streptavidin (52 kDa) at a resolution of 3.5 Å, 2.6 Å and 2.2 Å, respectively. Furthermore, our results demonstrate the potential of UFG for the fields of cryo-electron tomography and structure-based drug discovery.

Ultraflat single-crystal hexagonal boron nitride for wafer-scale integration of a 2D-compatible high-κ metal gate.

Hexagonal boron nitride (hBN) has emerged as a promising protection layer for dielectric integration in the next-generation large-scale integrated electronics. Although numerous efforts have been devoted to growing single-crystal hBN film, wafer-scale ultraflat hBN has still not been achieved. Here, we report the epitaxial growth of 4 in. ultraflat single-crystal hBN on Cu0.8Ni0.2(111)/sapphire wafers. The strong coupling between hBN and Cu0.8Ni0.2(111) suppresses the formation of wrinkles and ensures the seamless stitching of parallelly aligned hBN domains, resulting in an ultraflat single-crystal hBN film on a wafer scale. Using the ultraflat hBN as a protective layer, we integrate the wafer-scale ultrathin high-κ dielectrics onto two-dimensional (2D) materials with a damage-free interface. The obtained hBN/HfO2 composite dielectric exhibits an ultralow current leakage (2.36 × 10-6 A cm-2) and an ultrathin equivalent oxide thickness of 0.52 nm, which meets the targets of the International Roadmap for Devices and Systems. Our findings pave the way to the synthesis of ultraflat 2D materials and integration of future 2D electronics.

Epitaxial Integration of Transferable High-κ Dielectric and 2D Semiconductor.

The synthesis of high-dielectric-constant (high-κ) dielectric materials and their integration with channel materials have been the key challenges in the state-of-the-art transistor architecture, as they can provide strong gate control and low operating voltage. For next-generation electronics, high-mobility two-dimensional (2D) layered semiconductors with dangling-bond-free surfaces and an atomic-thick thickness are being explored as channel materials to achieve shorter channel lengths and less interfacial scattering. Nowadays, the integration of high-κ dielectrics with high-mobility 2D semiconductors mainly relies on atomic layer deposition or transfer stacking, which may cause several undesirable problems, such as channel damage and interface traps. Here, we demonstrate the integration of high-mobility 2D semiconducting Bi2O2Se with transferable high-κ SrTiO3 as a 2D field-effect transistor by direct epitaxial growth. Remarkably, such 2D heterostructures can be efficiently transferred from the water-soluble Sr3Al2O6 sacrificial layer onto arbitrary substrates. The as-fabricated 2D Bi2O2Se/SrTiO3 transistors exhibit an on/off ratio over 104 and a subthreshold swing down to 90 mV/dec. Furthermore, the 2D Bi2O2Se/SrTiO3 heterostructures can be easily transferred onto flexible polyethylene terephthalate (PET) substrates, and the as-fabricated transistors exhibit good potential in flexible electronics. Our study opens up a new avenue for the integration of high-κ dielectrics with high-mobility 2D semiconductors and paves the way for the exploration of multifunctional electronic devices.

Strain-Free Layered Semiconductors for 2D Transistors with On-State Current Density Exceeding 1.3 mA µm-1.

High-mobility and air-stable two-dimensional (2D) Bi2O2Se semiconductor holds promise as an alternative fast channel material for next-generation transistors. However, one of the key challenges remaining in 2D Bi2O2Se is to prepare high-quality crystals to fabricate the high-performance transistors with a high on-state current density. Here, we present the free-standing growth of strain-free 2D Bi2O2Se crystals. An ultrahigh Hall mobility of 160 000 cm2 V-1 s-1 is measured in strain-free Bi2O2Se crystals at 2 K, which enables the observation of Shubnikov-de Haas quantum oscillations and shows substantially higher (>4 times) mobility over previous in-plane 2D crystals. The fabricated 2D transistors feature an on-off current ratio of ∼106 and a record-high on-state current density of ∼1.33 mA µm-1, which is comparable to that of commercial Si and Ge n-type field-effect transistors (FETs) for similar channel length. Strain-free 2D Bi2O2Se provides a promising material platform for studying novel quantum phenomena and exploration of high-performance low-power electronics.

Regulation by fungal endophyte of Rhodiola crenulata from enzyme genes to metabolites based on combination of transcriptome and metabolome.

BACKGROUND: The contents of some its crucial metabolites tend to decrease when Rhodiola crenulata is cultured at low altitude. Interestingly, it was found that an endophyte, Phialocephala fortinii, could alleviate this problem. RESULTS: There were 16 151 differential genes including 14 706 up-regulated and 1445 down-regulated unigenes with significant differences (P < 0.05), and a total of 1432 metabolites exhibited statistically significant (P < 0.05) metabolic differences comprising 27 different marker metabolites which showed highly significant values of VIP > 5 and P < 0.01. Results highlight differential regulation of 20 enzymatic genes that are involved in the biosynthesis of five different marker metabolites including acetaldehyde, homocysteine, cyclopropylamine, 1-pyrrolinium and halistanol sulfate. CONCLUSIONS: The positive physiological effect of P. fortinii on R. crenulata encompasses differential regulation in carbohydrate metabolism, lipid metabolism and secondary metabolite synthesis. © 2020 Society of Chemical Industry.

Integrated 2D multi-fin field-effect transistors.

Vertical semiconducting fins integrated with high-κ oxide dielectrics have been at the centre of the key device architecture that has promoted advanced transistor scaling during the last decades. Single-fin channels based on two-dimensional (2D) semiconductors are expected to offer unique advantages in achieving sub-1 nm fin-width and atomically flat interfaces, resulting in superior performance and potentially high-density integration. However, multi-fin structures integrated with high-κ dielectrics are commonly required to achieve higher electrical performance and integration density. Here we report a ledge-guided epitaxy strategy for growing high-density, mono-oriented 2D Bi2O2Se fin arrays that can be used to fabricate integrated 2D multi-fin field-effect transistors. Aligned substrate steps enabled precise control of both nucleation sites and orientation of 2D fin arrays. Multi-channel 2D fin field-effect transistors based on epitaxially integrated 2D Bi2O2Se/Bi2SeO5 fin-oxide heterostructures were fabricated, exhibiting an on/off current ratio greater than 106, high on-state current, low off-state current, and high durability. 2D multi-fin channel arrays integrated with high-κ oxide dielectrics offer a strategy to improve the device performance and integration density in ultrascaled 2D electronics.

Self-assembled superstructure alleviates air-water interface effect in cryo-EM.

Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (<100 kDa) at near-atomic resolution. This study expands the understanding of SAMs and provides a key to better control the interaction of protein with air-water interface.

Even-integer quantum Hall effect in an oxide caused by a hidden Rashba effect.

In the presence of a high magnetic field, quantum Hall systems usually host both even- and odd-integer quantized states because of lifted band degeneracies. Selective control of these quantized states is challenging but essential to understand the exotic ground states and manipulate the spin textures. Here we demonstrate the quantum Hall effect in Bi2O2Se thin films. In magnetic fields as high as 50 T, we observe only even-integer quantum Hall states, but there is no sign of odd-integer states. However, when reducing the thickness of the epitaxial Bi2O2Se film to one unit cell, we observe both odd- and even-integer states in this Janus (asymmetric) film grown on SrTiO3. By means of a Rashba bilayer model based on the ab initio band structures of Bi2O2Se thin films, we can ascribe the only even-integer states in thicker films to the hidden Rasbha effect, where the local inversion-symmetry breaking in two sectors of the [Bi2O2]2+ layer yields opposite Rashba spin polarizations, which compensate with each other. In the one-unit-cell Bi2O2Se film grown on SrTiO3, the asymmetry introduced by the top surface and bottom interface induces a net polar field. The resulting global Rashba effect lifts the band degeneracies present in the symmetric case of thicker films.

Nanoparticles-mediated ion channels manipulation: From their membrane interactions to bioapplications.

Ion channels are transmembrane proteins ubiquitously expressed in all cells that control various ions (e.g. Na+, K+, Ca2+ and Cl- etc) crossing cellular plasma membrane, which play critical roles in physiological processes including regulating signal transduction, cell proliferation as well as excitatory cell excitation and conduction. Abnormal ion channel function is usually associated with dysfunctions and many diseases, such as neurodegenerative disorders, ophthalmic diseases, pulmonary diseases and even cancers. The precise regulation of ion channels not only helps to decipher physiological and pathological processes, but also is expected to become cutting-edge means for disease treatment. Recently, nanoparticles-mediated ion channel manipulation emerges as a highly promising way to meet the increasing requirements with respect to their simple, efficient, precise, spatiotemporally controllable and non-invasive regulation in biomedicine and other research frontiers. Thanks the advantages of their unique properties, nanoparticles can not only directly block the pore sites or kinetics of ion channels through their tiny size effect, and perturb active voltage-gated ion channel by their charged surface, but they can also act as antennas to conduct or enhance external physical stimuli to achieve spatiotemporal, precise and efficient regulation of various ion channel activities (e.g. light-, mechanical-, and temperature-gated ion channels etc). So far, nanoparticles-mediated ion channel regulation has shown potential prospects in many biomedical fields at the interfaces of neuro- and cardiovascular modulation, physiological function regeneration and tumor therapy et al. Towards such important fields, in this typical review, we specifically outline the latest studies of different types of ion channels and their activities relevant to the diseases. In addition, the different types of stimulation responsive nanoparticles, their interaction modes and targeting strategies towards the plasma membrane ion channels will be systematically summarized. More importantly, the ion channel regulatory methods mediated by functional nanoparticles and their bioapplications associated with physiological modulation and therapeutic development will be discussed. Last but not least, current challenges and future perspectives in this field will be covered as well.

Structure of human phagocyte NADPH oxidase in the resting state.

Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation.

Elucidating the effect of biofertilizers on bacterial diversity in maize rhizosphere soil.

This study was conducted to investigate the effect of biofertilizers on the structure and diversity of the rhizosphere bacterial community of maize. Different biofertilizers were applied to maize. The physical and chemical properties of rhizosphere soil samples were analyzed and the rhizosphere bacteria were analyzed by 16S amplicon sequencing. The results showed that treatment with Bacillus licheniformis and B. amyloliquefaciens as biofertilizers increased the soil organic matter (SOM), total nitrogen, total phosphorus (TP), available phosphorus (AP), and available potassium (AK) contents, indicating that the plant growth-promoting rhizobacteria in the biofertilizers might help the host plant to produce root exudates that, in return, recruit beneficial communities due to available sugars, amino acids, organic acids, vitamins, and polymers. The rhizosphere of maize treated with B. subtilis biofertilizer had the highest diversity and richness. However, the rhizosphere treated with the combined bacterial strains had the lowest diversity and richness, which might be due to the directional increase of the abundance of some bacteria with special functions, but the decrease of the overall bacterial community diversity in the soil. The dominant bacterial phyla were Proteobacteria (32.2%-34.6%), Acidobacteria (15.0%-21.0%), Actinobacteria (13.1%-17.2%), and Gemmatimonadetes (9.0%-10.8%), and the dominant bacterial species were Aciditerrimonas ferrireducens JCM 15389 (4.3%-5.2%), Gemmatimonas aurantiaca (3.2%-4.1%), and Pyrinomonas methylaliphatogenes (2.1%-4.8%). The significantly enriched bacterial functions were associated with amino acid metabolism, sugar metabolism, and energy metabolism pathways. The results of a redundancy analysis showed that SOM, TP, and AK were the main factors affecting the microbial community structure in the maize rhizosphere. In conclusion, the application of biofertilizers increased the diversity and richness of the bacterial community in the maize rhizosphere soil. However, combined strain treatment was failed and not an ideal strategy due to the lowest abundance and diversity.

Circulating lead modifies hexavalent chromium-induced genetic damage in a chromate-exposed population: An epidemiological study.

Chromium (Cr) can coexist with other heavy metals in the blood of chronically chromate-exposed individuals. However, few studies have explored the health impacts of other hazardous metals after exposure to hexavalent chromium [Cr(VI)]. This study aimed to assess the modification effects of blood lead (Pb) on the genetic damage induced by Cr(VI). During 2010-2019, 1000 blood samples were collected from 455 workers exposed to chromate and 545 workers not exposed to chromate from the same factory with similar labor intensity. The levels of Cr and Pb were measured in whole blood samples. Micronucleus frequency (MNF) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured to reflect different types of genetic damage. Multivariate linear regression analyses were performed to evaluate the associations between hazardous metals and the modification effects of Pb on genetic damage. The geometric mean levels of Cr and Pb in the exposure group were significantly higher than those in the control group [Cr: 6.42 (6.08- 6.79) vs. 1.29 (1.22- 1.36) µg/L; Pb: 38.82 (37.22- 40.50) vs. 34.47 (33.15- 35.85) µg/L]. The geometric means of urinary 8-OHdG and MNF in exposure group were 4.00 (3.64- 4.40) µg/g and 5.40 (4.89- 5.97) ‰, respectively, significantly higher than the 3.20 (2.94- 3.48) µg/g and 4.57 (4.15- 5.03) ‰, respectively, in control group. log2Cr was independently and positively associated with urinary 8-OHdG (ß-adjusted = 0.143, 95% CI: 0.082- 0.204) and MNF (ß-adjusted = 0.303, 95%CI: 0.020- 0.587). With the change in circulating Pb levels, the types of genetic damage induced by Cr(VI) were different. At low levels of circulating Pb (<30.80 µg/L), chromate mainly caused changes in 8-OHdG, while at high circulating Pb levels (≥44.88 µg/L), chromate induced alterations in MNF. The findings suggested that chromate exposure could cause multiple types of genetic damage, and circulating Pb might modify the association between circulating Cr and the form of genetic damage.

Atomically Thin Bilayer Janus Membranes for Cryo-electron Microscopy.

Cryo-electron microscopy (cryo-EM) has emerged as a vital tool to reveal the native structure of beam-sensitive biomolecules and materials. Yet high-resolution cryo-EM analysis is still limited by the poorly controlled specimen preparation and urgently demands a robust supporting film material to prepare desirable samples. Here, we developed a bilayer Janus graphene membrane with the top-layer graphene being functionalized to interact with target molecules on the surface, while the bottom layer being kept intact to reinforce its mechanical steadiness. The ultraclean and atomically thin bilayer Janus membrane prepared by our protocol on one hand generates almost no extra noise and on the other hand reduces the specimen motion during cryo-EM imaging, thus allowing the atomic-resolution characterization of surface functional groups. Using such Janus membranes in cryo-EM specimen preparation, we were able to directly image the lithium dendrite and reconstruct macromolecules at near-atomic resolution. Our results demonstrate the bilayer Janus design as a promising supporting material for high-resolution cryo-EM and EM imaging.

Robust ultraclean atomically thin membranes for atomic-resolution electron microscopy.

The fast development of high-resolution electron microscopy (EM) demands a background-noise-free substrate to support the specimens, where atomically thin graphene membranes can serve as an ideal candidate. Yet the preparation of robust and ultraclean graphene EM grids remains challenging. Here we present a polymer- and transfer-free direct-etching method for batch fabrication of robust ultraclean graphene grids through membrane tension modulation. Loading samples on such graphene grids enables the detection of single metal atoms and atomic-resolution imaging of the iron core of ferritin molecules at both room- and cryo-temperature. The same kind of hydrophilic graphene grid allows the formation of ultrathin vitrified ice layer embedded most protein particles at the graphene-water interface, which facilitates cryo-EM 3D reconstruction of archaea 20S proteasomes at a record high resolution of ~2.36 Å. Our results demonstrate the significant improvements in image quality using the graphene grids and expand the scope of EM imaging.

Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy.

OBJECTIVES: Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose. METHODS: Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated. RESULTS: The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05). CONCLUSION: The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.

Determination of ephedrine and related compounds in pharmaceutical preparations by ion chromatography with direct conductivity detection.

An ion chromatographic method with conductivity detection for the simultaneous determination of ephedrine, pseudoephedrine and norephedrine was developed. A mixture of 2.0 mmol/L HNO3 and 2% (v/v) acetonitrile was used as eluent. The three ephedrine-like compounds were separated and determined within 20 min. The linear ranges were 0.08-50 microg/mL for ephedrine, 0.08-40 microg/mL for pseudoephedrine and 0.06-40 microg/mL for norephedrine. The detection limits were 0.03 microg/mL for ephedrine and pseudoephedrine, and 0.02 microg/mL for norephedrine. The method has been applied successfully to the determination of these sympathomimetics in pharmaceutical preparations and in Ephedra herbs.