摘要：Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cells first caught researchers' attention and became great success in chimeric antigen receptor-based immunotherapy. However, engineered T cells seem to hit their bottleneck when resistance of cancerous cells, less encouraging responses in solid tumors and unwanted toxicities to the host remain to be ***, innate immune cells get to join the race. Representatives such as natural killer cells, natural killer T cells, γδT cells and macrophages also prove to be well redirected with chimeric antigen receptors. Compared to chimeric antigen receptor engineered T cells, these engineered innate immune cells may possess multiple targeting and killing mechanisms, have the potential to crack the barrier of solid tumors and have less side effects in the host. Besides, possible universal access to cell resources and improvements in expansion and transduction techniques make these cells promising candidates with huge potential in translational medicine. Therefore, innate immune cells claim a brand-new dimension and are likely to supplement T cells greatly in the field of chimeric antigen receptor-based immunotherapy.

摘要：Searching for more potent and less toxic HMBA related agents. Methods. Human erythroleukemia cell K562, murine erythroleukemia cell (MEL) and its sub line MEL DS19 were used as target cells to select a cell line which is the most sensitive to HMBA, then analyzed the activity of inducing differentiati on of two new designed HMBA derivatives: HMBPA [hexamethylenebi (3 pyridin) ami de] and Co HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology, c ytochemical and molecular biology techniques. Results. We found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive, B+～76%). Co HDTA can inhibit the growth of MEL DS19, but induces differentiation just in a small population (B+ 2%～4.5%). Between 0.02～5μmo l/L, HMBPA induces 3%～8% cells committed to differentiation with little inhib ition of cell proliferation. 1μmol/L HMBPA and 2mmol/L HMBA together, can obvio usly increase the percentage of differentiated cell (B+～ 72%), inhibit DNA sy nthesis and accelerate β globin transcription. Conclusion. The new HMBA derivatives may provide potential cancer differentiatio n inducers.

摘要：The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic *** adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to *** a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment *** this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is *** by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and *** study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm *** indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis *** thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation ***,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to *** microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.

摘要：Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues,and have been given the name"telocytes".Recent studies have demonstrated the potential roles of telocytes in heart development,renewal,and ***,further research on the functions of telocytes is limited by the complicated in vivo *** study was designed to construct engineered heart tissue(EHT)as a three-dimensional model in vitro to better understand the role of telocytes in the architectural organization of the *** were constructed by seeding neonatal cardiomyocytes in collagen/Matrigel scaffolds followed by culture under persistent static *** in EHTs were identified by histology,toluidine blue staining,immunofluorescence,and transmission electron *** results from histology and toluidine blue staining demonstrated widespread putative telocytes with compact toluidine blue-stained nuclei,which were located around *** from the cell bodies showed a characteristic dichotomous branching pattern and formed networks in *** revealed positive staining of telocytes for CD34 and vimentin with typical moniliform prolongations.A series of electron microscopy images further showed that typical telocytes embraced the cardiomyocytes with their long prolongations and exhibited a marked appearance of nursing cardiomyocytes during the construction of *** finding highlights the great importance of telocytes in the architectural organization of *** also suggests that EHT is an appropriate physical and pathological model system in vitro to study the roles of telocytes during heart development and regeneration.

摘要：Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s *** lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic *** work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral *** ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin *** vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone *** proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C *** healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in *** as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral *** rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

摘要：Intracellular electrophysiological research is vital for biological and medical *** planar microelectrode arrays(MEAs)have disadvantages in recording intracellular action potentials due to the loose cell-electrode *** investigate intracellular electrophysiological signals with high sensitivity,electroporation was used to obtain intracellular *** this study,a biosensing system based on a nanoporous electrode array(NPEA)integrating electrical perforation and signal acquisition was established to dynamically and sensitively record the intracellular potential of cardiomyocytes over a long period of ***,nanoporous electrodes can induce the protrusion of cell membranes and enhance cell-electrode interfacial coupling,thereby facilitating effective *** signals over the entire recording process can be quantitatively and segmentally analyzed according to the signal changes,which can equivalently reflect the dynamic evolution of the electroporated cardiomyocyte *** believe that the low-cost and high-performance nanoporous biosensing platform suggested in this study can dynamically record intracellular action potential,evaluate cardiomyocyte electroporation,and provide a new strategy for investigating cardiology pharmacological science.

摘要：Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.

摘要：·AIM:To investigate the independent pathogenic role of high serum gamma-glutamyl transferase (GGT) levels, sociodemographic data, dietary and environmental risk factors for visual disability (VD). ·METHODS:This was a case-control study, run in 200 black Congolese patients managed in Saint Joseph Hospital Ophthalmology Division from Kinshasa town. Logistic regression model was used to identify determinants of VD (n = 58) among sex, age, cigarette smoking, alcohol abuse, rural-urban migration, education levels, aging ≥60 years, intake of red Beans, Safou fruit and Taro leaves, lipid profile, residence, socioeconomic status, and GGT. ·RESULTS:After adjusting for confounding factors, we identified migration (OR=3.7 95% CI:1.2-11.3; P =0.023), low education level (OR=3.1 95% CI 1.1-8.5; P =0.026), no intake of Safou fruit (OR=34.2 95% CI 11.5-102; P < 0.0001), age ≥60 years (OR=2.5 95% CI 1.01-6.5; P = 0.049), and serum GGT ≥10U/L (OR=3.6 95% CI 1.3-9.6; P = 0.012) as the significant and independent determinants of VD. ·CONCLUSION:VD appears as a major public health problem in Central Africa to be prevented or delayed by control of migration, lifestyle changes, antioxidant supplements, appropriate diet, nutrition education, and blocking of oxidative stress.

摘要：Manganese peroxidases (MnPs) are interesting enzymes in protein engineering, aimed at maximizing industrial bioprocesses such as lignin degradation and biofuel production. cDNA of the secreted short-type of MnP from Phlebia radiata (Pr-MnP3) has been successfully engineered and amplified by polymerase chain reaction (PCR). Five mutant genes (E40H, E44H, E40H/E44H, D186H and D186N) of recombinant Phlebia radiata MnP3 (rPr-MnP3) were generated. The wild-type and the mutant genes were expressed in Escherichia coli (W3110 strain) and the resultant body proteins were lysed, purified and refolded into active enzymes. 6% - 7% recovery of pure and fully active rPr-MnP3 for wild-type and mutants were obtained and the availability of rPr-MnP3 enzymes will greatly facilitate its structure-function relationships studies. rPr-MnP3 mass was characterised using SDS-PAGE and MALDI-TOF mass spectrometry. Molecular weight of both the wild-type and mutant rPr-MnP3 enzymes was approximately 36 kDa. This describes the spectral characterization of the wild-type and mutant rPr-MnP3 enzymes with are very close similarities;substantially high spin haem enzymes. Therefore we report the engineering, cloning, expression, refolding/activation of MnP3 genes and preliminary characterization of the wild-type and mutant Phlebia radiata MnP3 enzymes.

摘要：Malaria still threatens global health seriously *** the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug ***,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of *** simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported ***-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo *** structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.