Genotype of dengue virus serotype 1 in relation to severe dengue in Guangzhou, China.

Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV-1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV-1 genotypes and SD. To understand the association between DENV-1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV-1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV-1 genotype. In the case of DENV-1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN-γ, TNF-α, IL-10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T-cell expressed and secreted and growth-related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV-1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.

Majorana Zero Modes Induced by the Meissner Effect at Small Magnetic Field.

One key difficulty in realizing Majorana zero modes (MZMs) is the required high magnetic field, which causes serious issues, e.g., shrinks the superconducting gap, reduces topological region, and weakens their robustness against disorders. In this Letter, we propose that the Meissner effect can bring the topological superconducting phase to a superconductor/topological-insulator/superconductor (SC/TI/SC) hybrid system. Remarkably, the required magnetic field strength (<10 mT) to support MZMs has been reduced by several orders of magnitude compared to that (>0.5 T) in the previous schemes. Tuning the phase difference between the top and bottom superconductors can control the number and position of the MZMs. In addition, we account for the electrostatic potential in the superconductor/topological-insulator (SC/TI) interface through the self-consistent Schrödinger-Poisson calculation, which shows the experimental accessibility of our proposal. Our proposal only needs a small magnetic field of less than 10 mT and is robust against the chemical potential fluctuation, which makes the SC/TI/SC hybrid an ideal Majorana platform.

Robust topological superconductivity in spin-orbit coupled systems at higher-order van Hove filling.

Van Hove singularities in proximity to the Fermi level promote electronic interactions and generate diverse competing instabilities. It is also known that a nontrivial Berry phase derived from spin-orbit coupling can introduce an intriguing decoration into the interactions and thus alter correlated phenomena. However, it is unclear how and what type of new physics can emerge in a system featured by the interplay between van Hove singularities (VHSs) and the Berry phase. Here, based on a general Rashba model on the square lattice, we comprehensively explore such an interplay and its significant influence on the competing electronic instabilities by performing a parquet renormalization group analysis. Despite the existence of a variety of comparable fluctuations in the particle-particle and particle-hole channels associated with higher-order VHSs, we find that the chiral p±ip pairings emerge as two stable fixed trajectories within the generic interaction parameter space, namely the system becomes a robust topological superconductor. The chiral pairings stem from the hopping interaction induced by the nontrivial Berry phase. The possible experimental realization and implications are discussed. Our work sheds new light on the correlated states in quantum materials with strong spin-orbit coupling (SOC) and offers fresh insights into the exploration of topological superconductivity.

Tuning interfacial two-component superconductivity in CoSi2/TiSi2 heterojunctions via TiSi2 diffusivity.

We report the observation of enhanced interfacial two-component superconductivity possessing a dominant triplet component in nonmagnetic CoSi2/TiSi2 superconductor/normal-metal planar heterojunctions. This is accomplished through the detection of odd-frequency spin-triplet even-parity Cooper pairs in the diffusive normal-metal component of T-shaped proximity junctions. We show that by modifying the diffusivity of the normal-metal part, the transition temperature enhancement can be tuned by a factor of up to 2.3 while the upper critical field increases by up to a factor of 20. Our data suggest that the C49 phase of TiSi2, which is stabilized in confined geometries, underlies this enhancement. These findings are addressed via a Ginzburg-Landau model and the quasi-classical theory. We also relate our findings to the enigmatic 3-K phase reported in Sr2 RuO4.

Controlling Dzyaloshinskii-Moriya interaction in a centrosymmetric nonsymmorphic crystal.

Presence of the Dzyaloshinskii-Moriya (DM) interaction in limited noncentrosymmetric materials leads to novel spin textures and exotic chiral physics. The emergence of DM interaction in centrosymmetric crystals could greatly enrich material realization. Here we show that an itinerant centrosymmetric crystal respecting a nonsymmorphic space group is a new platform for the DM interaction. Taking the P4/nmm space group as an example, we demonstrate that the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction induces the DM interactions, in addition to the Heisenberg exchange and the Kaplan-Shekhtman-Entin-wohlman-Aharony (KSEA) interaction. The direction of DM vector depends on the positions of magnetic atoms in the real space, and the amplitude depends on the location of the Fermi surface in the reciprocal space. The diversity stems from the position-dependent site groups and the momentum-dependent electronic structures guaranteed by the nonsymmorphic symmetries. Our study unveils the role of the nonsymmorphic symmetries in affecting magnetism, and suggests that the nonsymmorphic crystals can be promising platforms to design magnetic interactions.

Prevalence and correlates of elder neglect in the community-dwelling Chinese population: New evidence from the CLHLS study.

Background: This study aimed to explore the prevalence of elder neglect (EN) and its associated factors among community-based Chinese older adults. Methods: We used data from the 2018 phase of a nationwide cross-sectional study, the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which recruited 15,854 older adults to complete the study interviews that incorporated six dimensions of EN, namely, life neglect, social isolation, medical neglect, poor living situation, family neglect, and social neglect. Multivariate logistic regression was used to explore factors associated with EN. Results: We included demographic factors, chronic diseases, cognitive function, and daily activity function in our comprehensive analysis and showed that they had different effects on the six EN dimensions. Different demographic factors such as gender, age, marriage, education, occupation, residence, and household income were included in the comprehensive analysis, and the results showed that these factors had different effects on the six dimensions of EN. Next, we found that older adults with chronic diseases are prone to life neglect, medical neglect, and residential environment neglect. Older adults with better cognitive abilities were less likely to be neglected, and a decline in daily activity capacity has been linked to EN in older adults. Conclusion: Future studies are needed to identify the health effects of these associated factors, develop prevention strategies for EN, and improve the quality of life of older adults living in communities.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Controllable Majorana vortex states in iron-based superconducting nanowires.

To reveal the non-Abelian braiding statistics of Majorana zero modes (MZMs), it is crucial to design a Majorana platform, in which MZMs can be easily manipulated in a broad topological nontrivial parameter space. This is also an essential step to confirm their existence. In this study, we propose an iron-based superconducting nanowire system with Majorana vortex states to satisfy desirable conditions. This system has a radius-induced topological phase transition, giving a lower bound for the nanowire radius. In the topological phase, the iron-based superconducting nanowires have only one pair of MZMs over a wide range of radii, chemical potential and external magnetic fields. The wave function of MZMs has a sizable distribution at the side edge of the nanowires. This property enables the control of the interaction of MZMs in neighboring vortex nanowires and paves the way for Majorana fusion and braiding.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Observation of triplet superconductivity in CoSi2/TiSi2 heterostructures.

Unconventional superconductivity and, in particular, triplet superconductivity have been front and center of topological materials and quantum technology research. Here, we report our observation of triplet pairing in nonmagnetic CoSi2/TiSi2 heterostructures on silicon. CoSi2 undergoes a sharp superconducting transition at a critical temperature T c ≃ 1.5 K, while TiSi2 is a normal metal. We investigate conductance spectra of both two-terminal CoSi2/TiSi2 contact junctions and three-terminal T-shaped CoSi2/TiSi2 superconducting proximity structures. Below T c, we observe (i) a narrow zero-bias conductance peak on top of a broad hump, accompanied by two symmetric side dips in the contact junctions, (ii) a narrow zero-bias conductance peak in T-shaped structures, and (iii) hysteresis in the junction magnetoresistance. These three independent and complementary observations point to chiral p-wave pairing in CoSi2/TiSi2 heterostructures. The excellent fabrication compatibility of CoSi2 and TiSi2 with present-day silicon-based integrated-circuit technology suggests their potential use in scalable quantum-computing devices.

In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection.

Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein-Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens.

A Raman probe of phonons and electron-phonon interactions in the Weyl semimetal NbIrTe4.

There is tremendous interest in measuring the strong electron-phonon interactions seen in topological Weyl semimetals. The semimetal NbIrTe4 has been proposed to be a Type-II Weyl semimetal with 8 pairs of opposite Chirality Weyl nodes which are very close to the Fermi energy. We show using polarized angular-resolved micro-Raman scattering at two excitation energies that we can extract the phonon mode dependence of the Raman tensor elements from the shape of the scattering efficiency versus angle. This van der Waals semimetal with broken inversion symmetry and 24 atoms per unit cell has 69 possible phonon modes of which we measure 19 modes with frequencies and symmetries consistent with Density Functional Theory calculations. We show that these tensor elements vary substantially in a small energy range which reflects a strong variation of the electron-phonon coupling for these modes.

Universal Behavior of the Thermal Hall Conductivity.

We report theoretical and experimental analyses of the thermal Hall conductivity in correlated systems. For both fermionic and bosonic excitations with nontrivial topology, we show that at "intermediate" temperatures, the thermal Hall conductivity exhibits an unexpected universal scaling with a simple exponential form. At low temperatures, it behaves differently and reflects the spectral properties of underlying excitations. Our predictions are examined as examples in two prototype compounds, the quantum paraelectric SrTiO_{3} and the spin-liquid compound RuCl_{3}. The experimental data can be largely covered by our proposed minimal phenomenological model independent of microscopic details, revealing dominant bosonic contributions in SrTiO_{3} and gapped fermionic excitations in RuCl_{3}. Our work establishes a phenomenological link between microscopic models and experimental data and provides a unified basis for analyzing the thermal Hall conductivity in correlated systems over a wide temperature region.

Novel pathogenic characteristics of highly pathogenic avian influenza virus H7N9: viraemia and extrapulmonary infection.

The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.

Scalable Majorana vortex modes in iron-based superconductors.

The iron-based superconductor FeTe x Se1-x is one of the material candidates hosting Majorana vortex modes residing in the vortex cores. It has been observed by recent scanning tunneling spectroscopy measurement that the fraction of vortex cores having zero-bias peaks decreases with increasing magnetic field on the surface of FeTe x Se1-x . The hybridization of two Majorana vortex modes cannot simply explain this phenomenon. We construct a three-dimensional tight-binding model simulating the physics of over a hundred Majorana vortex modes in FeTe x Se1-x . Our simulation shows that the Majorana hybridization and disordered vortex distribution can explain the decreasing fraction of the zero-bias peaks observed in the experiment; the statistics of the energy peaks off zero energy in our Majorana simulation are in agreement with the experiment. These agreements lead to an important indication of scalable Majorana vortex modes in FeTe x Se1-x . Thus, FeTe x Se1-x can be one promising platform having scalable Majorana qubits for quantum computing.

Defervescent dengue patients might be a potential source of infection for vector mosquitoes.

BACKGROUND: Dengue is a re-emerging public health problem and mosquito-borne infectious disease that is transmitted mainly by Aedes aegypti and Ae. albopictus. Early diagnosis, isolation, and treatment of patients are critical steps for dengue epidemic control, especially to prevent secondary transmission of dengue virus (DENV). However, little is known about defervescent dengue patients as a source of infection. METHODS: This case study describes 1268 dengue patients hospitalized at Guangzhou Eighth People's Hospital from June 2013 to December 2014. The viral loads of each individual were measured using real-time reverse transcription-polymerase chain reaction. Ae. aegypti and Ae. albopictus were exposed to blood meal with gradated dengue viral loads to characterize the relationship between viremia in dengue patients and the vector competence of vector mosquitoes. RESULTS: The viral numbers in the blood were measured, ranging from 108 to 103 copies/ml from day 1 to day 12 after fever onset. Vector competence analysis of Ae. aegypti and Ae. albopictus indicated that viremia > 104 copies/ml can still infect vector mosquitoes, which implied that the defervescent dengue patients might be a source of infection. CONCLUSIONS: The results of this study indicate that some defervescent dengue patients still have sufficient viral load to infect vector mosquitoes. Therefore, the protection against mosquito biting for these people should be extended to prevent secondary transmission events.

The clinical significance of myeloid-derived suppressor cells in dengue fever patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.

Quasi-1D Topological Nodal Vortex Line Phase in Doped Superconducting 3D Dirac Semimetals.

We study vortex bound states in three-dimensional (3D) superconducting Dirac semimetals with time reversal symmetry. We find that there exist robust gapless vortex bound states propagating along the vortex line in the s-wave superconducting state. We refer to this newly found phase as the quasi-1D nodal vortex line phase. According to the Altland-Zirnbauer classification, the phase is characterized by a topological index (ν;N) at k_{z}=0 and k_{z}=π, where ν is the Z_{2} topological invariant for a 0D class-D system and N is the Z topological invariant for a 0D class-A system. Furthermore, we show that the vortex end Majorana zero mode can coexist with the quasi-1D nodal phase in certain types of Dirac semimetals. The possible experimental observations and material realization of such nodal vortex line states are discussed.

Zika Virus Infection in Tupaia belangeri Causes Dermatological Manifestations and Confers Protection against Secondary Infection.

Animal models of Zika virus (ZIKV) infection have recently been established in mice, guinea pigs, and nonhuman primates. Tree shrews (Tupaia belangeri) are an emerging experimental animal in biomedical applications, but their susceptibility to ZIKV infection has not been explored. In the present study, we show that subcutaneous inoculation of ZIKV led to rapid viremia and viral secretion in saliva, as well as to typical dermatological manifestations characterized by massive diffuse skin rash on the trunk. Global transcriptomic sequencing of peripheral blood mononuclear cells isolated from ZIKV-infected animals revealed systematic gene expression changes related to the inflammatory response and dermatological manifestations. Importantly, ZIKV infection readily triggered the production of high-titer neutralizing antibodies, thus preventing secondary homologous infection in tree shrews. However, neonatal tree shrews succumbed to ZIKV challenge upon intracerebral infection. The tree shrew model described here recapitulates the most common dermatological manifestations observed in ZIKV-infected patients and may greatly facilitate the elucidation of ZIKV pathogenesis and the development of novel vaccines and therapeutics.IMPORTANCE The reemergence of Zika virus (ZIKV) has caused a global public health crisis since 2016, and there are currently no vaccines or antiviral drugs to prevent or treat ZIKV infection. However, considerable advances have been made in understanding the biology and pathogenesis of ZIKV infection. In particular, various animal models have been successfully established to mimic ZIKV infection and its associated neurological diseases and to evaluate potential countermeasures. However, the clinical symptoms in these mouse and nonhuman primate models are different from the common clinical manifestations seen in human ZIKV patients; in particular, dermatological manifestations are rarely recapitulated in these animal models. Here, we developed a new animal model of ZIKV infection in tree shrews, a rat-sized, primate-related mammal. In vitro and in vivo characterization of ZIKV infection in tree shrews established a direct link between ZIKV infection and the immune responses and dermatological manifestations. The tree shrew model described here, as well as other available animal models, provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccines and therapeutics.