Endoplasmic Reticulum Stress-Mediated Apoptosis Involved in Indirect Recognition Pathway Blockade Induces Long-Term Heart Allograft Survival

Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effectively knock down CD80 and CD86 expression. T cells primed by these DCs inhibited allogeneic responses. Administration of recipient DCs loaded with alloantigen after CD80 and CD86 blockade prolonged cardiac allograft survival. We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group. In addition, these T cells expressed high expression of GRP78 than controls, indicating activation of unfolded protein responses. Upregulation of CHOP expression among these cells suggested that the endoplasmic reticulum stress (ERS) response switched to a proapoptotic response. Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection

Myeloid-Derived Suppressor Cells Participate in Preventing Graft Rejection

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells and have a tremendous potential to suppress immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection, transplantation, and other pathological conditions and can potently suppress T-cell function. Here, we discuss recent findings that describe the molecular mechanisms of MDSCs suppressing T-cell immune responses as well as recent observations that MDSCs may have roles in transplant tolerance

Controlled oxygen doping in highly dispersed Ni-loaded g-C3N4 nanotubes for efficient photocatalytic H2O2 production

Hydrogen peroxide (HO) is both a key component in several industrial processes and a promising liquid fuel. The production of HO by solar photocatalysis is a suitable strategy to convert and store solar energy into chemical energy. Here we report an oxygen-doped tubular g-CN with uniformly dispersed nickel nanoparticles for efficient photocatalytic HO generation. The hollow structure of the tubular g-CN provides a large surface with a high density of reactive sites and efficient visible light absorption during the photocatalytic reaction. The oxygen doping and Ni loading enable a fast separation of photogenerated charge carriers and a high selectivity toward the two-electron process during the oxygen reduction reaction (ORR). The optimized composition, Ni/OtCN, displays an HO production rate of 2464 μmol g·h, which is eightfold higher than that of bulk g-CN under visible light irradiation (λ > 420 nm), and achieves an apparent quantum yield (AQY) of 28.2% at 380 nm and 14.9% at 420 nm.IREC and ICN2 acknowledge funding from Generalitat de Catalunya, projects 2017 SGR 1246 and 2017 SGR 327, respectively. The authors thank the support from the project COMBENERY (PID2019-105490RB-C32) and NANOGEN (PID2020-116093RB-C43), funded by MCIN/ AEI/10.13039/501100011033/. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCAProgramme / Generalitat de Catalunya. Baoying Li and Jianbin Chen greatly appreciate the financial support from the National Natural Science Foundation of China (Nos. 22171154 & 21801144), the Youth Innovative Talents Recruitment and Cultivation Program of Shandong Higher Education, The Project Supported by the Foundation (No. ZZ20190312) of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology (Shandong Academy of Sciences)

Development of a synchronous recording and photo-stimulating electrode in multiple brain neurons

The investigation of brain networks and neural circuits involves the crucial aspects of observing and modulating neurophysiological activity. Recently, opto-electrodes have emerged as an efficient tool for electrophysiological recording and optogenetic stimulation, which has greatly facilitated the analysis of neural coding. However, implantation and electrode weight control have posed significant challenges in achieving long-term and multi-regional brain recording and stimulation. To address this issue, we have developed a mold and custom-printed circuit board-based opto-electrode. We report successful opto-electrode placement and high-quality electrophysiological recordings from the default mode network (DMN) of the mouse brain. This novel opto-electrode facilitates synchronous recording and stimulation in multiple brain regions and holds promise for advancing future research on neural circuits and networks

A multi-wavelength mid-IR laser based on BaGa4Se7 optical parametric oscillators

A multi-wavelength mid-IR laser consisting of 3.05 μm, 4.25 μm, and 5.47 μm BaGa4Se7(BGSe)optical parametric oscillators (OPOs) switched by DKDP electro-optic switches with one 10 Hz/7.6 ns pumping wave is demonstrated. Maximum energies at 3.05 μm, 4.25 μm, and 5.47 μm are 1.35 mJ, 1.03 mJ, and 0.56 mJ, respectively, corresponding to optical-to-optical conversion efficiencies of 9.4%, 7.6%, and 4.2%. To the best of our knowledge, this study is the first of generation of three mid-IR wavelength lasers using electro-optic switches. Furthermore, this study provides a viable solution for a high-energy or high-power, compact, or even portable multi-wavelength mid-IR laser device that employs a single pumping wave

Environmental Adaptation: Genomic Analysis of the Piezotolerant and Psychrotolerant Deep-Sea Iron Reducing Bacterium Shewanella piezotolerans WP3

Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature

Unilateral Multifocality and Bilaterality Could Be Two Different Multifocal Entities in Patients with Papillary Thyroid Microcarcinoma

Objective. Multifocality within an affected lobe (unilateral multifocality) or two lobes (bilaterality) is commonly denoted as multifocality without differentiation. Recently, there has been molecular evidence indicating that unilateral multifocality and bilaterality could be two different entities. However, few studies concerning the comparison between these two different multifocality entities have been reported. Design. A retrospective cohort study. Methods. From 2010 to 2013, in total, 949 consecutive patients with papillary thyroid microcarcinoma (PTMC) were enrolled and further divided into four groups based on multifocality status. Unilateral multifocality and bilaterality were analyzed by binary logistic regression along with other clinicopathological factors. Results. Unilateral multifocality, instead of bilaterality, was correlated with central neck metastasis (CNM) in both univariate and multivariate analyses. Group IV (unilateral multifocality and bilaterality coexist) had the highest CNM rate. Group III (unilateral multifocality) had a higher CNM rate than group II (bilaterality, single lesion in each lobe), with a significant difference (p=0.032). Similar lateral neck metastasis tendency was observed among the four groups. In the multivariate analysis, only unilateral multifocality and bilaterality which coexisted were correlated with CNM. Moreover, 9 cases had a recurrence, with the recurrence rate ranking top in group IV (3.6%), second in group III (2.8%), and third in group II (1.2%). The difference was significant (p=0.021). Conclusion. Unilateral multifocality and bilaterality could be two different multifocal entities in patients with PTMC. Unilateral multifocality serving as a prognostic factor indicated a worse prognosis than bilaterality on neck metastasis. When the two factors coexisted in PTMC, patients had the highest risk of CNM and possibly local recurrence compared with those with either risk factor alone

MiR-301a Promotes Colorectal Cancer Cell Growth and Invasion by Directly Targeting SOCS6

Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC