High-Entropy Alloy Array via Liquid Metal Nanoreactor.

High-entropy alloy (HEA) nanostructures arranged into well-defined configurations hold great potential for accelerating the development of electronics, photonics, catalysis, and device integration. However, the random nucleation induced by the disparity in physicochemical properties of multiple elements makes it challenging to achieve single-particle synthesis at the patterned preset sites in the high-entropy scenario. Herein, the liquid metal nanoreactor strategy is proposed to realize the construction of HEA arrays. The coalescence of the liquid metal driven by the tendency to decrease surface energy provides a restricted environment for the nucleation and growth to form single HEA particles at the preset locations, which can be regarded as a self-confinement reaction. Liquid metal endowing a low diffusion energy barrier on the substrate and a high diffusivity of the alloy system can dynamically promote the aggregation process. As a result, the HEA array is prepared with elements up to eleven and possesses uniform periodicity, which exhibits excellent holography response in a broad spectrum. This work injects new vitality into the construction of HEA nanopatterns and provides an excellent platform for propelling their fundamental research and applications.

Delivery of exogenous miR-19b by Wharton's Jelly Mesenchymal Stem Cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism.

Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3ß (GSK3ß) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.

Controllable synthesis of high-entropy alloys.

High-entropy alloys (HEAs) involving more than four elements, as emerging alloys, have brought about a paradigm shift in material design. The unprecedented compositional diversities and structural complexities of HEAs endow multidimensional exploration space and great potential for practical benefits, as well as a formidable challenge for synthesis. To further optimize performance and promote advanced applications, it is essential to synthesize HEAs with desired characteristics to satisfy the requirements in the application scenarios. The properties of HEAs are highly related to their chemical compositions, microstructure, and morphology. In this review, a comprehensive overview of the controllable synthesis of HEAs is provided, ranging from composition design to morphology control, structure construction, and surface/interface engineering. The fundamental parameters and advanced characterization related to HEAs are introduced. We also propose several critical directions for future development. This review can provide insight and an in-depth understanding of HEAs, accelerating the synthesis of the desired HEAs.

Synthesis of Ultrathin High-Entropy Oxides with Phase Controllability.

High-entropy oxides (HEOs) with an ultrathin geometric structure are especially expected to exhibit extraordinary performance in different fields. The phase structure is deemed as a key factor in determining the properties of HEOs, rendering their phase control synthesis tempting. However, the disparity in intrinsic phase structures and physicochemical properties of multiple components makes it challenging to form single-phase HEOs with the target phase. Herein, we proposed a self-lattice framework-guided strategy to realize the synthesis of ultrathin HEOs with desired phase structures, including rock-salt, spinel, perovskite, and fluorite phases. The participation of the Ga assistor was conducive to the formation of the high-entropy mixing state by decreasing the formation energy. The as-prepared ultrathin spinel HEOs were demonstrated to be an excellent catalyst with high activity and stability for the oxygen evolution reaction in water electrolysis. Our work injects new vitality into the synthesis of HEOs for advanced applications and undoubtedly expedites their phase engineering.

Assessing the impact of the 2018 tetanus guidelines on knowledge and practices of emergency physicians in trauma patients: a national survey study.

Background: Tetanus remains a significant public health issue in China, with the approach of anti-tetanus prophylaxis in the emergency department resulting in both overuse, particularly of human tetanus immune globulin (TIG), and underuse with the tetanus vaccine. This is largely due to the absence of updated guidelines on tetanus prophylaxis before 2018. Our study aimed to evaluate the effects of the 2018 Chinese tetanus guidelines on the knowledge and practices of emergency physicians about tetanus prevention in trauma patients. Methods: From November 2019 to April 2020, we conducted a web-based survey involving 499 emergency physicians. The survey included a questionnaire covering knowledge, attitudes, and practices related to tetanus. We assessed the influence of the 2018 tetanus guidelines on the knowledge and practices of emergency physicians related to tetanus prevention for patients with trauma using multiple regression analysis. Results: The survey results showed that only 45.3% of the participants had received formal training on tetanus immunization, despite 53.3% reporting the availability of tetanus vaccines at their institutions. Physicians typically prescribed tetanus antitoxin or human TIG instead of tetanus toxoid (TT) to treat injuries, regardless of the patient's TT vaccination history. Among the respondents, those who were aware of the 2018 tetanus guidelines had higher mean scores on the general knowledge, risk knowledge, and treatment knowledge scales, with increases of 6%, 13%, and 9%, respectively, compared to those who were unaware of the guidelines. Awareness of the 2018 tetanus guidelines was associated with a high level of knowledge, as indicated by the general knowledge score, recommendation knowledge score, and total knowledge score, after adjusting for the effects of all variables on the knowledge, attitudes, and practices of the participants. A high level of education was also associated with a high level of knowledge indicated by the recommendation knowledge score and total knowledge score. Conclusions: Our study highlights a substantial gap in the attitudes, knowledge, and practices of emergency physicians in China regarding tetanus immunization. The results suggest an urgent need to promote the Chinese Expert Consensus Guidelines on tetanus to improve emergency physicians' knowledge and competence in tetanus prophylaxis. The findings underscore the importance of enhancing physicians' awareness of the latest guidelines to ensure appropriate and effective treatment for patients with tetanus-prone injuries.

Liquid metal for high-entropy alloy nanoparticles synthesis.

High-entropy alloy nanoparticles (HEA-NPs) show great potential as functional materials1-3. However, thus far, the realized high-entropy alloys have been restricted to palettes of similar elements, which greatly hinders the material design, property optimization and mechanistic exploration for different applications4,5. Herein, we discovered that liquid metal endowing negative mixing enthalpy with other elements could provide a stable thermodynamic condition and act as a desirable dynamic mixing reservoir, thus realizing the synthesis of HEA-NPs with a diverse range of metal elements in mild reaction conditions. The involved elements have a wide range of atomic radii (1.24-1.97 Å) and melting points (303-3,683 K). We also realized the precisely fabricated structures of nanoparticles via mixing enthalpy tuning. Moreover, the real-time conversion process (that is, from liquid metal to crystalline HEA-NPs) is captured in situ, which confirmed a dynamic fission-fusion behaviour during the alloying process.

Distinct profiles of bile acid metabolism caused by gut microbiota in kidney transplantation recipients revealed by 16S rRNA gene sequencing.

The present study sought to characterise the gut microbiota of subjects with kidney transplantation and healthy control to identify the distinct gut microbiota and analyse their potential function. We found that gut microbiota abundance had significant differences in subjects between the two groups. Line Discriminant Analysis (LDA) Effect Size (LEfSe) analysis showed that the bacterial taxa were differentially represented between the two groups, and the potential biomarkers at different taxonomic levels in kidney transplant recipients were Streptococcus, Enterococcaceae, and Ruminococcus. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) Functional Inference analyses suggested that the difference in gut microbiota between the two groups was correlated with bile acid metabolism. In conclusion, gut microbiota abundance is different between the two groups, which is related to bile acid metabolism, and may influence the metabolic homeostasis of allograft recipients.

Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS. METHODS: After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People's Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). RESULTS: In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan-Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P  = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09-0.62). The levels of platelet aggregation rate ( P  < 0.001), cholesterol ( P  = 0.028), and low-density lipoprotein cholesterol ( P  = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. CONCLUSION: Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04260828.

Antibiotic ampicillin induces immune tolerance in renal transplantation by regulating the proportion of intestinal flora in mice.

Objectives: There are significant differences in the composition of intestinal flora in renal transplant recipients before and after an operation, which has a great impact on the prognosis of renal transplantation. The purpose of this project is to study the effect of intestinal flora imbalance on renal transplantation. Methods: The animal model of renal transplantation was established after intestinal flora imbalance (mice pretreated with compound antibiotics), or the animal model of renal transplantation was established after being pretreated with single antibiotics. HE, PAS, and Masson staining was used to detecting the histopathological changes of transplanted renal. The expression of inflammatory factors and infiltration of inflammatory cells of renal tissue were respectively been detected by ELISA kit and flow cytometry. Results: Antibiotic pretreatment restored weight loss, and decreased serum creatinine level in mice after renal transplantation. The tissue staining, ELISA assay, and flow cytometry data showed that antibiotic pretreatment alleviated injury of the renal allograft, inhibited the inflammatory factors levels, and reduced inflammatory cell infiltration in mice after renal transplantation. Furthermore, single antibiotic, especially ampicillin pretreatment can also play the same role as compound antibiotics, such as restoring weight loss, decreasing serum creatinine level, alleviating renal allograft injury, inhibiting inflammatory factors levels, and reducing inflammatory cell infiltration in mice after renal transplantation. Conclusions: Antibiotic ampicillin may inhibit inflammatory cell infiltration after renal transplantation by regulating the proportion of intestinal flora in mice, to reduce renal injury and play a role in renal protection.

Microstructural Evolution of SK85 Pearlitic Steel Deformed by Heavy Cold Rolling.

The microstructural evolution of SK85 pearlitic steel cold-rolled up to a 90% rolling reduction was characterized by scanning electron microscopy with electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). SK85 steel exhibits excellent cold rolling performance. The interlamellar spacing of pearlite is refined obviously and a tensile strength of 2318 MPa can be reached for SK85 steel after 90% rolling reduction, an increase of 83% from 1264 MPa before rolling. The EBSD observation indicates that the {001} <110> texture becomes pronounced at a 90% rolling reduction in cold-rolled Sk85 steel. A propagation and multiplication of dislocations occur during rolling as the kernel average misorientation (KAM) angles significantly increase from 0.72° to 2.11°. The XRD analysis reveals that bcc ferrite is transformed into a bct structure at a 90% rolling reduction. The strengthening mechanism was discussed.

Dual-activity nanozyme to initiate tandem catalysis for doubly enhancing ATP-depletion anti-tumor therapy.

Nanozymes can regulate metabolism to achieve precise anti-tumor therapy. However, the application of nanozymes with single catalytic properties is limited by complex tumor microenvironment (TME). Herein, we report a rarely discovered nanozyme ruthenium (Ru), which has double catalytic activity of glucose-oxidase-like (GOx-like) activity and peroxidase-like (POD-like) activity. Importantly, the GOx-like activity of Ru was proposed for the first time, which can catalyze glucose and O2 to product H2O2. And then, Ru nanozyme can connect the tandem catalysis to enhance various tumor therapy. Firstly, the atovaquone (ATO) and Ru NPs were covered with a hybrid membrane of tumor cells and liposomes to obtain Ru@ATO-Lip/M with homologous targeting. Due to the enhanced permeability and retention (EPR) effect and the tumor targeting, the Ru@ATO-Lip/M NPs could be efficiently delivered to tumor and taken up by tumor cells. Subsequently, the acidic environment of tumor activated Ru to catalyze H2O2 producing OH (Fenton-like reaction). Meanwhile, newly discovered ability of Ru catalyzed glucose and O2 to produce gluconic acid and H2O2, which provided sufficient substrates (H2O2) for continuously generating more OH. Therefore, Ru nanozyme aggravated the starvation and chemodynamic therapy (CDT). Further, ATO improved the hypoxia of the tumor microenvironment, achieving steadily synergistic anti-tumor effect. This study verified the glucose oxidase-like properties of Ru NPs for the first time, and the strategy enhanced the synergistic anti-tumor effects by CDT and starvation therapy, which provided a basis for further exploration of Ru nanozyme activity and application on antitumor.

MoS2 nanoflower-mediated enhanced intratumoral penetration and piezoelectric catalytic therapy.

The absence of lymphatic vessels in tumors leads to the retention of interstitial fluid, and the formation of an inverse pressure difference between the tumor and blood vessels hinders drug delivery deep into the tumor, which leads to tumor recurrence and metastasis. Therefore, we designed a novel strategy to downregulate tumor interstitial fluid pressure (TIFP) by water splitting in the tumor interstitium based on piezoelectric catalysis nanomedicine. First, the chemotherapeutic drug doxorubicin (DOX) was loaded on the piezoelectric catalytic material MoS2 and then encapsulated with tumor cell membrane (CM) to obtain MD@C. MD@C could not only target the tumor through homologous targeting but, more importantly, also triggered piezoelectric catalytic water splitting under ultrasound (US) stimulation; as a result, the TIFPs of U14 and PAN02 tumor-bearing mice were reduced to 57.14% and 45.5%, respectively, and the tumor inhibition rates of MD@C were 96.75% and 99.21%, which increased the perfusion of blood-derived drugs in the tumors. Moreover, the hydroxyl radicals generated by piezoelectric catalysis could effectively inhibit the growth of tumors in combination with DOX. Consequently, the piezoelectric catalytic water splitting strategy of MD@C can enhance drug delivery, providing a new universal platform for the treatment of solid malignant tumors.

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.

Most of the neurodegenerative diseases and aging are associated with reactive oxygen species (ROS) or other intracellular damaging agents that challenge the genome integrity of the neurons. As most of the mature neurons stay in G0/G1 phase, replication-uncoupled DNA repair pathways including BER, NER, SSBR, and NHEJ, are pivotal, efficient, and economic mechanisms to maintain genomic stability without reactivating cell cycle. In these progresses, polymerases are prominent, not only because they are responsible for both sensing and repairing damages, but also for their more diversified roles depending on the cell cycle phase and damage types. In this review, we summarized recent knowledge on the structural and biochemical properties of distinct polymerases, including DNA and RNA polymerases, which are known to be expressed and active in nervous system; the biological relevance of these polymerases and their interactors with neuronal degeneration would be most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair; furthermore, the vicious cycle of the trinucleotide repeat (TNR) and impaired DNA repair pathway is also discussed. Unraveling the mechanisms and contextual basis of the role of the polymerases in DNA damage response and repair will promote our understanding about how long-lived postmitotic cells cope with DNA lesions, and why disrupted DNA repair contributes to disease origin, despite the diversity of mutations in genes. This knowledge may lead to new insight into the development of targeted intervention for neurodegenerative diseases.

Metagenomic Next-Generation Sequencing Reveals the Profile of Viral Infections in Kidney Transplant Recipients During the COVID-19 Pandemic.

Background: To study the clinical application of metagenomic next-generation sequencing (mNGS) in the detection of viral infections in kidney transplant recipients (KTRs) during the COVID-19 pandemic. Methods: Using mNGS technology, 50 human fluid samples of KTRs were detected, including 20 bronchoalveolar lavage fluid (BALF) samples, 21 urine samples and 9 blood samples. The detected nucleic acid sequences were compared and analyzed with the existing viral nucleic acid sequences in the database, and the virus infection spectrum of KTRs was drawn. Results: The viral nucleic acids of 15 types of viruses were detected in 96.00% (48/50) of the samples, of which 11 types of viruses were in BALF (95.00%, 19/20), and the dominant viruses were torque teno virus (TTV) (65.00%; 13/20), cytomegalovirus (CMV) (45.00%; 9/20) and human alphaherpesvirus 1 (25.00%; 5/20). 12 viruses (95.24%, 20/21) were detected in the urine, and the dominant viruses were TTV (52.38%; 11/21), JC polyomavirus (52.38%; 11/21), BK polyomavirus (42.86%; 9/21), CMV (33.33%; 7/21) and human betaherpesvirus 6B (28.57%; 6/21). 7 viruses were detected in the blood (100.00%, 9/9), and the dominant virus was TTV (100.00%; 9/9). Four rare viruses were detected in BALF and urine, including WU polyomavirus, primate bocaparvovirus 1, simian virus 12, and volepox virus. Further analysis showed that TTV infection with high reads indicated a higher risk of acute rejection (P < 0.05). Conclusions: mNGS detection reveals the rich virus spectrum of infected KTRs, and improves the detection rate of rare viruses. TTV may be a new biomarker for predicting rejection.

Prognostic factors and clinical efficacy of second-line treatments of Pneumocystis jirovecii pneumonia for non-HIV patients after first-line treatment failure.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now. METHODS: Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared. RESULTS: Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P < 0.001), coinfection with CMV (69 vs. 47%, P = 0.035), and bacteremia (59 vs. 10%, P < 0.001). A total of 49 patients received second-line treatment on the basis of TMP/SMX, and 28 (57.1%) of them responded to the treatment. No clinical parameter, including selection of different therapies, was found to be significantly associated with second-line treatment failure. Further, the prognosis of different second-line therapies showed no drug or drug combination strategy superior to others. The primaquine group had lower 90-day mortality rate (45.9%) but showed no statistically significant difference compared with the non-primaquine group (64.6%). The patients in the clindamycin plus primaquine group had the lowest in-hospital mortality rate (22.2%, P = 0.042) among different second-line therapies, although the in-hospital mortality of the primaquine group was not significantly different from that of the non-primaquine group. The differences in 28 day mortality and overall mortality rates were not statistically significant, too. CONCLUSION: CMV infection and bacteremia were risk factors significantly associated with treatment failure of TMP/SMX. The response and survival rates of second-line treatment, including clindamycin, primaquine, and caspofungin, were poor, maybe clindamycin plus primaquine as second line treatment was better than other treatment strategies. These results suggest that clinicians should carefully evaluate whether the treatment of TMP/SMX has failed due to a coinfection rather than hastily changing to a second-line drug when the patient worsens.

Effect of Tempering Temperature on Microstructure and Sulfide Stress Cracking of 125 Ksi Grade Casing Steel.

The influence of tempering temperature on the microstructure of 0.5Cr0.4W steels was investigated by scanning electron microscope, and the roles of grain boundary character, dislocation, and Taylor factor in sulfide stress cracking (SSC) resistance were interpreted using the election backscattered diffraction technique. The 0.5Cr0.4W steels tempered at 690 °C, 700 °C, and 715 °C all showed tempered martensites. The specimen tempered at 715 °C exhibited a higher critical stress intensity factor (KISSC) of 34.58 MPa·m0.5, but the yield strength of 800 MPa did not meet the criterion of 125 ksi (862 MPa) grade. When the specimen was tempered at 690 °C, the yield strength reached 960 MPa and the KISSC was only 21.36 MPa·m0.5, displaying poorer SSC resistance. The 0.5Cr0.4W steel tempered at 700 °C showed a good combination of yield strength (887 MPa) and SSC resistance (KISSC: 31.16 MPa·m0.5). When increasing the tempering temperature, the local average misorientation and Taylor factor of the 0.5Cr0.4W steels were decreased. The reduced dislocation density, and greater number of grains amenable to slippage, produced less hydrogen transport and a lower crack sensitivity. The SSC resistance was, thus, increased, owing to the minor damage to hydrogen aggregation. Therefore, 700 °C is a suitable tempering temperature for 0.5Cr0.4W casing steel.

Strong Magnetic-Field-Engineered Porous Template for Fabricating Hierarchical Porous Ni-Co-Zn-P Nanoplate Arrays as Battery-Type Electrodes of Advanced All-Solid-State Supercapacitors.

The sluggish charge transport kinetics that exist in the energy storage process of all-solid-state supercapacitors (ASSSCs) can be improved by designing open hierarchical porous structures for binder-free electrodes. Herein, a template-directed strategy is developed to fabricate open hierarchical porous Ni-Co-Zn-P nanoplate arrays (NCZP6T) through phosphating the electrodeposited NiCo-LDH nanosheets loaded on a template. At first, porous conductive NiZn alloy nanoplate arrays are rationally devised as the template by a strong magnetic field (SMF)-assisted electrodeposition. The Lorentz force caused by coupling the SMF with the electrical current induces a magnetohydrodynamic (MHD) flow (including the micro-MHD flow), which homogenizes the deposition coating, tunes the nucleation and growth of the NiZn alloy, and produces pores in the nanoplates. The open hierarchical porous structure offers a larger specific surface area and pore volume for accelerating charge transport and gives a synergistic effect between the inner porous conductive NiZn array template and the outer electrochemical active phosphides for high-performance hybrid ASSSCs. Accordingly, the battery-type electrode of NCZP6T shows a much higher specific capacitance of 3.81 F cm-2 at 1 mA cm-2, enhanced rate capability, and remarkable cycling stability at progressively varying current densities. Finally, the NCZP6T//FeS ASSSC delivers a high energy density of 77 µW h cm-2 at a large power density of 12 mW cm-2, outperforming most state-of-the-art supercapacitors.

Exosomes Secreted by Mesenchymal Stem Cells Induce Immune Tolerance to Mouse Kidney Transplantation via Transporting LncRNA DANCR.

Mesenchymal stem cells induce kidney transplant tolerance by increasing regulatory T (Treg) cells. Bone marrow mesenchymal stem cell exosomes (BMMSC-Ex) promote Treg cell differentiation. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is expressed in BMMSCs and can be encapsulated in exosomes. We aimed to explore the role of DANCR in BMMSC-Ex in immune tolerance after kidney transplantation and related mechanism. The isogenic/allograft kidney transplantation mouse model was established, and levels of serum creatinine (SCr) were determined. Hematoxylin-eosin staining was conducted to detect the inflammation, and immunohistochemistry was performed to detect the infiltration of CD4+ T cells. Levels of IFN-γ, IL-17, and IL-2 were examined by ELISA. Flow cytometry was conducted to determine Treg cells. In the allograft group, the inflammatory response was severe, CD4+ T cell infiltration, SCr levels, and plasma rejection-related factors were up-regulated, while injection of BMMSC-Ex reversed the results. BMMSC-Ex increased Treg cells in kidney transplantation mice. Interference with DANCR reversed the promoting effect of BMMSC-Ex on Treg cell differentiation. DANCR bound to SIRT1, promoted ubiquitination and accelerated its degradation. The injection of BMMSC-Ex (after interference with DANCR) promoted SIRT1 levels, inflammatory response, CD4+ T cell infiltration, SCr levels, and plasma rejection related factors' expression, while Treg cells were decreased. LncRNA DANCR in BMMSC-Ex promoted Treg cell differentiation and induced immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4+ T cells.

circCEP128 Knockdown Suppresses Bladder Cancer Progression via Regulating microRNA-515-5p/SDC1 Axis.

BACKGROUND: Dysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood. METHODS: The levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay. RESULTS: circCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1. CONCLUSION: circCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.

Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.

Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.