“一带一路”沿线国家天然药物专利概况及“典型国家”专利分析

以除中国以外“一带一路”沿线64个国家及其中“典型国家”公开的天然药物专利数据为研究对象,分别从申请国排名、申请趋势、技术领域、药物制剂、治疗领域、地域布局等几个方面进行统计分析,为全面了解“一带一路”沿线国家天然药物专利概况及中医药企业在“一带一路”沿线国家进行专利布局提供参考。结果表明,“一带一路”沿线国家天然药物专利发展极其不平衡,其专利申请主要集中在俄罗斯、印度、印度尼西亚、乌克兰等少数国家;各国天然药物重点研发领域基本一致,主要集中在活性成分、制剂及化妆品领域;治疗用途重点在皮肤病、消化道疾病、感染及代谢相关疾病。印度、俄罗斯等国既是申请大国,也是对外布局最多的国家,同时还是世界其他国家进行天然药物申请的目标国。     

Functional parcellation of the human primary somatosensory cortex to natural touch

Despite the significance of human touch, brain responses to interpersonal manual touch have been rarely investigated. We used functional magnetic resonance imaging to study brain activity in eight healthy adults whose left hand was touched by two individuals, in separate runs and in 20‐s blocks, either by holding, smoothing, or poking. Acceleration was measured from both the subject's and the touching person's hands for postimaging control of the stimuli. Independent component analysis of the functional magnetic resonance imaging data unraveled three functional networks involving the primary somatosensory cortex (SI). One network comprised the contralateral and another the ipsilateral Brodmann area 3. The third network included area 2 bilaterally, left‐hemisphere middle temporal gyrus and dorsolateral prefrontal regions, ventral prefrontal cortices bilaterally, and middle cingulate cortex. The response shapes and polarities varied between the three networks. The contralateral area 3 differentiated the responses between the three types of touch stimuli, and the response magnitudes depended on the variability of the touch within each block. However, the responses of the other two networks were strikingly similar to all stimuli. The subjects' reports on the pleasantness of the touch did not correlate with the characteristics of the SI responses. These findings imply area‐specific processing of the natural human touch in three networks including the SI cortex, with only area 2 connected to a functional network of brain areas that may support social interaction.     

Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT

Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK–DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 [TNFSF14; also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT)], a cytokine implicated in the enhancement of antitumor responses. TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely, via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK-cell activation receptors, and by the cytokines IL-2 and IL-15. For antitumor responses, TNFSF14 was preferentially produced by the licensed NK-cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. In contrast, IL-2 and IL-15 treatment induced TNFSF14 production by both licensed and unlicensed NK cells, reflecting the ability of proinflammatory conditions to override the licensing mechanism. Importantly, both tumor- and cytokine-activated NK cells induced DC maturation in a TNFSF14-dependent manner. The coupling of TNFSF14 production to tumor-sensing NK-cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. Furthermore, regulation by NK cell licensing helps to safeguard against TNFSF14 production in response to healthy tissues.Natural killer (NK) cells play an important role in protecting the host against viral infection and cancer. As well as having potent cytotoxic activity, NK cells are endowed with immunoregulatory activity (1, 2). For example, NK cell activation induces the production of chemokines, such as macrophage inflammatory protein-1α (MIP-1α) and IL-8, and proinflammatory cytokines, such as IFN-γ, GM-CSF, and TNF-α. These molecules regulate the recruitment and activity of numerous immune cell types (1, 2). Importantly, NK cells can promote development of T-cell responses via NK–dendritic cell (DC) interactions that favor both DC maturation and NK-cell activation (3–5), with NK cell-derived IFN-γ skewing T-cell differentiation toward the Th1 phenotype (6, 7).Cytotoxic activity and cytokine production are coupled to signaling pathways downstream of a repertoire of activating and inhibitory receptors; signals from activating receptors (including NKG2D, DNAM-1, and 2B4, as well as the natural cytotoxicity receptors NKp30, NKp44, and NKp46) compete with signals from inhibitory receptors such as the killer cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A heterodimers to regulate activation. In addition, NK cells express CD16, the low-affinity receptor for IgG, conferring antibody-dependent cellular cytotoxicity (8–10). Activation thus coordinates the killing of target cells, the induction of inflammation, and the promotion of adaptive immunity. This potent cytotoxicity and proinflammatory activity must be strictly controlled to minimize damage to healthy tissue. Functional competency of unstimulated NK cells is achieved via a process termed “licensing” or “education” (11–14). Licensing ensures that only those NK cells expressing inhibitory receptors for self-MHC class I can respond to target cells and NK cells that lack inhibitory receptors for self-MHC class I molecules are rendered hyporesponsive, preventing them from attacking healthy cells expressing normal levels of MHC class I molecules.We have analyzed the consequences of human NK cell activation by tumor cells. Our results reveal induction of the TNF superfamily member 14 (TNFSF14), also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT) (15). We show that activated NK cells produce TNFSF14 in response to different stimuli, that tumor cells induce TNFSF14 production by licensed NK cells, and that TNFSF14-producing NK cells aid DC maturation during NK–DC cross-talk.     

Direct evidence for a magnetic f-electron–mediated pairing mechanism of heavy-fermion superconductivity in CeCoIn5

To identify the microscopic mechanism of heavy-fermion Cooper pairing is an unresolved challenge in quantum matter studies; it may also relate closely to finding the pairing mechanism of high-temperature superconductivity. Magnetically mediated Cooper pairing has long been the conjectured basis of heavy-fermion superconductivity but no direct verification of this hypothesis was achievable. Here, we use a novel approach based on precision measurements of the heavy-fermion band structure using quasiparticle interference imaging to reveal quantitatively the momentum space (k-space) structure of the f-electron magnetic interactions of CeCoIn₅. Then, by solving the superconducting gap equations on the two heavy-fermion bands Ekα,β with these magnetic interactions as mediators of the Cooper pairing, we derive a series of quantitative predictions about the superconductive state. The agreement found between these diverse predictions and the measured characteristics of superconducting CeCoIn₅ then provides direct evidence that the heavy-fermion Cooper pairing is indeed mediated by f-electron magnetism.Superconductivity of heavy fermions is of abiding interest, both in its own right (1–7) and because it could exemplify the unconventional Cooper pairing mechanism of high-temperature superconductors (8–11). Heavy-fermion compounds are intermetallics containing magnetic ions in the 4f- or 5f-electronic state within each unit cell. At high temperatures, each f-electron is localized at a magnetic ion (Fig. 1A). At low temperatures, interactions between f-electron spins (red arrows Fig. 1A) lead to the formation of a narrow but the subtly curved f-electron band εkf near the chemical potential (red curve, Fig. 1B), and Kondo screening hybridizes this band with the conventional c-electron band εkc of the metal (black curve, Fig. 1B). As a result, two new heavy-fermion bands Ekα,β (Fig. 1C) appear within a few millielectron volts of the Fermi energy. Their electronic structure is controlled by the hybridization matrix element s_k for interconversion of conduction c-electrons to f-electrons and vice-versa, such thatEkα,β=εkc+εkf2±(εkc−εkf2)2+sk2.[1]The momentum structure of the narrow bands of hybridized electronic states (Eq. 1 and Fig. 1C, blue curves at left) near the Fermi surface then directly reflects the form of magnetic interactions encoded within the parent f-electron band εkf. It is these interactions that are conjectured to drive the Cooper pairing (1–5) and thus the opening up of a superconducting energy gap (Fig. 1C, yellow curves at right).Open in a separate windowFig. 1.Effects of f-electron magnetism in a heavy-fermion material. (A) The magnetic subsystem of CeCoIn₅ consists of almost localized magnetic f-electrons (red arrows) with a weak hopping matrix element yielding a very narrow band with strong magnetic interactions between the f-electron spins. (B) The heavy f-electron band is shown schematically in red and the light c-electron band in black. (C) On the left, schematic of the result of hybridizing the c- and f-electrons in B into new composite electronic states referred to as heavy fermions (blue). On the right, the opening of a superconducting energy gap is schematically shown by back-bending bands near the chemical potential. The microscopic interactions driving Cooper pairing of these states, and thus of heavy-fermion superconductivity, have not been identified unambiguously for any heavy-fermion compound.     

高原医院三氧消毒杀菌机空气消毒效果观察

为了解三氧消毒机在高原对空气消毒的效果,在手术后使用三氧消毒杀菌机作用不同时间,进行空气采样检测。结果,开机作用0.5、1.0、1.5h后,空气中菌数合格率分别为70％。80％、85％;作用1.5h对空气自然菌杀灭率为87.5％。作用前后空气细菌平均含量经统计分析,差异有非常显著性(P<0.001)。在高原环境下,使用三氧消毒杀菌机对手术室空气作用1.5h可达到较好的消毒效果。     

Stat5b Is Essential for Natural Killer Cell–mediated Proliferation and Cytolytic Activity

We have analyzed the immune system in Stat5-deficient mice. Although Stat5a^−/− splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b^−/− splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor β chain (IL-2Rβ), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation in activated splenocytes, freshly isolated splenocytes from Stat5b^−/− mice exhibited greatly diminished proliferation in response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2– and IL-15–mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell–mediated proliferation and cytolytic activity.