Multiple heteroatom substitution effect on destructive quantum interference in tripodal single-molecule junctions.

Quantum interference (QI) has been identified as a promising strategy for designing molecular-scale electronic devices. Heteroatom doping can effectively tailor the local structures and electronic states of intrinsic molecules, and endow them with modified electron transport properties. Herein, the impacts of multiple heteroatom substitution on destructive quantum interference (DQI) have been investigated based on tripodal meta-linked phenyl derivatives. Orbital views based on the Hückel method qualitatively predict the meta-anchored molecules with DQI features, while the introduction of nitrogen atoms can alleviate the suppression of DQI at the Fermi level (EF). This is generally consistent with the movement or even removal of the antiresonance dips in transmission spectra. The substituent on position 2 can raise the antiresonance energy, while the substituent on position 4 or 6 can lower the antiresonance energy. When more than one nitrogen atom is incorporated, the impact of the substitution on positions 4 and 6 can be superimposed and the substitution on positions 2 and 4 can be partly cancelled. The experimental single-molecule conductance for tripodal molecules follows the trend of 0N-3SMe < 1N-3SMe < 3N-3SMe < 2N-3SMe, in agreement with the theoretical prediction. Additionally, the regulation is the intrinsic property depending on the position and number of the nitrogen atoms in the backbone and is irrelevant to the number and type of the anchoring groups. Our findings provide qualitative guidance for tuning the electron transport based on DQI in heterocycle molecular devices.

Rapid titration with oral sustained-release morphine plus subcutaneous morphine in a multi-center, randomized control study of cancer patients with moderate to severe cancer pain.

BACKGROUND: Pain is one of the most common concomitant symptoms among cancer patients. Pharmacologic agents are regarded as a cornerstone of cancer pain management. 'Dose titration' with short-acting morphine is widely accepted. Such a titration method is very complicated. The analgesic background establishment is often delayed. Titration based on sustained-release opioids is also recommended, but the onset of analgesic effect requires hours, whereas the rescue analgesia is always needed. This study evaluated the optimized morphine titration scheme with a simultaneous combination of sustained-release morphine and subcutaneous morphine. METHODS: In a multicenter, 7-day, randomized controlled study, patients with moderate to severe cancer pain were assigned to receive either sustained-release morphine and subcutaneous morphine simultaneously (rapid titration) or only subcutaneous morphine to dose titration. The primary outcome was the safety and the number of times of rescue therapy as needed in the first 24 h. RESULTS: A total of 108 patients with moderate to severe cancer pain were included in the study. The number of times of rescue analgesics in the first 24 h significantly reduced in the rapid titration group (0.4 ± 0.48 vs. 2.3 ± 0.78, P = 0.000). No differences in the intensity of opioid-related symptoms were found between the two groups. CONCLUSIONS: Rapid titration is safe and efficient, which could significantly decrease rescue analgesics in the first 24 h and achieve better analgesic efficacy for cancer pain patients.

Robotic laser position versus freehand in CT-guided percutaneous microwave ablation for single hepatocellular carcinoma (diameter < 3 cm): a preliminary study.

PURPOSE: To compare the accuracy and safety of robotic laser position (RLP) versus freehand for antenna CT-guided microwave ablation (MWA) of single hepatocellular carcinoma (HCC) (diameter < 3 cm). MATERIALS AND METHODS: This retrospective study was conducted between May 2020 and June 2021. A total of 40 patients with early HCC who underwent CT-guided MWA were divided into two groups: a freehand group (n = 20) and a RLP group (n = 20). Based on in-plane and out-of-plane data, the actual puncture point error (APPE), number of repositioning procedures, and operative duration were compared using the Mann-Whitney U test. Ablation-related complications were compared using the Chi-squared test. RESULTS: The mean diameter of HCC patients who received MWA was 2.4 ± 0.5 cm. For in-plane APPE, APPE was comparable between the two groups (p = 0.299). However, for the out-of-plane position, the APPE in the freehand group was higher than that in the RLP group (p = 0.027). The number of repositioning procedures was 0 (range, 0-0) for RLP-guided procedures and 3 (range, 2-5) for freehand procedures, showing a statistically significant difference between the two groups (p < 0.001). The mean operative duration for freehand procedures was 39 min, compared with 26 min for RLP-guided procedures, showing a significant difference (p = 0.013). No deaths or major complications were directly related to MWA. Minor complications in the freehand group were comparable with those in the RLP group (p = 0.313). CONCLUSION: RLP guidance significantly reduces the number of antenna repositioning procedures in MWA and improves puncture accuracy for target HCC out-of-plane. In addition, the operative duration of robotic guidance was shorter than that of freehand guidance.

E3 ubiquitin ligase PJA1 regulates lung adenocarcinoma apoptosis and invasion through promoting FOXR2 degradation.

Among all lung cancer cases, lung adenocarcinoma (LAC) represents nearly 40% and remains the leading cause of cancer deaths worldwide. Although the combination therapy of surgical treatment with radiotherapy, chemotherapy, and immunotherapy, has been used to treat LAC, unfortunately, high recurrence rates and poor survival remain. Therefore, novel prognostic markers and new targets for molecular targeted therapy in LAC is urgently needed. Fork-head box R2 (FOXR2) plays a key role in a wide range of cellular processes, including cellular proliferation, invasion, differentiation, and apoptosis, and it has been reported to be implicated in progression of LAC, thus inhibition of FOXR2 may be a novel targeting therapy for lung cancer. This current study found that E3 ligase PJA1 regulates ubiquitin-mediated degradation of FOXR2 and predicts good outcome of patients with LAC. In addition, it was showed force expression of PJA1 significantly inhibited LAC cells invasion and induced apoptosis in vitro through inactivating Wnt/ß-catenin signaling pathway. In short, our findings reveal that PJA1 could be a potential diagnostic and prognostic biomarkers and the PJA1- FOXR2 axis could be served as a promising target for LAC therapy.

How do government subsidies promote new energy vehicle diffusion in the complex network context? A three-stage evolutionary game model.

In order to cope with the impact of current coronavirus disease 2019 (COVID-19), the continued extension of financial subsidy period for new energy vehicles at the national level is a strong measure to support the sustainable development of new energy vehicle (NEV) industry. This paper further explores the promotion impact of government subsidies on NEV diffusion, and establishes a three-stage evolutionary game model. Based on the actual application, the NEV diffusion process is simulated in four kinds of authoritative networks. Results show that: (1) in the scale-free network, the subsidy rate must be high enough to promote full NEV diffusion, and the larger the network scale, the higher the threshold of subsidy rate; (2) in the small-world network, the larger the network scale, the more beneficial it is for full NEV diffusion; (3) for the small-scale network, topological characteristics have little effect on NEV diffusion depth, and only affect the speed when NEV diffusion reaches the stable state; (4) for the large-scale network, NEV diffusion in the scale-free network is more sensitive to the subsidy rate than that in the small-world network; (5) network topologies influencing NEV diffusion can be divided into two priorities. Finally, relevant policy recommendations are presented.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms.

We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.

Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020.

To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.

RNF115-mediated ubiquitination of p53 regulates lung adenocarcinoma proliferation.

Lung adenocarcinoma (LAC) represents approximately 40% of all lung cancer cases and is the leading cause of cancer-associated mortality worldwide. Although combined treatment, including radiotherapy, chemotherapy, surgical treatment and immunotherapy, has been used in treating LAC, the five-year survival rate of patients with LAC has not significantly improved. Therefore, it is vital for cancer research to investigate novel prognostic markers and new targets for molecular targeted therapy in LAC. TP53 is an important tumor suppressor gene and is frequently inactivated in lung cancer, thus upregulation or activation of p53 may be a novel targeted therapy for LAC. The present study found that RNF115 mediates ubiquitination of p53 and predicts poor prognosis of patients with LAC. Functionally, it was demonstrated that disruption of RNF115 significantly inhibited cell viability in vitro through inducing G1 phase arrest of LAC cells, which reduced tumor growth in an xenograft model. Taken together, these results suggest that RNF115 could be a novel prognostic biomarker and the RNF115-p53 axis may be a potential target for LAC therapy.

Impact of Dwell Time of Retrievable IVC Filters on IVC Lumen Diameter: A Series of 36 Cases.

BACKGROUND: Inferior vena cava (IVC) filters are effective in preventing pulmonary embolism in patients at risk. This study aimed to investigate whether the dwell time of retrievable IVC filters have impact on IVC lumen diameter. METHODS: The clinical data of 36 patients treated with retrievable IVC filters from January 2016 to November 2018 were retrospectively collected. A total of 33 filters were successfully removed. At times of filter placement and removal, the IVC lumen diameter (at upper, middle, and lower levels of the filter), distance between the filter upper end and the right renal vein opening, and degree of filter tilt were measured. RESULTS: IVC filters were placed because of deep vein thrombosis in the lower limbs after fractures in 26 patients. The median dwell time of the IVC filters was 18 days. From the time of filter placement to that of removal, the IVC diameter decreased significantly at the middle (28.07 ± 5.92 vs. 25.73 ± 7.33 mm, P = 0.002) and lower levels (27.48 ± 4.73 vs. 26.36 ± 4.72 mm, P = 0.003) of the filters. No significant difference was noticed in the IVC diameter at the upper levels of the filters (27.78 ± 6.43 vs. 27.11 ± 6.63 mm, P = 0.082). Positive correlation was noticed between filter dwell time and IVC diameter changes at the upper (r = 0.381, P = 0.029) and middle (r = 0.555, P = 0.001) levels of the filters. No significant change was noticed in the distance from the filter upper end to the right renal vein opening and the degree of filter tilt. CONCLUSIONS: Retrievable IVC filters are associated with IVC stenosis. The severity of IVC stenosis is positively correlated with the dwell time of filters.

Theoretical study on the charge transport properties of three series of dicyanomethylene quinoidal thiophene derivatives.

It is very important to analyse the most advantageous connection style for quinoidal thiophene derivatives, which are used in n-type organic semiconductor transport materials. In the present work, the charge transport properties of three series of quinoidal thiophene derivatives, oligothiophene (series A), thienothiophene (series B) and benzothiophene (series C), are systematically investigated by employing full quantum charge transfer theory combined with kinetic Monte-Carlo simulation. The single crystal structures of the molecules we had constructed were predicted using the USPEX program combined with density functional theory (DFT) and considering the dispersion corrected. Our theoretical results expounded how the different connection styles, including oligo-, thieno-, and benzo-thiophene in the quinoidal thiophenes derivatives, effectively tune their electronic structures, and revealed how their intermolecular interactions affect the molecular packing patterns and hence their charge transport properties by symmetry-adapted perturbation theory (SAPT). In the meantime we also elucidated the role of end-cyano groups in noncovalent interactions. Furthermore, it is clarified that quinoidal thiophene derivatives show excellent carrier transport properties due to their optimal molecular stacking motifs and larger electronic couplings besides their low energy gap. In addition, our theoretical results demonstrate that quinoidal oligothiophene derivatives (n = 3-5) with more thiophene rings will have ambipolar transport properties, so quinoidal thienothiophene and benzothiophene derivatives should be promising alternatives as n-type OSCs. When we focused only on the electronic transport properties in the three series of molecules, quinoidal benzothiophene derivatives were slightly better than quinoidal oligothiophene or thienothiophene derivatives.

Theoretical Investigations into the Electron and Ambipolar Transport Properties of Anthracene-Based Derivatives.

To obtain anthracene-based derivatives with electron transport behavior, two series of anthracene-based derivatives modified by trifluoromethyl groups (-CF3) and cyano groups (-CN) at the 9,10-positions of the anthracene core were studied. Their electronic structures and crystal packings were also analyzed and compared. The charge-carrier mobilities were evaluated by quantum nuclear tunneling theory based on the incoherent charge-hopping model. Our results suggest that introducing -CN groups at 9,10-positions of the anthracene core is more favorable than introducing -CF3 to maintain great planar rigidity of the anthracene skeleton, decreasing more lowest unoccupied molecular orbital energy levels (0.45-0.55 eV), reducing reorganization energies, and especially forming a tight packing motif. Eventually, the excellent electron transport materials could be obtained. The molecule 1-B in Series 1 containing -CF3 groups is an ambipolar organic semiconductor (OSC) material with a 2D transport network, and its value of µh-max/µe-max is 1.75/0.47 cm2 V-1 s-1 along different directions; 2-A and 2-C in Series 2 with -CN groups are excellent n-type OSC candidates with the maximum intrinsic mobilities of 3.74 and 2.69 cm2 V-1 s-1 along the π-π stacking direction, respectively. Besides, the Hirshfeld surface and quantum theory of atoms in molecules analyses were applied to reveal the relationship between noncovalent interactions and crystal stacking.

Genome sequencing of Aureobasidium pullulans P25 and overexpression of a glucose oxidase gene for hyper-production of Ca2+-gluconic acid.

Gluconic acid (GA) has many applications such as in the food and pharmaceutical industry. Aureobasidium pullulans P25 strain is able to produce high levels of Ca2+-GA. The genome length, GC content and the gene number of this yeast were found to be 30.97 Mb, 50.28% and 10,922, respectively. The pathways for gluconic acid biosynthesis were annotated. Glucose oxidase (Gox) sequences from different strains of A. pullulans were highly similar but were distinct from those of other fungi. The glucose oxidase had two FAD binding sites and a signal sequence. Deletion of the GOX gene resulted in a strain that showed no Gox activity and that was unable to produce Ca2+-GA. Overexpression of the GOX gene in strain P25 generated strain GA-6 that produced 200.2 ± 2.3 Ca2+-GA g/l and 2480 U/mg of Gox activity. The productivity of Ca2+-GA was 2.78 g/l/h and the yield was 1.1 g/g.

Theoretical study on the charge transport in single crystals of TCNQ, F2-TCNQ and F4-TCNQ.

2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ) was recently reported to display excellent electron transport properties in single crystal field-effect transistors (FETs). Its carrier mobility can reach 25 cm2 V-1 s-1 in devices. However, its counterparts TCNQ and F4-TCNQ (tetrafluoro-7,7,8,8-tetracyanoquinodimethane) do not exhibit the same highly efficient behavior. To better understand this significant difference in charge carrier mobility, a multiscale approach combining semiclassical Marcus hopping theory, a quantum nuclear enabled hopping model and molecular dynamics simulations was performed to assess the electron mobilities of the Fn-TCNQ (n = 0, 2, 4) systems in this work. The results indicated that the outstanding electron transport behavior of F2-TCNQ arises from its effective 3D charge carrier percolation network due to its special packing motif and the nuclear tunneling effect. Moreover, the poor transport properties of TCNQ and F4-TCNQ stem from their invalid packing and strong thermal disorder. It was found that Marcus theory underestimated the mobilities for all the systems, while the quantum model with the nuclear tunneling effect provided reasonable results compared to experiments. Moreover, the band-like transport behavior of F2-TCNQ was well described by the quantum nuclear enabled hopping model. In addition, quantum theory of atoms in molecules (QTAIM) analysis and symmetry-adapted perturbation theory (SAPT) were used to characterize the intermolecular interactions in TCNQ, F2-TCNQ and F4-TCNQ crystals. A primary understanding of various noncovalent interaction responses for crystal formation is crucial to understand the structure-property relationships in organic molecular materials.

Emerging New Phylogenetic Groups of Rabies Virus in Chinese Ferret Badgers.

Chinese ferret badger (FB)-transmitted rabies is a serious threat to public health in southeast China. Although mostly associated with dogs, the rabies virus (RABV) presents genetic diversity and has a significantly wide host range in China. Instead of the dog- and wildlife-associated China II lineage in the past decades, the China I lineage has become the main epidemic group hosted and transmitted by dogs. In this study, four new lineages, including 43 RABVs from FBs, have been classified within the dog-dominated China I lineage since 2014. FB RABVs have been previously categorized in the China II lineage. Moreover, FB-hosted viruses seem to have become the main independent FB-associated clade in the phylogenetic tree. This claim suggests that the increasing genetic diversity of RABVs in FBs is a result of the selective pressure from coexisting dog rabies. FB transmission has become complicated and serious with the coexistence of dog rabies. Therefore, apart from targeting FB rabies, priority should be provided by the appropriate state agencies to perform mass immunization of dog against rabies.

Possible Transmission of Irkut Virus from Dogs to Humans.

Lyssaviruses, including Rabies virus, Duvenhage virus, European bat lyssavirus 1, European bat lyssavirus 2, Australian bat lyssavirus, and Irkut virus (IRKV), have caused human fatalities, but infection of IRKV in dogs has not been previously reported. In China, a dead dog that previously bit a human was determined to be infected with IRKV. Pathogenicity tests revealed that IRKVs can cause rabies-like disease in dogs and cats after laboratory infection. The close relationship between humans and pets, such as dogs and cats, may generate a new spillover-spreading route for IRKV infection. Therefore, additional attention should be paid to trans-species infection of IRKV between bats and dogs or dogs and humans through investigation of the prevalence and circulation patterns of IRKV in China.

Comparison of immune responses to attenuated rabies virus and street virus in mouse brain.

Rabies is a lethal neurological disease caused by the neurotropic rabies virus (RABV). To investigate the innate immune response in the brain during rabies infection, key gene transcripts indicative of innate immunity in a mouse model system were measured using real-time RT-PCR. Mice were infected via the intracerebral or intramuscular route with either attenuated rabies virus (SRV9) or pathogenic rabies virus (BD06). Infection with SRV9 resulted in the early detection of viral replication and the rapid induction of innate immune response gene expression in the brain. BD06 infection elicited innate immune response gene expression during only the late stage of infection. We measured Na-fluorescein uptake to assess blood-brain barrier (BBB) permeability, which was enhanced during the early stage of SRV9 infection and significantly enhanced during the late stage of BD06 infection. Furthermore, early SRV9 replication increased the maturation and differentiation of dendritic cells (DCs) and B cells in the inguinal lymph nodes and initiated the generation of virus-neutralizing antibodies (VNAs), which cooperate with the innate immune response to eliminate virus from the CNS. However, BD06 infection did not stimulate VNA production; thus, the virus was able to evade the host immune response and cause encephalitis. The rabies virus phosphoprotein has been reported to counteract IFN activation. In an in vitro study of the relationship between IFN antagonism and RABV pathogenicity, we demonstrated that SRV9 more strongly antagonized IFN activity than did BD06. Therefore, there is no positive relationship between the IFN antagonist activity of the virus and its pathogenicity.

Theoretical investigations into the charge transfer properties of thiophene α-substituted naphthodithiophene diimides: excellent n-channel and ambipolar organic semiconductors.

A theoretical study was carried out to investigate the electronic structures and the charge transport properties of a series of naphthodithiophene diimide (NDTI) thiophene α-substituted derivatives NDTI-X using density functional theory and classical Marcus charge transfer theory. This study deeply revealed the structure-property relationships by analyzing the intermolecular interactions in crystal structures of C8-NDTI and C8-NDTI-Cl thoroughly by using the Hirshfeld surface, QTAIM theories and symmetry-adapted perturbation theory (SAPT). Our results suggested that a 2-D brick-like π-stacking structure makes C8-NDTI-Cl a more excellent n-type semiconducting material with µmax-e of 2.554 cm2 V-1 s-1 than C8-NDTI with a herringbone-like slipped π-stacking motif. In addition, the calculated results showed that by modifying the thiophene α-positions of NDTI with electron-withdrawing substituents, -F, -Cl and -CN, low-lying LUMO energy levels and a high adiabatic electron affinity EA(a) can be obtained; while introducing electron-donating groups, benzene (-B), thiophene (-T), benzo[b]thiophene (-BT) and naphtha[2,3-b]thiophene (-NT), expanded the molecular π-conjugated backbone, and narrow band gaps, high EA(a) and small reorganization energies can be obtained. Theoretical simulations predict that NDTI-CN is an excellent air-stable n-type organic semiconducting material with an average electron mobility µe of up to 1.743 cm2 V-1 s-1. Owing to their high EA(a), moderate adiabatic ionization potential IP(a) as well as small hole and electron reorganization energies, NDTI-BT and NDTI-NT are two well-balanced air-stable ambipolar semiconducting materials. The theoretical average hole/electron mobilities are as high as 2.708/3.739 cm2 V-1 s-1 for C8-NDTI-NT and 1.597/2.350 cm2 V-1 s-1 for C8-NDTI-BT, respectively.

Dog-transmitted Rabies in Beijing, China.

Rabies remains a continuous threat to public health in Beijing. In this study, a total of 224 brain tissues were collected from suspected infected stray dogs within Beijing between January 2015 and December 2016. Among them, total of 67 samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies in Beijing is currently a relatively independent public health issue originating from local rabid dogs apart from the imported cases from elsewhere in the country. Because vaccination of unregistered dogs against rabies is still neglected in Beijing and other regions of China, national and local authorities should play central roles in all related aspects, such as development of policies, engagement of stakeholders for public and professional education, entire vaccination process, and animal management.

Pseudorabies in farmed foxes fed pig offal in Shandong province, China.

Pseudorabies (PR, Aujeszky's disease) is an acute, highly contagious viral disease resulting in major economic losses to the swine industry. PR is endemic in wild and domestic animals, although its natural host is the pig. Here, we report an outbreak of PR in foxes on a fur-producing farm in Yuncheng county, Shandong, China, that were fed pig offal. The diagnosis of PR was based on nervous signs and standard PCR methods and by isolation of PRV from fox brain tissue in Vero cells. The diagnosis was confirmed by an indirect immunofluorescence assay and electron microscopy. Phylogenetic analysis of a partial (804 nt) viral glycoprotein gC gene sequence indicated that it was likely to be a field strain closely related to a cluster of PRV previously identified in China.

A natural reassortant and mutant serotype 3 reovirus from mink in China.

Mammalian orthoreoviruses (MRVs) are widespread and infect virtually all mammals. We report here the first case of a natural mutant and reassortant serotype 3 reovirus from mink in China, known as MRV3 SD-14. Whole-genome sequence analysis showed that the MRV3 SD-14 may have resulted from a reassortment involving MRVs that infected swine, humans and mink. Interestingly, the S1 segment, which encodes the viral attachment protein σ1, which influences viral virulence and cell tropism in the host, had a stop codon mutation at amino acid 246. Surveillance of the virulence and evolution of MRVs in humans and other animals deserves more attention.