From imitation to innovation: A study of China's drug R&D and relevant national policies

Research & Development (R&D) plays an increasingly important role in China's pharmaceutical industry. To gain a competitive edge in the global pharmaceutical market, the current national strategy of China forcefully pushes for independent drug innovations. This article investigates the historical, legal, and institutional contexts in which China's drug R&D has evolved. Based on an analysis of the drug R&D evolution and national policies in China, it predicts the future trend of China's policies relevant to drug innovations. This paper helps to understand the impact of national policies on drug R&D in China, which can be used to inform decision-making on investments in China's pharmaceutical market or conducting technology trade and international cooperation with Chinese partners

Advances in bioorganic molecules inspired degradation and surface modifications on Mg and its alloys

Mg alloys possess biodegradability, suitable mechanical properties, and biocompatibility, which make them possible to be used as biodegradable implants. However, the uncontrollable degradation of Mg alloys limits their general applications. In addition to the factors from the metallic materials themselves, like alloy compositions, heat treatment process and microstructure, some external factors, relating to the test/service environment, also affect the degradation rate of Mg alloys, such as inorganic salts, bioorganic small molecules, bioorganic macromolecules. The influence of bioorganic molecules on Mg corrosion and its protection has attracted more and more attentions. In this work, the cutting-edge advances in the influence of bioorganic molecules (i.e., protein, glucose, amino acids, vitamins and polypeptide) and their coupling effect on Mg degradation and the formation of protection coatings were reviewed. The research orientations of biomedical Mg alloys in exploring degradation mechanisms in vitro were proposed, and the impact of bioorganic molecules on the protective approaches were also explored

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow failure is mediated by activated myeloid dendritic cells (mDCs) and T lymphocytes. Recent research has identified a strong immunomodulatory effect of pyruvate kinase M2 (PKM2) on dendritic cells in immune-mediated diseases. In this study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared to normal controls at both the gene and protein levels. Concurrently, we unexpectedly discovered that after the mDC-specific downregulation of PKM2, mDCs from patients with SAA exhibited weakened phagocytic activity and significantly decreased and shortened dendrites relative to their counterparts from normal controls. The expression levels of the costimulatory molecules CD86 and CD80 were also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs reduced the abilities of these cells to promote the activation of CD8+ T cells (CTLs), leading to the decreased secretion of cytotoxic factors by the latter cell type. These findings demonstrate that mDC activation requires an elevated intrinsic PKM2 level and that PKM2 improves the immune status of patients with SAA by enhancing the functions of mDCs and, consequently, CTLs

Plasmoid ejection and secondary current sheet generation from magnetic reconnection in laser-plasma interaction

Reconnection of the self-generated magnetic fields in laser-plasma interaction was first investigated experimentally by Nilson {\it et al.} [Phys. Rev. Lett. 97, 255001 (2006)] by shining two laser pulses a distance apart on a solid target layer. An elongated current sheet (CS) was observed in the plasma between the two laser spots. In order to more closely model magnetotail reconnection, here two side-by-side thin target layers, instead of a single one, are used. It is found that at one end of the elongated CS a fan-like electron outflow region including three well-collimated electron jets appears. The ($>1$ MeV) tail of the jet energy distribution exhibits a power-law scaling. The enhanced electron acceleration is attributed to the intense inductive electric field in the narrow electron dominated reconnection region, as well as additional acceleration as they are trapped inside the rapidly moving plasmoid formed in and ejected from the CS. The ejection also induces a secondary CS

Multidrug-resistant Pseudomonas aeruginosa is predisposed to lasR mutation through up-regulated activity of efflux pumps in non-cystic fibrosis bronchiectasis patients

BackgroundMultidrug-resistant (MDR) Pseudomonas aeruginosa is a frequent opportunistic pathogen that causes significant mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Although the quorum sensing (QS) system is a potential target for treatment, lasR mutants that present with a QS-deficient phenotype have been frequently reported among clinical P. aeruginosa isolates. We aimed to investigate whether antibiotic resistance would select for lasR mutants during chronic P. aeruginosa lung infection and determine the mechanism underlying the phenomenon.MethodsWe prospectively evaluated episodes of chronic P. aeruginosa lung infections in NCFB patients over a 2-year period at two centers of our institution. QS phenotypic assessments and whole-genome sequencing (WGS) of P. aeruginosa isolates were performed. Evolution experiments were conducted to confirm the emergence of lasR mutants in clinical MDR P. aeruginosa cultures.ResultsWe analyzed episodes of P. aeruginosa infection among 97 NCFB patients and found only prior carbapenem exposure independently predictive of the isolation of MDR P. aeruginosa strains. Compared with non-MDR isolates, MDR isolates presented significantly QS-deficient phenotypes, which could not be complemented by the exogenous addition of 3OC12-HSL. The paired isolates showed that their QS-phenotype deficiency occurred after MDR was developed. Whole-genome sequencing analysis revealed that lasR nonsynonymous mutations were significantly more frequent in MDR isolates, and positive correlations of mutation frequencies were observed between genes of lasR and negative-efflux-pump regulators (nalC and mexZ). The addition of the efflux pump inhibitor PAβN could not only promote QS phenotypes of these MDR isolates but also delay the early emergence of lasR mutants in evolution experiments.ConclusionsOur data indicated that MDR P. aeruginosa was predisposed to lasR mutation through the upregulated activity of efflux pumps. These findings suggest that anti-QS therapy combined with efflux pump inhibitors might be a potential strategy for NCFB patients in the challenge of MDR P. aeruginosa infections

Partial Wave Analysis of J/ψ→γ(K+K−π+π−)J/\psi \to \gamma (K^+K^-\pi^+\pi^-)

BES data on $J/\psi \to \gamma (K^+K^-\pi^+\pi^-)$ are presented. The $K^*\bar K^*$ contribution peaks strongly near threshold. It is fitted with a broad $0^{-+}$ resonance with mass $M = 1800 \pm 100$ MeV, width $\Gamma = 500 \pm 200$ MeV. A broad $2^{++}$ resonance peaking at 2020 MeV is also required with width $\sim 500$ MeV. There is further evidence for a $2^{-+}$ component peaking at 2.55 GeV. The non-$K^*\bar K^*$ contribution is close to phase space; it peaks at 2.6 GeV and is very different from $K^{*}\bar{K^{*}}$.Comment: 15 pages, 6 figures, 1 table, Submitted to PL

Study of the P-wave charmonium state \chi_{cJ} in \psi(2S) decays

The processes $\psi(2S)\to \gamma \pi^+ \pi^-$, $\gamma K^+ K^-$ and $\gamma p \bar{p}$ have been studied using a sample of $3.7 \times 10^6$ produced $\psi(2S)$ decays. We determine the total width of the $\chi_{c0}$ to be $\Gamma^{tot}_{\chi_{c0}} = 14.3\pm 2.0\pm 3.0$ MeV. We present the first measurement of the branching fraction $B(\chi_{c0} \to p \bar{p}) = (16.3 \pm 4.4 \pm 5.4)\times 10^{-5}$, where the first error is statistical and the second one systematic. Branching fractions of $\chi_{c0,2} \to \pi^+ \pi^-$ and $K^+ K^-$ are also reported.Comment: 10 pages, revtex, 3 figures, 2 table