In Cooper pairs--pairs of electrons responsible for the exotic properties of superconductors--the two electrons' spins typically point in opposite directions. A strong-enough external magnetic field ...will destroy superconductivity by making the spins point in the same direction. Lu et al. observed a two-dimensional superconducting state in the material MoS2 that was surprisingly immune to a magnetic field applied in the plane of the sample (see the Perspective by Suderow). The band structure of MoS2 and its spin-orbit coupling conspired to create an effective magnetic field that reinforced the electron pairing, with spins aligned perpendicular to the sample. Science, this issue p. 1353; see also p. 1316 The Zeeman effect, which is usually detrimental to superconductivity, can be strongly protective when an effective Zeeman field from intrinsic spin-orbit coupling locks the spins of Cooper pairs in a direction orthogonal to an external magnetic field. We performed magnetotransport experiments with ionic-gated molybdenum disulfide transistors, in which gating prepared individual superconducting states with different carrier dopings, and measured an in-plane critical field Bc2 far beyond the Pauli paramagnetic limit, consistent with Zeeman-protected superconductivity. The gating-enhanced Bc2 is more than an order of magnitude larger than it is in the bulk superconducting phases, where the effective Zeeman field is weakened by interlayer coupling. Our study provides experimental evidence of an Ising superconductor, in which spins of the pairing electrons are strongly pinned by an effective Zeeman field.
Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for ...Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health
. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics
. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
Summary
In this study, we aimed at investigating the impact of melatonin supplementation on semen parameters, hormonal profile and total antioxidant capacity after varicocelectomy. Infertile male ...patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 27 receiving melatonin for 3 months and 27 as the placebo‐controlled group receiving placebo for 3 months. The pre‐operative parameters of semen analyses, hormonal profile and seminal oxidative stress status of both groups were compared with those of post‐operative parameters. There were statistically significant improvements in post‐operative parameters of semen analyses (sperm concentration, motility and proportions of normally formed spermatozoa), peripheral blood inhibin B and total antioxidant capacity in melatonin group compared with placebo group. In conclusion, melatonin therapy adds extra benefit to varicecelectomy in terms of sperm parameters, peripheral blood inhibin B and total antioxidant capacity; however, further studies including large number of samples are needed to make a proper decision on melatonin supplementation after varicocelectomy.
MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large ...number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molecular mechanism of miR-330 in determining the aggressiveness of human prostate cancer has not been studied. Here, we show that miR-330 is significantly lower expressed in human prostate cancer cell lines than in nontumorigenic prostate epithelial cells. Bioinformatics analyses reveal a conserved target site for miR-330 in the 3'-untranslated region (UTR) of E2F1 at nucleotides 1018-1024. MiR-330 significantly suppressed the activity of a luciferase reporter containing the E2F1-3'-UTR in the cells. This activity could be abolished with the transfection of anti-miR-330 or mutated E2F1-3'-UTR. In addition, the expression level of miR-330 and E2F1 was inversely correlated in cell lines and prostate cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing apoptosis. Collectively, this is the first study to show that E2F1 is negatively regulated by miR-330 and also show that miR-330 induces apoptosis in prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation.
Summary
Background
Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD).
Objectives
To evaluate the efficacy and safety of dupilumab in adult ...Chinese patients with moderate‐to‐severe AD.
Methods
In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator’s Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16.
Results
Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group.
Conclusions
In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.
What is already known about this topic?
Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.
However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear.
What does this study add?
The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population.
Plain language summary available online
We have earlier shown that antisense morpholino oligomers are able to restore dystrophin expression by systemic delivery in body-wide skeletal muscles of dystrophic mdx mice. However, the levels of ...dystrophin expression vary considerably and, more importantly, no dystrophin expression has been achieved in cardiac muscle. In this study, we investigate the efficiency of morpholino-induced exon skipping in cardiomyoblasts and myocytes in vitro, and in cardiac muscle in vivo by dose escalation. We showed that morpholino induces targeted exon skipping equally effectively in both skeletal muscle myoblasts and cardiomyoblasts. Effective exon skipping was achieved in cardiomyocytes in culture. In the mdx mice, morpholino rescues dystrophin expression dose dependently in both skeletal and cardiac muscles. Therapeutic levels of dystrophin were achieved in cardiac muscle albeit at higher doses than in skeletal muscles. Up to 50 and 30% normal levels of dystrophin were induced by single systemic delivery of 3 g kg(-1) of morpholino in skeletal and cardiac muscles, respectively. High doses of morpholino treatment reduced the serum levels of creatine kinase without clear toxicity. These findings suggest that effective rescue of dystrophin in cardiac muscles can be achieved by morpholino for the treatment of Duchenne muscular dystrophy.
Understanding the microscopic origins of electronic phases in high-transition temperature (high-Tc) superconductors is important for elucidating the mechanism of superconductivity. In the ...paramagnetic tetragonal phase of BaFe2–xTxAs2 (where T is Co or Ni) iron pnictides, an in-plane resistivity anisotropy has been observed. Here, we use inelastic neutron scattering to show that low-energy spin excitations in these materials change from fourfold symmetric to twofold symmetric at temperatures corresponding to the onset of the in-plane resistivity anisotropy. Because resistivity and spin excitation anisotropies both vanish near optimal superconductivity, we conclude that they are likely intimately connected.
Hydrogen energy-based electrochemical energy conversion technologies offer the promise of enabling a transition of the global energy landscape from fossil fuels to renewable energy. Here, we present ...a comprehensive review of the fundamentals of electrocatalysis in alkaline media and applications in alkaline-based energy technologies, particularly alkaline fuel cells and water electrolyzers. Anion exchange (alkaline) membrane fuel cells (AEMFCs) enable the use of nonprecious electrocatalysts for the sluggish oxygen reduction reaction (ORR), relative to proton exchange membrane fuel cells (PEMFCs), which require Pt-based electrocatalysts. However, the hydrogen oxidation reaction (HOR) kinetics is significantly slower in alkaline media than in acidic media. Understanding these phenomena requires applying theoretical and experimental methods to unravel molecular-level thermodynamics and kinetics of hydrogen and oxygen electrocatalysis and, particularly, the proton-coupled electron transfer (PCET) process that takes place in a proton-deficient alkaline media. Extensive electrochemical and spectroscopic studies, on single-crystal Pt and metal oxides, have contributed to the development of activity descriptors, as well as the identification of the nature of active sites, and the rate-determining steps of the HOR and ORR. Among these, the structure and reactivity of interfacial water serve as key potential and pH-dependent kinetic factors that are helping elucidate the origins of the HOR and ORR activity differences in acids and bases. Additionally, deliberately modulating and controlling catalyst–support interactions have provided valuable insights for enhancing catalyst accessibility and durability during operation. The design and synthesis of highly conductive and durable alkaline membranes/ionomers have enabled AEMFCs to reach initial performance metrics equal to or higher than those of PEMFCs. We emphasize the importance of using membrane electrode assemblies (MEAs) to integrate the often separately pursued/optimized electrocatalyst/support and membranes/ionomer components. Operando/in situ methods, at multiscales, and ab initio simulations provide a mechanistic understanding of electron, ion, and mass transport at catalyst/ionomer/membrane interfaces and the necessary guidance to achieve fuel cell operation in air over thousands of hours. We hope that this Review will serve as a roadmap for advancing the scientific understanding of the fundamental factors governing electrochemical energy conversion in alkaline media with the ultimate goal of achieving ultralow Pt or precious-metal-free high-performance and durable alkaline fuel cells and related technologies.