Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Cation/Anion-Dual regulation in Na3MnTi(PO4)3 cathode achieves the enhanced electrochemical properties of Sodium-Ion batteries.

Na3MnTi(PO4)3 (NMTP) emerges as a promising cathode material with high-performance for sodium-ion batteries (SIBs). Nevertheless, its development has been limited by several challenges, including poor electronic conductivity, the Mn3+ Jahn-Teller effect, and the presence of a Na+/Mn2+ cation mixture. To address these issues, we have developed a cation/anion-dual regulation strategy to activate the redox reactions involving manganese, thereby significantly enhancing the performance of NMTP. This strategy simultaneously enhances the structural dynamics and facilitates rapid ion transport at high rates by inducing the formation of sodium vacancy. The combined effects of these modifications lead to a substantial improvement in specific capacity (79.1 mAh/g), outstanding high-rate capabilities (35.9 mAh/g at 10C), and an ultralong cycle life (only 0.040 % capacity attenuation per cycle over 250 cycles at 1C for Na3.34Mn1.2Ti0.8(PO3.98F0.02)3) when used as a cathode material in SIBs. Furthermore, its performance in full cell demonstrates impressive rate capability (44.4 mAh/g at 5C) and exceptional cycling stability (with only 0.116 % capacity decay per cycle after 150 cycles at 1C), suggesting its potential for practical applications. This work presents a dual regulation strategy targeting different sites, offering a significant advancement in the development of NASICON phosphate cathodes for SIBs.

Entropy-Regulated Cathode with Low Strain and Constraint Phase-Change Toward Ultralong-Life Aqueous Al-Ion Batteries.

During multivalent ions insertion processes, intense electrostatic interaction between charge carriers and host makes the high-performance reversible Al3+ storage remains an elusive target. On account of the strong electrostatic repulsion and poor robustness, Prussian Blue analogues (PBAs) suffer severely from the inevitable and large strain and phase change during reversible Al3+ insertion. Herein, we demonstrate an entropy-driven strategy to realize ultralong life aqueous Al-ion batteries (AIBs) based on medium entropy PBAs (ME-PBAs) host. By multiple redox active centers introduction, the intrinsic poor conductivity can be enhanced simultaneously, resulting in outstanding capabilities of electrochemical Al3+ storage. Meanwhile, the co-occupation at metal sites in PBA frameworks can also increase the M-N bond intensity, which is beneficial for constraining the phase change during consecutive Al3+ reversible insertion, to realize an extended lifespan over 10,000 cycles. Based on the calculation at different operation states, the fluctuation of ME-PBA lattice parameters is only 1.2 %. Assembled with MoO3 anodes, the full cells can also deliver outstanding electrochemical properties. The findings highlight that, the entropy regulation strategy could uncover the isochronous constraint on both strain and phase transition for long-term reversible Al3+ storage, providing a promising design for advanced electrode materials for aqueous multivalent ions batteries.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Tuning oxygen release of sodium-ion layered oxide cathode through synergistic surface coating and doping.

Layered transition metal oxides have the greatest potential for commercial application as cathode materials for sodium-ion batteries. However, transition metal oxides inevitably undergo an irreversible oxygen loss process during cycling, which leads to structural changes in the material and ultimately to severe capacity degradation. In this work, using density function theory (DFT) calculations, the Ni-O bond is revealed to be the weakest of the M-O bonds, which may lead to structural failure. Herein, the synergistic surface CeO2 modification and the trace doping of Ce elements stimulate oxygen redox and improve its reversibility, thus improving the structural stability and electrochemical performance of the material. Theoretical calculations prove that Na0.67Mn0.7Ni0.2Co0.1O2 (MNC) obtains electrons from CeO2, avoiding destruction of the Ni-O bond by over-energy released during the charging process and inhibiting oxygen loss. The capacity retention was 77.37% for 200 cycles at 500 mA g-1, compared to 33.84% for the unmodified Na0.67Mn0.7Ni0.2Co0.1O2. Overall, the present work demonstrates that the synergistic effect of surface coating and doping is an effective strategy for realizing tuning oxygen release and high electrochemical performance.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. METHODS: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. FINDINGS: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). INTERPRETATION: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. FUNDING: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Gibberellic acid alleviates cadmium toxicity in rice by regulating NO accumulation and cell wall fixation capacity of cadmium.

Gibberellic acid (GA) has been implicated in the response of plants to cadmium (Cd) stress, but the underlying mechanism remains unclear. In the present study, our aim was to confirm the role of GA in regulating the accumulation of Cd in rice. We found that Cd stress elevated the endogenous GA level in the rice roots. Exogenous GA application not only decreased the fixation of Cd in the root cell wall through reducing the hemicelluloses content, but also decreased the expression of OsNRAMP5 (Natural Resistance-Associated Macrophage Protein 5) and OsCd1 (a major facilitator superfamily gene). Both OsNRAMP5 and OsCd1 are related to Cd absorption, therefore, less Cd was accumulated in the roots. Furthermore, GA increased the expression of OsHMA3 (Heavy Metal ATPase 3) and OsCAL1 (Cadmium accumulation in Leaf 1), which are responsible for sequestering the Cd to the vacuoles and effluxing the Cd outside the cell, respectively, as a result, less Cd was accumulated in the shoots. In contrast, more Cd was accumulated in GA deficient lines. Furthermore, GA decreased the endogenous NO levels and the activity of antioxidant enzymes, while application of a NO scavenger-cPTIO diminished the alleviatory role of GA. In summary, the GA accelerated cell wall Cd exclusion mechanism probably improved rice tolerance to Cd toxicity via regulating the accumulation of NO.

MicroRNA­125a­mediated regulation of the mevalonate signaling pathway contributes to high glucose­induced proliferation and migration of vascular smooth muscle cells.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)­induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription­quantitative PCR results indicated that inhibition of miR­125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR­125a abrogated this effect. Furthermore, dual­luciferase reporter assay results identified that 3­hydroxy­3-methyglutaryl­coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR­125a. Moreover, HMGCR knockdown, similarly to miR­125a overexpression, suppressed HG­induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin­induced diabetes mellitus, it was demonstrated that miR­125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG­induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR­125a mimic. Therefore, the present results suggest that decreased miR­125a expression contributed to HG­induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR­125a­mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.

Ethical considerations of cellular immunotherapy for cancer.

With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.

Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury.

Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation.

Expression of serum sCD163 in patients with liver diseases and inflammatory disorders.

OBJECTIVE: To investigate the diagnostic values of soluble cluster of differentiation 163 (sCD163) in patients with liver failure or various inflammations. METHODS: Serum samples were collected from patients admitted to the First Affiliated Hospital, Zhejiang University from October 2013 to January 2015 for treatment of with liver diseases, including liver failure (n=38), hepatitis B virus (HBV)-induced liver cancer (HBsAg positive) (n=40), HBV-induced hepatic cirrhosis (HBsAg positive) (n=40), chronic hepatitis B (n=38), HBV carrier (n=40), fatty liver patients without HBV infection (n=40), chronic glomerulonephritis (n=38), community acquired pneumonia (n=38) and acute pancreatitis (n=38). The CD163/sCD163 was determined using commercial ELISA kits according to the manufacturer's instructions. RESULTS: Significant decrease was noticed in the sCD163 in patients with fatty liver and HBV carrier compared with that of patients with chronic hepatitis B (P < 0.05). Compared with the healthy controls, the level of sCD163 was remarkably increased in the other groups (P < 0.05). The serum sCD163 in patients with HBV-induced liver cancer showed statistical difference compared with those of the patients with fatty liver, HBV carrier, as well as those with liver failure (P < 0.05). The expression of sCD163 was remarkably elevated in patients with liver failure compared with the patients with liver cancer, HBV-induced hepatic cirrhosis, chronic hepatitis B, fatty liver, or HBV carrier (P < 0.05). No significant difference was noticed in the sCD163 in patients with chronic hepatitis B, community acquired pneumonia, chronic glomerulonephritis, and acute pancreatitis (P > 0.05). CONCLUSIONS: sCD163 is a sensitive marker protein for liver failure. The elevation of sCD163 was closely related to the progression of the liver failure. No statistical difference was noticed in the sCD163 in patients with inflammatory disorders, indicating sCD163 showed no organ specificity.

[Research advances on treatment of hepatitis C infection based on RNA interference and microRNA modulation].

Infection with hepatitis C virus (HCV) is one of the major global health problems, approximately 170 million people are infected worldwide. The chronic HCV infection is associated with a high risk of developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Unfortunately, there is still no effective vaccine or antibodies available for the prevention of infection. RNA interference (RNAi) represents a promising new approach to combat viral infections, and recent developments in the field of gene therapy have increased the feasibility of clinical applications. RNAi techniques have made rapid progress in the basic understanding of HCV biology and revealed numerous new viral and host-cell factors as potential targets for therapy. Together with the improvement of gene delivery technique and the discovery of the critical role of microRNA (miRNA) in HCV infection, RNAi and miRNA-based antiviral strategies hold great promise for the future. In this article, we provide a comprehensive overview of current developments of therapeutic targets of RNAi, liver-targeted delivery systems and the potential applications of miRNAs in treatment of hepatitis C infection.

[Drug delivery of CPC/amifostine/cisplatin complex in vitro and its ability in repairing bone defect and eliminating tumor in vivo].

OBJECTIVE: To investigate the feasibility of using calcium phosphate cement/amifostine/cisplatin complex to fill and repair bone defect, caused by tumor resection. METHODS: Drug concentration in the CPC/ amifostine/cisplatin complex was determined. Rabbits with bone defect and rats with osteosarcoma were implanted with CPC and CPC/amifostine/cisplatin complex. RESULTS: Similar bone growth was observed in the femurs of rabbits implanted with CPC/amifostine/cisplatin complex and those implanted with CPC. CPC/amifostine/cisplatin complex delivered amifostine and cisplatin consistently and eliminated osteosarcoma cells implanted in the rats. CONCLUSION: CPC/amifostine/cisplatin complex repairs bone defect caused by tumors as a filling material.

[Physicochemical and sustained drug release properties of calcium phosphate cement/amifostine/cisplatin complex and its effect in repairing bone defect due to tumor resection in rabbits].

OBJECTIVE: To investigate the feasibility of using calcium phosphate cement/amifostine complex as an new filling material for repairing bone defect caused by tumor resection. METHODS: Calcium phosphate cement (CPC)/cisplatin/amifostine complex was prepared at the mass ratio of 1000:2:5. The setting time, mechanical strength, and porosity of the complex were determined, and scanning electron microscopy and assessment of sustained drug release and inhibitory effect against osteosarcoma cells were carried out. The degradation of the material and new bone ingrowth were also observed in a rabbit model of femoral bone defect. RESULTS: The setting time, strength, and porosity, appearances under scanning electron microscope, and sustained drug release properties of CPC/cisplatin/amifostine complex were identical to those of CPC, and the integration of amifostine in the complex did not affect the cytotoxicity of cisplatin against the osteosarcoma cells. Pathological evidences of the degradation of the material and new bone ingrowth into the material were observed with the passage of time following its implantation into the bone defect in rabbits. CONCLUSION: The CPC/cisplatin/amifostine complex can be used as a filling material for repairing bone defect caused by tumor resection and eliminating the residual tumor cells in rabbits.

[Mice adipose derived Flk-1+ mesenchymal stem cells can ameliorate Duchenne's muscular dystrophy in Mdx mice for their multilineage potential].

Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. This study was purposed to investigate the feasibility to use adult adipose-derived mesenchymal stem cells (AD-MSCs) in the therapy of DMD. The Flk-1(+) MSCs were isolated from adipose tissue of adult GFP mice; the phenotype and cell cycle of MSCs were analyzed by flow cytometry; the AD-MSCs were directionally differentiated by myoblast and endotheliablast induction system in vitro and were identified by immumofluorecence staining and RT-PCR; the AD-MSCs were transplanted into CTX-injured mice model or mdx mice (DMD animal model) through tail vein; the distribution and differentiation of AD-MSCs were detected by immunofluorescence staining and RT-PCR respectively, and statistic analysis was performed. The results showed that the Flk-1(+) AD-MSCs could be induced to differentiate into myoblasts and endothelial cells in vitro. After transplanted into CTX-injured mice model or mdx mice, GFP-positive cells could be detected in damaged muscle, and these donor-derived cells were also positive for MHC, vWF, or Pax7. Flk-1(+) AD-MSC transplantation also partly reconstituted the expression of dystrophin, and reduced the percentage of centronucleated myofibers in mdx mice. It is concluded that Flk-1(+) AD-MSCs represent a possible tool for future cell therapy applications in DMD disease, as they can be delivered through the circulation for their potential of muscle homing. And Flk-1(+) AD-MSCs also show the ability to contribute to muscle repair, improvement of blood supply and long term reconstitution of dystrophy muscle.

[Potential of human adipose tissue derived adult stem cells differentiate into endothelial cells].

OBJECTIVE: To investigate whether human adipose derived adult stem (hADAS) cells can differentiate into endothelial cells. METHODS: Stem cells were isolated and expanded from adipose tissue and then induced to differentiate into cells of osteogenic, adipogenic and neurogenic lineages in vitro. hADAS cells were induced with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to endothelial cells differentiation. hADAS cells were intravenously injected into mouse hindlimb ischemic models to test their ability to differentiate endothelial cells in vivo. RESULTS: hADAS cells were easily isolated and expanded in vitro. They had the ability to differentiate into osteogenic, adipogenic and neurogenic lineages. The cells expressed vascular endothelial growth factor receptor-2 (VEGFR-2, Flk1), and expressed endothelial markers when cultured with VEGF and bFGF. In response to local cues, hADAS cells in vivo differentiate into endothelial cells that contributed to neoangiogenesis in hindlimb ischemia models. CONCLUSIONS: Flk1+ hADAS cells have multipotential not only similar to bone marrow mesenchymal stem cells, but also exhibiting characteristics of endothelial progenitor cells. They may be a potential source of endothelial cells for cellular pro-angiogenic therapies.