Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization.

The upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single-cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region-specific epithelial and mesenchymal subpopulations and then deduced region-specific ligand-receptor pairs mediating mesenchymal-epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ-specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper MD development, and provides a manageable list of potential genes, pathways, and region-specific cell subtypes for future functional studies.

First report of a p.Cys484Tyr Notch3 mutation in a CADASIL patient with acute bilateral multiple subcortical infarcts-case report and brief review.

BACKGROUND: CADASIL(Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)is an inherited small vessel disease caused by mutations in NOTCH3 gene. Although NOTCH3 has numerous hotspots of gene mutations, mutations in exons 9 are rare. The p.C484T gene mutation type associated with it has not been reported in any relevant cases yet. Furthermore, CADASIL patients rarely present with acute bilateral multiple subcortical infarcts. CASE PRESENTATION: We report the case of a Chinese female patient with CADASIL who experienced "an acute bilateral subcortical infarction" because of"hemodynamic changes and hypercoagulability". In genetic testing, we discovered a new Cys484Tyr mutation in exon 9, which has also been found in the patient's two daughters. CONCLUSIONS: It is important to note that this discovery not only expands the mutation spectrum of Notch3 mutations in CADASIL patients, but also examines the mechanism behind acute bilateral subcortical infarction in CADASIL patients via case reviews and literature reviews, in order to provide some clinical recommendations for early intervention, diagnosis, and treatment in similar cases in the future.

Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

Ex vivo development of the entire mouse fetal reproductive tract by using microdissection and membrane-based organ culture techniques.

Ex vivo explant culture is an appealing alternative to in vivo studies on fetal reproductive organ development. There is extensive literature on ex vivo methods of growing the fetal gonad. However, a method for culturing the whole fetal reproductive tract that has a different shape and size has not been documented. Here, with careful dissection and proper tissue orientation, we successfully cultured the entire bicornuate reproductive tracts from mouse embryos of both sexes on the Transwell insert membrane. The cultured reproductive tract system undergoes sexually dimorphic establishment and region-specific morphogenesis comparable to in vivo development of their counterparts. To test this culture method's applications, we used chemical treatment (dihydrotestosterone and BMS 564929) and genetic cellular ablation mouse model (Gli1-CreER; Rosa-DTA) to investigate the roles of androgen signaling and Gli1+ mesenchyme in Wolffian duct development. Dihydrotestosterone and BMS 564929 promoted the ectopic maintenance of Wolffian ducts in cultured XX tissues. The efficient and specific elimination of Gli1+ mesenchyme was successfully achieved in the cultured tissues, resulting in defective coiling of Wolffian ducts. These results demonstrate the amenability of this organ culture method for chemical and genetic manipulations that are otherwise difficult to study in vivo. Taken together, the establishment of this organ culture method provides a valuable tool complementary to in vivo studies for understanding fetal reproductive tract development in mice.

A case of acute basilar artery occlusion due to atherosclerotic disease revascularized by drug-coated balloon dilation.

Acute basilar artery occlusion (ABAO) accounts for 1% of all ischemic stroke cases, but has a high rate of severe complications and mortality (75-91%). Intracranial atherosclerosis is an significant cause of ischemic stroke. Revascularization using stents has shown good efficacy. However, intra-stent thrombosis and in-stent restenosis (ISR) are significant complications following stent placement. Drug-coated balloons (DCB), coated with the anti-proliferative drug paclitaxel (an inhibitor of endothelial proliferation), can prevent in-stent restenosis. Successful use of DCB dilation in the coronary and lower extremity vasculature has been reported. In our case, a 68-year-old Chinese male with ABAO was successfully revascularized by DCB dilation and showed dramatic improvement in stroke symptoms. This report may inform future treatment of patients with ABAO.

[Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels].

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Morphogenesis of the female reproductive tract along antero-posterior and dorso-ventral axes is dependent on Amhr2+ mesenchyme in mice†.

Morphogenesis of the female reproductive tract is regulated by the mesenchyme. However, the identity of the mesenchymal lineage that directs the morphogenesis of the female reproductive tract has not been determined. Using in vivo genetic cell ablation, we identified Amhr2+ mesenchyme as an essential mesenchymal population in patterning the female reproductive tract. After partial ablation of Amhr2+ mesenchymal cells, the oviduct failed to develop its characteristic coiling due to decreased epithelial proliferation and tubule elongation during development. The uterus displayed a reduction in size and showed decreased cellular proliferation in both epithelial and mesenchymal compartments. More importantly, in the uterus, partial ablation of Amhr2+ mesenchyme caused abnormal lumen shape and altered the direction of its long axis from the dorsal-ventral axis to the left-right axis (i.e., perpendicular to the dorsal-ventral axis). Despite these morphological defects, epithelia underwent normal differentiation into secretory and ciliated cells in the oviduct and glandular epithelial cells in the uterus. These results demonstrated that Amhr2+ mesenchyme can direct female reproductive tract morphogenesis by regulating epithelial proliferation and lumen shape without affecting the differentiation of epithelial cell types.

PrGeFNE: Predicting disease-related genes by fast network embedding.

Identifying disease-related genes is of importance for understanding of molecule mechanisms of diseases, as well as diagnosis and treatment of diseases. Many computational methods have been proposed to predict disease-related genes, but how to make full use of multi-source biological data to enhance the ability of disease-gene prediction is still challenging. In this paper, we proposed a novel method for predicting disease-related genes by using fast network embedding (PrGeFNE), which can integrate multiple types of associations related to diseases and genes. Specifically, we first constructed a heterogeneous network by using phenotype-disease, disease-gene, protein-protein and gene-GO associations; and low-dimensional representation of nodes is extracted from the network by using a fast network embedding algorithm. Then, a dual-layer heterogeneous network was reconstructed by using the low-dimensional representation, and a network propagation was applied to the dual-layer heterogeneous network to predict disease-related genes. Through cross-validation and newly added-association validation, we displayed the important roles of different types of association data in enhancing the ability of disease-gene prediction, and confirmed the excellent performance of PrGeFNE by comparing to state-of-the-art algorithms. Furthermore, we developed a web tool that can facilitate researchers to search for candidate genes of different diseases predicted by PrGeFNE, along with the enrichment analysis of GO and pathway on candidate gene set. This may be useful for investigation of diseases' molecular mechanisms as well as their experimental validations. The web tool is available at http://bioinformatics.csu.edu.cn/prgefne/.

Lateral Monolayer MoSe2 -WSe2 p-n Heterojunctions with Giant Built-In Potentials.

2D transition metal dichalcogenides (TMDs) have exhibited strong application potentials in new emerging electronics because of their atomic thin structure and excellent flexibility, which is out of field of tradition silicon technology. Similar to 3D p-n junctions, 2D p-n heterojunctions by laterally connecting TMDs with different majority charge carriers (electrons and holes), provide ideal platform for current rectifiers, light-emitting diodes, diode lasers and photovoltaic devices. Here, growth and electrical studies of atomic thin high-quality p-n heterojunctions between molybdenum diselenide (MoSe2 ) and tungsten diselenide (WSe2 ) by one-step chemical vapor deposition method are reported. These p-n heterojunctions exhibit high built-in potential (≈0.7 eV), resulting in large current rectification ratio without any gate control for diodes, and fast response time (≈6 ms) for self-powered photodetectors. The simple one-step growth and electrical studies of monolayer lateral heterojunctions open up the possibility to use TMD heterojunctions for functional devices.

Inch-sized aligned polymer nanofiber films with embedded CH3NH3PbBr3 nanocrystals: electrospinning fabrication using a folded aluminum foil as the collector.

Perovskite nanocrystal embedded polymer nanofibers with polarized emissions are interesting materials for down-shifting applications. By using a folded aluminum foil as a collector, we fabricated inch-size aligned polymer nanofiber films with embedded CH3NH3PbBr3 nanocrystals by adapting an electrospinning technique. It was found that the addition of an appropriate amount of cyanoethyl cellulose (CEC) makes the dispersion of MAPbBr3 in the nanofibers more uniform. Using a precursor solution with MAPbBr3 of 10% and CEC of 1 wt%, the resulting nanofiber films show strong polarized emission with quantum yields up to 51%. The emission dichroic ratio and emission polarization ratio can reach 5.21 and 0.43, respectively. These polarized emissive films can be potentially applied as down converters for liquid crystal display backlights and other polarization selective photonic devices.

Three-dimensional mesostructures as high-temperature growth templates, electronic cellular scaffolds, and self-propelled microrobots.

Recent work demonstrates that processes of stress release in prestrained elastomeric substrates can guide the assembly of sophisticated 3D micro/nanostructures in advanced materials. Reported application examples include soft electronic components, tunable electromagnetic and optical devices, vibrational metrology platforms, and other unusual technologies, each enabled by uniquely engineered 3D architectures. A significant disadvantage of these systems is that the elastomeric substrates, while essential to the assembly process, can impose significant engineering constraints in terms of operating temperatures and levels of dimensional stability; they also prevent the realization of 3D structures in freestanding forms. Here, we introduce concepts in interfacial photopolymerization, nonlinear mechanics, and physical transfer that bypass these limitations. The results enable 3D mesostructures in fully or partially freestanding forms, with additional capabilities in integration onto nearly any class of substrate, from planar, hard inorganic materials to textured, soft biological tissues, all via mechanisms quantitatively described by theoretical modeling. Illustrations of these ideas include their use in 3D structures as frameworks for templated growth of organized lamellae from AgCl-KCl eutectics and of atomic layers of WSe2 from vapor-phase precursors, as open-architecture electronic scaffolds for formation of dorsal root ganglion (DRG) neural networks, and as catalyst supports for propulsive systems in 3D microswimmers with geometrically controlled dynamics. Taken together, these methodologies establish a set of enabling options in 3D micro/nanomanufacturing that lie outside of the scope of existing alternatives.

Lead-Free Double Perovskite Cs2 SnX6 : Facile Solution Synthesis and Excellent Stability.

Long-term instability and possible lead contamination are the two main issues limiting the widespread application of organic-inorganic lead halide perovskites. Here a facile and efficient solution-phase method is demonstrated to synthesize lead-free Cs2 SnX6 (X = Br, I) with a well-defined crystal structure, long-term stability, and high yield. Based on the systematic experimental data and first-principle simulation results, Cs2 SnX6 displays excellent stability against moisture, light, and high temperature, which can be ascribed to the unique vacancy-ordered defect-variant structure, stable chemical compositions with Sn4+ , as well as the lower formation enthalpy for Cs2 SnX6 . Additionally, photodetectors based on Cs2 SnI6 are also fabricated, which show excellent performance and stability. This study provides very useful insights into the development of lead-free double perovskites with high stability.

Localization of neonatal Fc receptor for IgG in aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus) of different ages.

BACKGROUND: The neonatal Fc receptor (FcRn) plays a crucial role in transporting IgG and associated antigens across polarized epithelial barriers in mucosal immunity. However, it was not clear that FcRn expression in aggregated lymphoid nodules area (ALNA) in abomasum, a unique and important mucosal immune structure discovered only in Bactrian camels. In the present study, 27 Alashan Bactrian camels were divided into the following five age groups: fetus (10-13 months of gestation), young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). The FcRn expressions were observed and analyzed in detail with histology, immunohistochemistry, micro-image analysis and statistical methods. RESULTS: The results showed that the FcRn was expressed in mucosal epithelial cells of ALNA from the fetus to the old group, although the expression level rapidly declined in old group; moreover, after the ALNA maturated, the FcRn expression level in the non-follicle-associated epithelium (non-FAE) was significantly higher than that in FAE (P < 0.05). In addition, the FcRn was also expressed in the vessel endothelium, smooth muscle tissue, and macrophages and dendritic cells (DCs) of secondary lymphoid follicles (sLFs). CONCLUSIONS: It was demonstrated that FcRn was mainly expressed in non-FAE, the effector sites, although which was expressed in FAE, the inductive sites for mucosal immunity. And it was also expressed in DCs and macrophages in sLFs of all ages of Bactrian camels. The results provided a powerful evidence that IgG (including HCAb) could participate in mucosal immune response and tolerance in ALNA of Bactrian camels through FcRn transmembrane transport.

Expression and characterization of bifunctional fusion proteins possessing antitumor and thrombolytic function for targeting therapy.

It is a usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. ΔSEC2, N-terminal deletion of 17 amino acids and C-terminal deletion of 132 amino acids, retained antitumor activity of SEC2. ΔSak, N-terminal deletion of 10 amino acids, had thrombolytic activity and specificity advantages. By utilizing bioactivities of ΔSEC2 and ΔSak, ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed. Octreotide is a tumor targeting peptide and it can be combined with somatostatin (SST) receptors of tumor surface in ligand-receptor binding way. It can be used to increase specificity for tumor therapy. Based on previous studies, DNA sequence encoding octreotide gene was inserted into plasmid pET-28a-Δsec2-Δsak and pET-28a-Δsak-Δsec2. After expression and purification, fusion proteins could significantly stimulate proliferation of mouse spleen lymphocyte, obviously inhibit the growth of human gastric carcinoma BGC-823, and have thrombolytic activity, indicating that fusion proteins retained bioactivities of staphylococcal enterotoxin C2 and Sak. Furthermore, tumor binding capacity of fusion protein was confirmed through the coimmunoprecipitation method. The result showed that they could bind SST receptor 2 antibody, indicating that fusion proteins could be specifically targeted to tumor surface. It has important significance and may be used for targeted therapy.

[SIC algorithm based model updating for near infrared analysis of Salvia miltiorrhiza alcohol extraction process].

The near-infrared (NIR) spectroscopy for offline monitoring of alcohol extraction process of Salvia miltiorrhiza was investigated, with high performance liquid chromatography (HPLC) determination of value for reference. The partial least squares method was adopted to establish the tanshinone ⅡA quantitative calibration model, so as to detect extraction process of Salvia miltiorrhiza. Because the differences between batches of raw materials may endanger the robustness of the original model, the simple interval calculation (SIC) was applied in updating the near-infrared quantitative model for traditional Chinese medicine extraction process for the first time, and compared with Random Selection (RS) method. SIC's final updating results showed that root mean square with cross validation (RMSECV), root mean square error of prediction (RMSEP) and residual predictive deviation (RPD) of tanshinone ⅡA were 0.006 8 g•L⁻¹, 0.005 4 g•L⁻¹ and 3.14, respectively; but RS' final updating results showed that RMSECV, RMSEP and RPD were 0.006 4 g•L⁻¹, 0.006 8 g•L⁻¹ and 2.50, respectively. This study suggested that SIC is superior to RS, and provided a research foundation for quality control and monitoring of S. miltiorrhiza extraction process in the future.

Balancing Industry and Drug Policy Objectives in the Pharmaceutical Sector: The Case of China.

Objectives This article assessed the balance between industry and drug policy objectives in the pharmaceutical sector in China. Methods The articles were mainly identified through databases such as Elsevier, Google Scholar, and SpringerLink, among others. Related articles were mainly separated into three categories: studies on drug policies, studies related to China's new health-care reform policy, and studies concerning patent policies. Results A relatively healthy environment for continuous innovation and drug patent protection in the pharmaceutical industry has been created in China, and the public's drug benefits have also significantly improved. However, the balance between industrial and drug policy objectives in the pharmaceutical sector in China requires additional attention. Discussion and conclusions The results suggest that the government should pay more attention to incentivizing enterprises' innovation, but the current Essential Medicines System in China has limited innovation. Hence, the mechanism for selecting essential medicines should be reformed, and certain appropriate and reasonably innovative medicines should be included. Additionally, medicine coverage, especially the coverage of essential drugs for primary care should be expanded to improve public health benefits. Furthermore, the pharmaceutical industry should be incorporated into the prospective National Drug Policy to achieve a balance between public benefits and pharmaceutical industry development in the future.

Distribution of immunoglobulin G antibody secretory cells in small intestine of Bactrian camels (Camelus bactrianus).

BACKGROUND: To explore the morphological evidence of immunoglobulin G (IgG) participating in intestinal mucosal immunity, 8 healthy adult Bactrian camels used. First, IgG was successfully isolated from their serum and rabbit antibody against Bactrian camels IgG was prepared. The IgG antibody secretory cells (ASCs) in small intestine were particularly observed through immumohistochemical staining, then after were analyzed by statistical methods. RESULTS: The results showed that the IgG ASCs were scattered in the lamina propria (LP) and some of them aggregated around of the intestinal glands. The IgG ASCs density was the highest from middle segment of duodenum to middle segment of jejunum, and then in ended segment of jejunum and initial segment of ileum, the lowest was in initial segment of duodenum, in middle and ended segment of ileum. CONCLUSIONS: It was demonstrated that the IgG ASCs mainly scattered in the effector sites of the mucosal immunity, though the density of IgG ASCs was different in different segment of small intestine. Moreover, this scatted distribution characteristic would provide a morphology basis for research whether IgG form a full-protection and immune surveillance in mucosal immunity homeostasis of integral intestine.

[Rapid multi-elemental analysis on four precious Tibetan medicines based on LIBS technique].

The laser-induced breakdown spectroscopy (LIBS) was applied to perform a qualitative elementary analysis on four precious Tibetan medicines, i. e. Renqing Mangjue, Renqing Changjue, 25-herb coral pills and 25-herb pearl pills. The specific spectra of the four Tibetan medicines were established. In the experiment, Nd: YAG and 1 064 nm-baseband pulse laser were adopted to collect the spectra. A laser beam focused on the surface of the samples to generate plasma. Its spectral signal was detected by using spectrograph. Based on the National Institute of Standard and Technology (NIST) database, LIBS spectral lines were indentified. The four Tibetan medicines mainly included Ca, Na, K, Mg and other elements and C-N molecular band. Specifically, Fe was detected in Renqing Changjue and 25-herb pearl pills; heavy mental elements Hg and Cu were shown in Renqing Mangjue and Renqing Changjue; Ag was found in Renqing Changjue. The results demonstrated that LIBS is a reliable and rapid multi-element analysis on the four Tibetan medicines. With Real-time, rapid and nondestructive advantages, LIBS has a wide application prospect in the element analysis on ethnic medicines.

Construction of novel chimeric proteins through the truncation of SEC2 and Sak from Staphylococcus aureus.

It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44 kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29 kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic.

Electronanofiltration Membranes with a Bilayer Charged Structure Enable High Li+/Mg2+ Selectivity.

Achieving separation of lithium and magnesium with similar radii is crucial for the current lithium extraction technology from salt lakes, which usually possess a high lithium-to-magnesium ratio. Herein, we proposed the facile sequential interfacial polymerization (SIP) approach to construct electronanofiltration membranes (ENFMs) with a bilayer charged structure consisting of a high positively charged surface and a negatively charged sublayer. The trimesoyl chloride (TMC) concentration was adjusted to enhance the -COOH content and negative charge of the polyamide sublayer to promote Li+ migration, and then the quaternized polyethylenimine was introduced to the membrane surface by the SIP process to increase the positive charge density on the surface of the ENFMs, which would block the migration of Mg2+ and enhance the Li+/Mg2+ selectivity of the ENFMs. The optimal quaternary-modified ENFMs achieved outstanding selectivity for Li+/Mg2+ (49.85) and high Li+ flux (4.10 × 10-8 mol cm-2 s-1) at a current density of 10 mA cm-2. Moreover, in simulated brines with low lithium concentration and high Mg2+/Li+ ratio, the optimal ENFMs also displayed elevated Li+/Mg2+ selectivity (>45), highlighting the substantial promise of the membranes for practical applications.