Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in Proteus mirabilis isolated from China, 2018-2020.

Proteus mirabilis can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of P. mirabilis were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive P. mirabilis exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to Escherichia coli EC600 with a frequency of 2.0 × 10-7 to 6.0 × 10-5. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICEPmiChnHBRJC2 carries erm (42), which have never been found within an SXT/R391 ICE in P. mirabilis, and ICEPmiChnSC1111 carries 19 ARGs, including clinically important cfr, blaCTX-M-65, and aac(6')-Ib-cr, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICEPmiChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICEPmiChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in P. mirabilis.IMPORTANCEThe spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in Proteus mirabilis, which can transfer ARGs to other hosts. The study found that all of the P. mirabilis strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.

Visible-light-induced [3+2] cycloadditions of donor/donor diazo intermediates with alkenes to achieve (spiro)-pyrazolines and pyrazoles.

To date, [3 + 2] cycloadditions of diazo esters with alkynes or alkenes have been a robust tool to generate pyrazoles and pyrazolines. However, methods capable of generating donor/donor diazo species from readily available N-tosylhydrazones to furnish [3 + 2] cycloadditions, remain elusive. Herein, we describe the first visible-light-induced [3 + 2] cycloadditions of donor/donor diazo precursors with alkenes to afford pyrazoles and novel (spiro)pyrazolines bearing a quaternary center. This protocol shows a tolerable substrate scope covering versatile carbonyl compounds and alkenes. Late-stage functionalization of bioactive molecules, one-pot approach, and gram-scale synthesis have also been introduced successfully to prove the practicability. At last, mechanistic experiments and DFT studies suggested the formation of non-covalent interactions enabling the activation of N-tosylhydrazones and the formation of the donor/donor diazo intermediates.

[Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

[Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Two Novel Species of Mesophoma gen. nov. from China.

During an investigation of the fungal pathogens associated with the invasive weed Ageratina adenophora from China, some interesting isolates were obtained from healthy leaf, leaf spot, and roots of this weed. Among them, a novel genus Mesophoma, containing two novel species M. speciosa and M. ageratinae, was found. Phylogenetic analysis of the combined, the internal transcribed spacer (ITS), large nuclear subunit ribosomal DNA (LSU), the RNA polymerase II second largest subunit (rpb2), and the partial ß-tubulin (tub2) sequences, showed that M. speciosa and M. ageratinae formed a distinct clade far from all genera previously described in the family Didymellaceae. Combined distinctive morphological characters, including smaller and aseptate conidia when comparing with nearby genera Stagonosporopsis, Boeremia, and Heterphoma, allowed us to describe them as novel species belonging to a novel genus Mesophoma. The full descriptions, illustrations, and a phylogenetic tree showing the position of both M. speciosa and M. ageratinae are provided in this paper. Moreover, the potential for two strains belonging to these two species to be developed into a biocontrol for the spread of the invasive weed Ag. adenophora is also discussed.

Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone.

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.

Heralded Nondestructive Quantum Entangling Gate with Single-Photon Sources.

Heralded entangling quantum gates are an essential element for the implementation of large-scale optical quantum computation. Yet, the experimental demonstration of genuine heralded entangling gates with free-flying output photons in linear optical system, was hindered by the intrinsically probabilistic source and double-pair emission in parametric down-conversion. Here, by using an on-demand single-photon source based on a semiconductor quantum dot embedded in a micropillar cavity, we demonstrate a heralded controlled-NOT (CNOT) operation between two single photons for the first time. To characterize the performance of the CNOT gate, we estimate its average quantum gate fidelity of (87.8±1.2)%. As an application, we generated event-ready Bell states with a fidelity of (83.4±2.4)%. Our results are an important step towards the development of photon-photon quantum logic gates.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Proof-of-principle demonstration of compiled Shor's algorithm using a quantum dot single-photon source.

We report a proof-of-principle demonstration of Shor's algorithm with photons generated by an on-demand semiconductor quantum dot single-photon source for the first time. A fully compiled version of Shor's algorithm for factoring 15 has been accomplished with a significantly reduced resource requirement that employs the four-photon cluster state. Genuine multiparticle entanglement properties are confirmed to reveal the quantum character of the algorithm and circuit. The implementation realizes the Shor's algorithm with deterministic photonic qubits, which opens new applications for cluster state beyond one-way quantum computing.

Quantum Interference between Light Sources Separated by 150 Million Kilometers.

We report an experiment to test quantum interference, entanglement, and nonlocality using two dissimilar photon sources, the Sun and a semiconductor quantum dot on the Earth, which are separated by ∼150 million kilometers. By making the otherwise vastly distinct photons indistinguishable in all degrees of freedom, we observe time-resolved two-photon quantum interference with a raw visibility of 0.796(17), well above the 0.5 classical limit, providing unambiguous evidence of the quantum nature of thermal light. Further, using the photons with no common history, we demonstrate postselected two-photon entanglement with a state fidelity of 0.826(24) and a violation of Bell inequality by 2.20(6). The experiment can be further extended to a larger scale using photons from distant stars and open a new route to quantum optics experiments at an astronomical scale.

Piezoelectric and polarized enhancement by hydrofluorination of penta-graphene.

Motivated by the challenges in the harnessing of energy and the continuing trend of miniaturizing devices, an exhaustive evaluation of the electronic, mechanical and piezoelectric properties of surface modified penta-graphene (PG), including fluorinated PG (F-PG-F), hydrofluorinated PG (H-PG-F) and hydrogenated PG (H-PG-H), was carried out via a first-principles approach based on density functional theory. We first predicted the H-PG-F system and calculated its phonon dispersion and magnetic properties. All three systems were found to exhibit an e31 piezoelectric effect, and the e31 (96.88 pC m-1) effect of H-PG-F was found to be much greater than that of the other two systems. So, it could be concluded that hydrofluorination can significantly enhance the piezoelectric properties of PG. The binding energy and formation energy of the H-PG-F system were found to be the lowest among the three surface modified PG systems, showing that the H-PG-F system is the most energetically favorable state. The e31 piezoelectricity can be potentially engineered into a PG monolayer by surface modification, providing an avenue for monolithic integration of electronic and electromechanical devices with a PG monolayer for use in mechanical stress-sensors, nano-sized actuators and energy harvesting systems. The H-PG-F system stands out in terms of its combination of a larger piezoelectric coefficient (e31 = 96.88 pC m-1), negative Poisson's ratio and low formation energy (-3.37 eV) and is recommended for experimental exploration.

Two N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicarboxamide coordination compounds.

The molecular structures of tetra-aqua-[N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicar-boxamide]-sulfatomanganese(II) dihydrate, [Mn(SO4)(C17H13N5O2)(H2O)4]·2H2O or [Mn(H2L1)(SO4)(H2O)4]·2H2O, (I), and tetra-aqua-bis[N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicar-boxamide]cadmium(II) sulfate tetra-hydrate, [Cd(C17H13N5O2)2(H2O)4]SO4·4H2O or [Cd(H2O)4(H2L1)2]·SO4·4H2O, (II), both contain a central metal atom in a distorted octa-hedral geometry coordinated equatorially by four oxygen atoms from water mol-ecules. In (I), the axial positions are occupied by a nitro-gen atom from H2L1 and an oxygen atom from the sulfate anion, whereas in (II), the axial positions contain two nitro-gen atoms from two different H2L1 ligands and the sulfate anion acts as the charge-balancing ion. π-π stacking between pyridine rings and a network of hydrogen bonds involving the water molecules and the sulfate anions play a crucial role in the mol-ecular self-assembly of the two structures.

[Effects of cascading hydropower dams operation on the structure and distribution pattern of benthic macroinvertebrate assemblages in Manwan Reservoir, Southwest China]. / æ¢¯çº§æ°´åè¿è¡Œå¯¹æ¼«æ¹¾åº“åŒºåº•æ –åŠ¨ç‰©ç¾¤è½ç»“æž„åŠåˆ†å¸ƒæ ¼å±€çš„å½±å“.

Benthic macroinvertebrate assemblages are one of the biological groups in aquatic ecosystem most sensitive to the habitat change and degradation, and can be a biological indicator for the aquatic ecosystem change and succession in cascading hydropower dam reservoir. The middle and lower reaches of the Lancang River are key spot for international biodiversity conservation and ecological studies on the effects of cascading hydropower dam exploitation. In this study, the reservoir of Manwan hydropower dam, the first dam in Lancang-Mekong river main stream, was selected as the study site. The benthic macroinvertebrate assemblages were sampled in 2011 and 2016 respectively. Meanwhile, the survey data before impounding (natural river, 1996) and early stage of single dam (1997) were collected to conduct the overall analysis for structure, distribution pattern and evolution of benthic macroinvertebrate assemblages. The results showed that the dominant biological group was gradually changed from the Oligochaeta and Insecta to the Mollusca. Along the longitudinal gradient, the density and biomass of the benthic macroinvertebrate assemblages were remarkably increased in reservoir, especially in the lacustrine zone. As for the functional feeding group, the predator and gatherer-collector changed into filter-collector predominantly in lacustrine zone. With the cascading dams operation, the biotic index indicated that the water quality of reservoir in 2016 was better than in 2011. The evolution of benthic macroinvertebrate assemblages in the Manwan Reservoir was related to the operation of Xiaowan dam in the upper reach, the hydrological regime and siltation in the reservoir, and would continue with dynamic changes with the operation of the cascading hydropower dam.

miR-146a G>C polymorphisms and risk of hepatocellular carcinoma in a Chinese population.

MicroRNAs (miRNAs) are thought to have a role in cancer development. We investigated the association among miR-146a G>C genetic variations, hepatitis B (HBV), and C (HCV) infection, and risk of hepatocellular carcinoma (HCC). Unconditional logistical regression analysis suggested that the miR-146a GG genotype and G allele carried a 2.10- (95 % confidence interval (CI)=1.03-4.37) and 1.42-fold (95 % CI=1.07-1.92) increased HCC risk, respectively. HBV-positive subjects carrying the miR-146a GG genotype (odds ratio (OR)=2.95, 95 % CI=1.31-6.81) and G allele (OR=1.65, 95 % CI=1.15-2.58) had an increased risk of HCC. However, the miR-146a GG genotype and G allele did not carry a significantly enhanced risk of HCC in either hepatitis-negative or HCV-infected subjects. miR-146a G>C polymorphisms appear to influence susceptibility to HCC, especially in HBV-infected patients.

[Ecological risk assessment of hydropower dam construction on aquatic species in middle reaches of Lancang River, Southwest China based on ESHIPPO model].

An investigation was conducted on the phytoplankton, zooplankton, and fish at 8 sampling sections in the Manwan Reservoir before and after the construction of Xiaowan Hydropower Dam. The modified ESHIPPO model was applied to study the changes of the featured aquatic species, including endangered species, endemic specie, peis resource species, and native fish, aimed to make an ecological risk assessment of the dam construction on the aquatic species. The dam construction had definite ecological risk on the aquatic species, especially the endemic fish, in Langcang River, due to the changes of hydrological conditions. The endemic species including Bangia atropurpurea, Lemanea sinica, Prasiola sp., Attheyella yunnanensis, and Neutrodiaptomus mariadvigae were at high ecological risk, and thus, besides monitoring, protection measures were needed to be taken to lower the possibility of the species extinction. The widely distributed species of phytoplankton and zooplankton were at medium ecological risk, and protection measures besides monitoring should be prepared. Twelve kinds of native fish, including Barbodes huangchuchieni, Sinilabeo laticeps, Racoma lantsangensis, Racoma lissolabiatus, Paracobitis anguillioides, Schistura latifasciata, Botia nigrolineata, Vanmanenia striata, Homaloptera yunnanensis, Platytropius longianlis, Glyptothorax zanaensis, and Pseudecheneis immaculate, were at high ecological risk, and protection measures needed to be developed to prevent the possibility of the species loss and extinction.

[Ecological risk assessment of dam construction for terrestrial plant species in middle reach of Lancangjiang River, Southwest China].

Taking the surrounding areas of Xiaowan Reservoir in the middle reach of Lancangjiang River as study area, and based on the vegetation investigation at three sites including electricity transmission area (site 1), electricity-transfer substation and roadsides to the substation (site 2), and emigration area (site 3) in 1997 (before dam construction), another investigation was conducted on the vegetation composition, plant coverage, and dominant species at the same sites in 2010 (after dam construction), aimed to evaluate the ecological risk of the dam construction for the terrestrial plant species in middle reach of Lancangjiang River. There was an obvious difference in the summed dominance ratio of dominant species at the three sites before and after the dam construction. According the types of species (dominant and non-dominant species) and the changes of plant dominance, the ecological risk (ER) for the plant species was categorized into 0 to IV, i.e., no or extremely low ecological risk (0), low ecological risk (I), medium ecological risk (II), high ecological risk (III), and extremely high ecological risk (IV). As affected by the dam construction, the majority of the species were at ER III, and a few species were at ER IV. The percentage of the plant species at ER III and ER IV at site 3 was higher than that at sites 1 and 2. The decrease or loss of native plants and the increase of alien or invasive plants were the major ecological risks caused by the dam construction. Effective protection strategies should be adopted to mitigate the ecological risk of the dam construction for the terrestrial plants at species level.

Synergistic effect of IFN-γ gene on LIGHT-induced apoptosis in HepG2 cells via down regulation of Bcl-2.

To detect the expression of anti-apoptotic factor Bcl-2 and Survivin in transferred HepG2 cells and evaluate the synergistic effect of IFN-γ gene on LIGHT-induced apoptosis signal transduction pathways, the full-length ORF of LIGHT and IFN-γ gene were cloned into pcDNA4 and verified by DNA sequencing. After being optimized by EGFP, recombinant LIGHT and IFN-γ were transferred into the HepG2 cells mediated by a cationic liposome in vitro. The expression of LIGHT and IFN-γ was identified in the supernatants by ELISA. The HepG2 cells were divided into three groups: the control, LIGHT gene transfection alone, and simultaneous transfection of LIGHT and IFN-γ genes. The cell apoptosis and expression of Bcl-2 and Survivin in cell lysate were detected through FCM. After transfection, the apoptosis rate of HepG2 cells was increased with the prolonged time, and the apoptosis rate of LIGHT group was higher than the control group, while the LIGHT/IFN-γ group was higher than the LIGHT group P < 0.01). The expression of Bcl-2 and Survivin in LIGHT group and LIGHT/IFN-γ group decreased dramatically compared with the control group. LIGHT gene alone can result in significant inhibition of HepG2 cells proliferation. INF-γ can synergistically precede LIGHT-induced apoptotic processes through down-regulation of Bcl-2 expression, but not survivin expression.

Synthesis, properties, and theoretical studies of new stepwise layered iodoplumbate: [Ni(opd)2(acn)2]n[Pb4I10]n.

A novel 2D layered iodoplumbate, [Ni(opd)(2)(acn)(2)](n)[Pb(4)I(10)](n) (1), yellow-green in color, has been synthesized. The anionic [Pb(4)I(10)(2-)](n) layer is comparable to the hexagonal PbI(2) sheet but in a lower symmetry. Although the intercalated cations contribute negligibly to the electron transition, they induce the reconstruction of the inorganic moiety, which leads to a band-gap blue shift with respect to that of PbI(2).