Prediction of delayed graft function by early salivary microbiota following kidney transplantation.

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis.

Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

A SARS-CoV-2 RBD vaccine fused to the chemokine MIP-3α elicits sustained murine antibody responses over 12 months and enhanced lung T-cell responses.

Background: Previous studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN). Methods: BALB/c mice aged 6-8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α. In a small-scale (n = 3/group) experiment, mice immunized IM with electroporation were followed up for serum antibody concentrations over a period of 1 year and for bronchoalveolar antibody levels at the termination of the study. Following IN immunization with unencapsulated plasmid DNA (n = 6/group), mice were evaluated at 11 weeks for serum antibody concentrations, quantities of T cells in the lungs, and IFN-γ- and TNF-α-expressing antigen-specific T cells in the lungs and spleen. Results: At 12 months postprimary vaccination, recipients of the IM vaccine incorporating MIP-3α had significantly, approximately threefold, higher serum antibody concentrations than recipients of the vaccine not incorporating MIP-3α. The area-under-the-curve analyses of the 12-month observation interval demonstrated significantly greater antibody concentrations over time in recipients of the MIP-3α vaccine formulation. At 12 months postprimary immunization, only recipients of the fusion vaccine had concentrations of serum-neutralizing activity deemed to be effective. After intranasal immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs significantly above those of PBS controls. Low levels of serum antibody responses were obtained following IN immunization. Conclusion: Although requiring separate IM and IN immunizations for optimal immunization, incorporating MIP-3α in a SARS-CoV-2 vaccine construct demonstrated the potential of a stable and easily produced vaccine formulation to provide the extended antibody and T-cell responses that may be required for protection in the setting of emerging SARS-CoV-2 variants. Without electroporation, simple, uncoated plasmid DNA incorporating MIP-3α administered intranasally elicited lung T-cell responses.

Association between salivary microbiota and renal function in renal transplant patients during the perioperative period.

Introduction: Renal transplantation is an effective treatment for the end stage renal disease (ESRD). However, how salivary microbiota changes during perioperative period of renal transplant recipients (RTRs) has not been elucidated. Methods: Five healthy controls and 11 RTRs who had good recovery were enrolled. Saliva samples were collected before surgery and at 1, 3, 7, and 14 days after surgery. 16S rRNA gene sequencing was performed. Results: There was no significant difference in the composition of salivary microbiota between ESRD patients and healthy controls. The salivary microbiota of RTRs showed higher operational taxonomic units (OTUs) amount and greater alpha and beta diversity than those of ESRD patients and healthy controls, but gradually stabilized over time. At the phylum level, the relative abundance of Actinobacteria, Tenericutes and Spirochaetes was about ten times different from ESRD patients or healthy controls for RTRs overall in time. The relative abundance of Bacteroidetes, Fusobacteria, Patescibacteria, Leptotrichiaceae and Streptococcaceae was correlated with serum creatinine (Scr) after renal transplantation. Discussion: In short, salivary microbiota community altered in the perioperative period of renal transplantation and certain species of salivary microbiota had the potential to be a biomarker of postoperative recovery.

Biofilms in wound healing: A bibliometric and visualised study.

Bibliometric analyses are often used as a means of visualising the knowledge base and associated trends and patterns in a target scientific field based on a quantitative review of the corresponding literature. In this study, we explore the current status of research pertaining to biofilms in wound healing and elucidate trends in this research space. Through this process, we gain insight into findings from papers indexed in the Web of Science Core Collection. These references were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. The results provide a fresh perspective regarding global trends and hotspots in biofilm-related wound healing research. These findings also offer a foundation that researchers can use to identify active hotspots of scientific interest to guide further research endeavours.

An intranasal stringent response vaccine targeting dendritic cells as a novel adjunctive therapy against tuberculosis.

Lengthy tuberculosis (TB) treatment is required to overcome the ability of a subpopulation of persistent Mycobacterium tuberculosis (Mtb) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the RelMtb-mediated stringent response. We developed a novel therapeutic DNA vaccine containing a fusion of the relMtb gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3α/CCL20. To augment mucosal immune responses, intranasal delivery was also evaluated. We found that intramuscular delivery of the MIP-3α/relMtb (fusion) vaccine or intranasal delivery of the relMtb (non-fusion) vaccine potentiate isoniazid activity more than intramuscular delivery of the DNA vaccine expressing relMtb alone in a chronic TB mouse model (absolute reduction of Mtb burden: 0.63 log10 and 0.5 log10 colony-forming units, respectively; P=0.0002 and P=0.0052), inducing pronounced Mtb-protective immune signatures. The combined approach involving intranasal delivery of the DNA MIP-3α/relMtb fusion vaccine demonstrated the greatest mycobactericidal activity together with isoniazid when compared to each approach alone (absolute reduction of Mtb burden: 1.13 log10, when compared to the intramuscular vaccine targeting relMtb alone; P<0.0001), as well as robust systemic and local Th1 and Th17 responses. This DNA vaccination strategy may be a promising adjunctive approach combined with standard therapy to shorten curative TB treatment, and also serves as proof of concept for treating other chronic bacterial infections.

Loss-tolerant quantum multi-party key agreement without quantum storage.

Quantum key distribution (QKD) and quantum key agreement (QKA) are two main branches of key establishment in quantum cryptography. However, the research of QKA falls far behind that of QKD, especially in practicability. The main reason is that QKA needs to resist not only the outside eavesdropping but also the participant cheating. Resisting dishonest participant is more difficult than resisting outside eavesdropping, especially when the apparatuses are imperfect. Actually, existing QKA protocols cannot tolerate the channel loss and have to rely on stable quantum storage. To solve this problem, we give a new quantum multi-party key agreement protocol based on the error-correcting code. Our protocol is loss tolerant, and the participants can measure the received qubits immediately in one of two conjugate bases, without storage, so our protocol can eliminate the requirement of quantum storage. Besides, our protocol is more fair because it can partially discriminate dishonest participants' cheating from outside eavesdropping (previously, these two attacks are generally checked simultaneously via decoy states but cannot be discriminated), as a result, dishonest participants generally will not cheat at the cost of losing good reputation.

IFNα and 5-Aza-2'-deoxycytidine combined with a dendritic-cell targeting DNA vaccine alter tumor immune cell infiltration in the B16F10 melanoma model.

Introduction: DNA vaccines containing a fusion of the gene encoding chemokine MIP-3α (CCL20), the ligand for CCR6 on immature dendritic cells (DCs), to melanoma-associated antigen genes have enhanced anti-tumor immunity and efficacy compared to those lacking the chemokine gene. Previous work has shown that type-I interferon (IFNα or IFN) and 5-Aza-2'-deoxycytidine (5Aza) significantly enhance the therapeutic benefit of DNA vaccines as measured by reduced tumor burden and improved mouse survival. Methods: Here, we explored mouse intratumoral immune correlates underlying the therapeutic benefit of this combination regimen (vaccine, IFN, and 5Aza) as compared to vaccine alone and IFN and 5Aza without vaccine, focusing on chemokine mRNA expression by qRT-PCR and inflammatory cellular infiltration into the tumor microenvironment (TME) by flow cytometry and immunohistochemistry (IHC). Results: The combination group significantly upregulated intratumoral mRNA expression of key immune infiltration chemokines XCL1 and CXCL10. Flow cytometric analyses of tumor suspensions exhibited greater tumor infiltration of CD8+ DCs, CCR7+ DCs, and NK cells in the combination group, as well as reduced levels of myeloid-derived suppressor cells (MDSCs) in vaccinated groups. The mice receiving combination therapy also had greater proportions of effector/memory T-cells (Tem), in addition to showing an enhanced infiltration of Tem and central memory CD8+ T-cells, (Tcm). Tem and Tcm populations both correlated with smaller tumor size. Immunohistochemical analysis of tumors confirmed that CD8+ cells were more abundant overall and especially in the tumor parenchyma with combination therapy. Discussion: Efficient targeting of antigen to immature DCs with a chemokine-fusion vaccine offers a potential alternative approach to classic and dendritic cell-based vaccines. Combining this approach with IFNα and 5Aza treatments significantly improved vaccine efficacy. This treatment creates an environment of increased inflammatory chemokines that facilitates the trafficking of CD8+ DCs, NK cells, and CD8+ T-cells, especially memory cells, while reducing the number of MDSCs. Importantly, in the combination group, CD8+ cells were more able to penetrate the tumor mass in addition to being more numerous. Further analysis of the pathways engaged by our combination therapy is expected to provide additional insights into melanoma pathogenesis and facilitate the development of novel treatment strategies.

NEDD4 Induces K48-Linked Degradative Ubiquitination of Hepatitis B Virus X Protein and Inhibits HBV-Associated HCC Progression.

Neural precursor cell expressed developmentally downregulated gene 4 (NEDD4) plays two opposite roles in carcinogenesis. It has been reported that NEDD4 inhibits hepatocellular carcinoma (HCC) progression; however, little is known about its potential function and molecular mechanism in HCC in the context of hepatitis B virus (HBV) infection. In this study, we analyzed NEDD4 expression in 199 HCC specimens with or without HBV infection and observed that NEDD4 expression was unrelated to HBV exposure in HCC tumor tissue but that high NEDD4 expression conferred better overall survival (OS) and progression-free survival (PFS) than low NEDD4 expression in patients with HBV-associated HCC. Upregulation of NEDD4 inhibited proliferation, migration and invasion in HBV-related HCC cell lines. We demonstrated that NEDD4 interacts with HBV X protein (HBx) and that HBx upregulation could reverse the suppression of proliferation and mobility induced by NEDD4 overexpression. Furthermore, we confirmed that NEDD4 induced the degradation of HBx in a ubiquitin/proteasome-dependent manner via K48-linked ubiquitination. Our findings suggest that NEDD4 exerts a tumor-suppressive effect in HBV-associated HCC by acting as an E3 ubiquitin ligase for HBx degradation and provide new insights into the function of NEDD4.

TIGIT/PVR and LncRNA ANRIL dual-targetable PAMAM polymeric nanoparticles efficiently inhibited the hepatoma carcinoma by combination of immunotherapy and gene therapy.

Herein, a novel polymeric nanoparticle was designed to inhibit hepatoma carcinoma by simultaneously targeting the T cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor (PVR) and long noncoding RNAs antisense noncoding RNA in the INK4 locus (LncRNA ANRIL). Firstly, the siANRIL-loaded nanoparticles (NP-siANRIL) was developed by methoxy-poly (ethylene glycol)-polyamidoamine (mPEG-PAMAM) and polyamidoamine-poly (ethylene glycol)-disulphide bond-carboxyl (PAMAM-PEG-S2-COOH) using the self-assembly method. Then the DTBP-3 peptide, a newly developed identified peptide which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR, was further conjugated on the surface of NP-siANRIL via the glutathione (GSH)-sensitive disulphide linkage. In this way, the binding ability of DTBP-3 to TIGIT was remained once they were entrapped into the tumour tissues which were abundant of GSH. The present study demonstrated that DTBP-3NP-siANRIL exhibited an excellent anti-tumour effect on hepatoma carcinoma in vivo by simultaneously inhibited the expression of miR-203a and its downstream genes and increased the percentages of NK cells and T cells. In a word, the present study has presented a novel strategy for treatment of hepatoma carcinoma by simultaneously targeting of TIGIT/PVR and LncRNA ANRIL.

An integrated space-to-ground quantum communication network over 4,600 kilometres.

Quantum key distribution (QKD)1,2 has the potential to enable secure communication and information transfer3. In the laboratory, the feasibility of point-to-point QKD is evident from the early proof-of-concept demonstration in the laboratory over 32 centimetres4; this distance was later extended to the 100-kilometre scale5,6 with decoy-state QKD and more recently to the 500-kilometre scale7-10 with measurement-device-independent QKD. Several small-scale QKD networks have also been tested outside the laboratory11-14. However, a global QKD network requires a practically (not just theoretically) secure and reliable QKD network that can be used by a large number of users distributed over a wide area15. Quantum repeaters16,17 could in principle provide a viable option for such a global network, but they cannot be deployed using current technology18. Here we demonstrate an integrated space-to-ground quantum communication network that combines a large-scale fibre network of more than 700 fibre QKD links and two high-speed satellite-to-ground free-space QKD links. Using a trusted relay structure, the fibre network on the ground covers more than 2,000 kilometres, provides practical security against the imperfections of realistic devices, and maintains long-term reliability and stability. The satellite-to-ground QKD achieves an average secret-key rate of 47.8 kilobits per second for a typical satellite pass-more than 40 times higher than achieved previously. Moreover, its channel loss is comparable to that between a geostationary satellite and the ground, making the construction of more versatile and ultralong quantum links via geosynchronous satellites feasible. Finally, by integrating the fibre and free-space QKD links, the QKD network is extended to a remote node more than 2,600 kilometres away, enabling any user in the network to communicate with any other, up to a total distance of 4,600 kilometres.

Security of a kind of quantum secret sharing with entangled states.

We present a new collusion attack to a kind of quantum secret sharing schemes with entangled states. Using this attack, an unauthorized set of agents can gain access to the shared secret without the others' cooperation. Furthermore, we establish a general model for this kind of quantum secret sharing schemes and then give some necessary conditions to design a secure quantum secret sharing scheme under this model.

Entanglement concentration for arbitrary four-particle linear cluster states.

Cluster states, whose model are a remarkably rich structure in measurement-based quantum computation, hold high degree of entanglement, while entanglement is very fragile during the process of transmission because of the inevitable interaction with the environment. We propose two entanglement concentration protocols for four-particle linear cluster states which and are susceptible to the decoherence and the imperfect communication setups. In the first protocol, POVM operators are introduced to maximize the success probability, and the second protocol is based on cross-Kerr nonlinearity which is utilized to check the parity between the original particle and the ancillary particle. Both of the protocols have their own advantages. The first one can be easily realized in experiment by linear optics, while the one with cross-Kerr nonlinearity reach more than 90% success probability by iteration. Since the wide application of cluster states, the two protocols are efficient and valuable to different fields of quantum communication.

Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System.

Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 µg/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests. Furthermore, ginsenoside Rg1 treatment prevented LPS-induced decrease of acetylcholine (ACh) levels and increase of acetylcholinesterase (AChE) activity. Ginsenoside Rg1 treatment also reverted the decrease of alpha7 nicotinic acetylcholine receptor (α7 nAChR) protein expression in the prefrontal cortex (PFC) and hippocampus of LPS-treated rats. These findings suggest that ginsenoside Rg1 has protective effect against LPS-induced cognitive deficit and that prevention of LPS-induced changes in cholinergic system is crucial to this ameliorating effect.

Security of quantum digital signatures for classical messages.

Quantum digital signatures can be used to authenticate classical messages in an information-theoretically secure way. Previously, a novel quantum digital signature for classical messages has been proposed and gave an experimental demonstration of distributing quantum digital signatures from one sender to two receivers. Some improvement versions were subsequently presented, which made it more feasible with present technology. These proposals for quantum digital signatures are basic building blocks which only deal with the problem of sending single bit messages while no-forging and non-repudiation are guaranteed. For a multi-bit message, it is only mentioned that the basic building blocks must be iterated, but the iteration of the basic building block still does not suffice to define the entire protocol. In this paper, we show that it is necessary to define the entire protocol because some attacks will arise if these building blocks are used in a naive way of iteration. Therefore, we give a way of defining an entire protocol to deal with the problem of sending multi-bit messages based on the basic building blocks and analyse its security.

Practical quantum private query of blocks based on unbalanced-state Bennett-Brassard-1984 quantum-key-distribution protocol.

Until now, the only kind of practical quantum private query (QPQ), quantum-key-distribution (QKD)-based QPQ, focuses on the retrieval of a single bit. In fact, meaningful message is generally composed of multiple adjacent bits (i.e., a multi-bit block). To obtain a message a1a2···al from database, the user Alice has to query l times to get each ai. In this condition, the server Bob could gain Alice's privacy once he obtains the address she queried in any of the l queries, since each a(i) contributes to the message Alice retrieves. Apparently, the longer the retrieved message is, the worse the user privacy becomes. To solve this problem, via an unbalanced-state technique and based on a variant of multi-level BB84 protocol, we present a protocol for QPQ of blocks, which allows the user to retrieve a multi-bit block from database in one query. Our protocol is somewhat like the high-dimension version of the first QKD-based QPQ protocol proposed by Jacobi et al., but some nontrivial modifications are necessary.