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الحزام والطريق : ماذا ستقدم الصين للعالم ؟
حاول هذا الكتاب الذي بين أيديكم أن يقدم إجابات معيارية قياسية لكافة الأسئلة الجذرية المتعلقة بمبادرة \"الحزام والطريق\" والتي تقدم الصين من خلالها حلا لاستغلال قدراتها التي لا تتوقف عن التنامي لتتبوأ مقعدها كمحرك للنمو الاقتصادي العالمي في المستقبل و المتشوقين للتعرف على الملامح الحقيقية للتنين الصيني وتجربته مع سياسة الإصلاح والانفتاح طوال أكثر من ثلاثين عاما ومبادرته الجديدة ذات السمات الفوق عولمية نقدم الحزام والطريق ماذا ستقدم الصين للعالم.
Book
Chemoenzymatic synthesis of glycoengineered IgG antibodies and glycosite-specific antibody–drug conjugates
Glycoengineering of IgG antibodies and glycosite-specific antibody–drug conjugates is an important tool for enhancing their therapeutic efficacy. Tang
et al
. describe a protocol for efficient and homogeneous chemoenzymatic antibody glycoengineering.
Glycoengineered therapeutic antibodies and glycosite-specific antibody–drug conjugates (gsADCs) have generated great interest among researchers because of their therapeutic potential. Endoglycosidase-catalyzed
in vitro
glycoengineering technology is a powerful tool for IgG Fc (fragment cystallizable)
N
-glycosylation remodeling. In this protocol, native heterogeneously glycosylated IgG
N
-glycans are first deglycosylated with a wild-type endoglycosidase. Next, a homogeneous
N
-glycan substrate, presynthesized as described here, is attached to the remaining
N
-acetylglucosamine (GlcNAc) of IgG, using a mutant endoglycosidase (also called endoglycosynthase) that lacks hydrolytic activity but possesses transglycosylation activity for glycoengineering. Compared with
in vivo
glycoengineering technologies and the glycosyltransferase-enabled
in vitro
engineering method, the current approach is robust and features quantitative yield, homogeneous glycoforms of produced antibodies and ADCs, compatibility with diverse natural and non-natural glycan structures, convenient exploitation of native IgG as the starting material, and a well-defined conjugation site for antibody modifications. Potential applications of this method cover a broad scope of antibody-related research, including the development of novel glycoengineered therapeutic antibodies with enhanced efficacy, site-specific antibody–drug conjugation, and site-specific modification of antibodies for fluorescent labeling, PEGylation, protein cross-linking, immunoliposome formation, and so on, without loss of antigen-binding affinity. It takes 5–8 d to prepare the natural or modified
N
-glycan substrates, 3–4 d to engineer the IgG
N
-glycosylation, and 2–5 d to synthesize the small-molecule toxins and prepare the gsADCs.
Journal Article
Assessment of the Energy Efficiency Improvement of Twenty-Five Countries: A DEA Approach
Since energy efficiency and energy improvement are viewed as two of the most important keys of sustainable management, research on energy has become popular and captured much more attention. The current paper aimed to measure the energy efficiency of 25 countries with carbon dioxide (CO2) emissions as well as their energy efficiency improvement. First, a data envelopment analysis (DEA) slack-based model (SBM) was employed to obtain efficiency scores. Second, the Malmquist Productivity Index (MPI) was then used to examine the improvement during the period of 2010–2017. Findings of this study showed that developed countries had a more balanced development between gross domestic product (GDP) growth and CO2 emissions by using the same inputs as developing countries. Additionally, the findings revealed that India and China, being the two largest population countries, achieved improved energy intensity during 2010–2017; however; their energy consumption and CO2 emissions continued to grow, leading them to being the two worst countries in terms of energy efficiency.
Journal Article
CTLA-4 expression by B-1a B cells is essential for immune tolerance
CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life. This impaired immune homeostasis results from B-1a cell dysfunction upon loss of CTLA-4. Therefore, CTLA-4-deficient B-1a cells up-regulate epigenetic and transcriptional activation programs and show increased self-replenishment. These activated cells further internalize surface IgM, differentiate into antigen-presenting cells and, when reconstituted in normal IgH-allotype congenic recipient mice, induce GCs and Tfh cells expressing a highly selected repertoire. These findings show that CTLA-4 regulation of B-1a cells is a crucial immune-regulatory mechanism.
CTLA-4 is an important co-inhibitory receptor for T cells. Here, the authors show that CTLA-4 also has a function on B-1a cells, as conditional deletion results in activation of these cells and knockout mice develop an autoimmune profile.
Journal Article
Monovalent lanthanide(I) in borozene complexes
Lanthanide (Ln) elements are generally found in the oxidation state +II or +III, and a few examples of +IV and +V compounds have also been reported. In contrast, monovalent Ln(+I) complexes remain scarce. Here we combine photoelectron spectroscopy and theoretical calculations to study Ln-doped octa-boron clusters (LnB
8
−
, Ln = La, Pr, Tb, Tm, Yb) with the rare +I oxidation state. The global minimum of the LnB
8
−
species changes from
C
s
to
C
7v
symmetry accompanied by an oxidation-state change from +III to +I from the early to late lanthanides. All the
C
7v
-LnB
8
−
clusters can be viewed as a monovalent Ln(I) coordinated by a η
8
-B
8
2−
doubly aromatic ligand. The B
7
3−
, B
8
2−
, and B
9
−
series of aromatic boron clusters are analogous to the classical aromatic hydrocarbon molecules, C
5
H
5
−
, C
6
H
6
, and C
7
H
7
+
, respectively, with similar trends of size and charge state and they are named collectively as “borozenes”. Lanthanides with variable oxidation states and magnetic properties may be formed with different borozenes.
The most common oxidation state for lanthanides is +3. Here the authors use photoelectron spectroscopy and theoretical calculations to study half-sandwich complexes where a lanthanide center in the oxidation state +1 is bound to an aromatic wheel-like B
8
2-
ligand.
Journal Article
Newly observed X(4630): a new charmoniumlike molecule
Very recently, the LHCb Collaboration at the Large Hadron Collider at CERN observed new resonance X(4630). The X(4630) is decoded as a charmoniumlike molecule with hidden-strange quantum number well in the one-boson-exchange mechanism. Especially, the study of its hidden-charmed decays explicitly shows the dominant role of J/ψϕ among all allowed hidden-charmed decays of the X(4630), which enforces the conclusion of X(4630) as a charmoniumlike molecule. The discovery of the X(4630) is a crucial step of constructing charmoniumlike molecule zoo.
Journal Article
Spherical trihedral metallo-borospherenes
The discovery of borospherenes unveiled the capacity of boron to form fullerene-like cage structures. While fullerenes are known to entrap metal atoms to form endohedral metallofullerenes, few metal atoms have been observed to be part of the fullerene cages. Here we report the observation of a class of remarkable metallo-borospherenes, where metal atoms are integral parts of the cage surface. We have produced La
3
B
18
–
and Tb
3
B
18
–
and probed their structures and bonding using photoelectron spectroscopy and theoretical calculations. Global minimum searches revealed that the most stable structures of Ln
3
B
18
–
are hollow cages with
D
3
h
symmetry. The B
18
-framework in the Ln
3
B
18
–
cages can be viewed as consisting of two triangular B
6
motifs connected by three B
2
units, forming three shared B
10
rings which are coordinated to the three Ln atoms on the cage surface. These metallo-borospherenes represent a new class of unusual geometry that has not been observed in chemistry heretofore.
Borospherenes are the boron-based analogs of fullerene cages. Here, the authors report a class of Ln
3
B
18
–
metallo-borospherenes with unusual spherical trihedron geometry, in which the lanthanide atoms surprisingly form a part of the cage surface.
Journal Article
Modulating IgG effector function by Fc glycan engineering
IgG antibodies contain a conserved N-glycosylation site on the Fc domain to which a complex, biantennary glycan is attached. The fine structures of this glycan modulate antibody effector functions by affecting the binding affinity of the Fc to diverse Fc receptor family members. For example, core fucosylation significantly decreases antibody-dependent cellular cytotoxicity (ADCC), whereas terminal α2,6-sialylation plays a critical role in the anti-inflammatory activity of human i.v. immunoglobulin therapy. The effect of specific combinations of sugars in the glycan on ADCC remains to be further addressed, however. Therefore, we synthesized structurally well-defined homogeneous glycoforms of antibodies with different combinations of fucosylation and sialylation and performed side-by-side in vitro FcγR-binding analyses, cell-based ADCC assays, and in vivo IgG-mediated cellular depletion studies. We found that core fucosylation exerted a significant adverse effect on FcγRIIIA binding, in vitro ADCC, and in vivo IgG-mediated cellular depletion, regardless of sialylation status. In contrast, the effect of sialylation on ADCC was dependent on the status of core fucosylation. Sialylation in the context of core fucosylation significantly decreased ADCC in a cell-based assay and suppressed antibody-mediated cell killing in vivo. In contrast, in the absence of fucosylation, sialylation did not adversely impact ADCC.
Journal Article
Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection
Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (
Lyso700D
) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR
Staphylococcus aureus
(MRSA) and
Acinetobacter baumannii
(AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.
There is increased demand for effective, broad-spectrum treatment options against severe, multi-drug resistant bacterial infections. Here, Wang et al describe an effective photodynamic therapy based on the adoptive transfer of macrophages loaded with a lysosomal photosensitiser.
Journal Article