The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and ...may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.
•A sustainable and eco-friendly CFP-based TENG is fabricated.•The CFP-based TENG can be dispersed in DI water within 30 min by sonicating.•The CFP-based TENG can power small electronic devices.•The ...CFP-based TENG can be used in self-powered human–machine interactive systems.
Global warming and other world climate issues have spawned extensive research on the green, recyclable and biodegradable distributed energy harvesting triboelectric nanogenerator (TENG) for the collection of renewable energy. Cellulose filter paper (CFP), as a biocompatible natural material with a unique three-dimensional porous network structure, high crystallinity and excellent mechanical flexibility, can be used to create biodegradable and environmentally friendly TENGs. Here, we have developed a green and recyclable CFP-based energy harvesting and human–computer interaction system based on the single-electrode structure. It is composed of PVDF-coated CFP and conductive Cu-coated CFP as friction layer and electrode respectively. The degradation experiment verified the composite film materials can be completely dispersed and dissolved in deionized (DI) water in 30 min using an ultrasonic instrument, which fully proves the green and environmental protection of the prepared CFP-based TENG. We also thoroughly studied the output properties of the fabricated CFP-based TENGs, which demonstrates a maximum output voltage of 192 V, output current of 9.3μA, and output power at736.7 mW m−2. The CFP-based TENGs can be conveniently adopted to power commercial electronic products and as a wearable interface to control computer programs. This research demonstrates the effective way to develop CFP-based TENG for energy collecting and human–computer interaction devices with high biodegradability, which is important for realizing the environmental protection of electronic equipment, promoting energy conservation and emission reduction, and achieving carbon neutrality.
Circular RNAs (circRNAs) play important regulatory roles in the development of various cancers. However, biological functions and the underlying molecular mechanism of circRNAs in gastric cancer (GC) ...remain obscure.
Differentially expressed circRNAs were identified by RNA sequencing. The biological functions of circSHKBP1 in GC were investigated by a series of in vitro and in vivo experiments. The expression of circSHKBP1 was evaluated using quantitative real-time PCR and RNA in situ hybridization, and the molecular mechanism of circSHKBP1 was demonstrated by western blot, RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Lastly, mouse xenograft and bioluminescence imaging were used to exam the clinical relevance of circSHKBP1 in vivo.
Increased expression of circSHKBP1(hsa_circ_0000936) was revealed in GC tissues and serum and was related to advanced TNM stage and poor survival. The level of exosomal circSHKBP1 significantly decreased after gastrectomy. Overexpression of circSHKBP1 promoted GC cell proliferation, migration, invasion and angiogenesis in vitro and in vivo, while suppression of circSHKBP1 plays the opposite role. Exosomes with upregulated circSHKBP1 promoted cocultured cells growth. Mechanistically, circSHKBP1 sponged miR-582-3p to increase HUR expression, enhancing VEGF mRNA stability. Moreover, circSHKBP1 directly bound to HSP90 and obstructed the interaction of STUB1 with HSP90, inhibiting the ubiquitination of HSP90, resulting in accelerated GC development in vitro and in vivo.
Our findings demonstrate that exosomal circSHKBP1 regulates the miR-582-3p/HUR/VEGF pathway, suppresses HSP90 degradation, and promotes GC progression. circSHKBP1 is a promising circulating biomarker for GC diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.
Nowadays, with the intensification of the aging society, the demand for elderly care and medical services is increasing and the elderly care and health systems are facing serious challenges. ...Therefore, it is imperative to develop a smart elderly care system to achieve real-time interaction between the elderly, the community, and medical personnel and to improve the efficiency of caring for the elderly. Here, we prepared ionic hydrogels with stable properties of high mechanical strength, high electrical conductivity, and high transparency by the one-step immersion method and used them in self-powered sensors for smart elderly care systems. The complexation of Cu
ions with polyacrylamide (PAAm) endows ionic hydrogels with excellent mechanical properties and electrical conductivity. Meanwhile, potassium sodium tartrate prevents the generated complex ions from precipitating into precipitates, thus ensuring the transparency of the ionic conductive hydrogel. After optimization, the transparency, tensile strength, elongation at break, and conductivity of the ionic hydrogel reached 94.1% at 445 nm, 192 kPa, 1130%, and 6.25 S/m, respectively. By processing and coding the collected triboelectric signals, a self-powered human-machine interaction system attached to the finger of the elderly was developed. The elderly can complete the transmission of distress and basic needs by simply bending their fingers, greatly reducing the pressure of inadequate medical care in an aging society. This work demonstrates the value of self-powered sensors in the field of smart elderly care systems, showing a wide implication in human-computer interface.
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•Circulating tumor cells are pro-metastasis precursors.•Heterogeneity of circulating tumor cells associated with breast cancer progression.•Genetic properties of circulating tumor ...cells affect distant metastases.•Components secreted by tumor microenvironment guide circulating tumor cells to specific metastatic sites.
Circulating tumor cells (CTCs) are viewed as pro-metastasis precursors shed from primary tumors or metastatic sites. The phenotypic and molecular heterogeneity of CTCs is associated with breast cancer progression and prognosis. Therefore, we divided CTCs into several subtypes according to their differences in biomarker status, epithelial/mesenchymal phenotype, aggregation status, and other factors to summarize their characteristics. Considering that the organ-specific metastasis is a hallmark of breast cancer, we adopted the “seed and soil” model to further analyze the relationship between the heterogeneity of CTCs and the organotropism of breast cancer. We speculated that CTCs might not only develop their genetic potential but communicate with surroundings, including chemokine systems, hemocytes, and extracellular matrix components, to regulate the organ-specific metastases of breast cancer.
Triboelectric nanogenerators (TENGs) are widely used in self‐powered electronic devices and tactile sensors. Herein, for the first time, the facile, low‐cost, and universal electroless deposition ...(ELD) technology is used to fabricate nonconductive black Cu to enhance the electrical output performance and sensitivities of TENG‐based tactile sensor. The output performance and sensitivities of the equipment are significantly improved by the introduction of black Cu nanoparticles (NPs) coated cellulose filter paper (CFP) into the polydimethylsiloxane (PDMS) matrix. With an optimal load of black Cu NPs, the composite film‐based TENG produces the highest surface charge density exhibited by high sensitivities of 1.56 V N−1, 3.5 times of that obtained via PDMS‐based TENG under the same conditions. These properties facilitate the developed device to be competent at monitoring a kind of human movements, such as finger touching and bending. The proposed strategy not only demonstrates a promising potential of developing large‐scale practical self‐charging equipment and improving the output performance and sensitivities of TENG based tactile sensors but also provides a new perspective for applications in other fields.
Herein, facile, low‐cost, and universal electroless deposition (ELD) technology is used in a new way to fabricate nonconductive black Cu to improve the output performance and sensitivities of triboelectric nanogenerator (TENG)‐based tactile sensors. Moreover, a self‐charging tactile sensor based on the improved TENG is demonstrated, which exhibits high sensitivity and good linear correlation.
The ubiquitous presence of inorganic and organic phosphorus in wastewater and natural water bodies has deteriorated the water environment qualities and exerted significant influences on ecosystems. ...In this study, an effective polypyrrole modified red mud adsorbent (PRM) was optimized for the adsorptive removal of inorganic and organic phosphorus from aqueous solutions. The addition of ferric chloride and pyrrole was optimized for complete oxidation and modification of polypyrrole onto red mud. Kinetic studies illustrated that the adsorption progress was accomplished by physical and chemical adsorption. The experimental data of the optimized PRM were described well by Langmuir isotherm, and the equilibrium adsorption capacity was 32.9 and 54.7 mg/g for inorganic and organic phosphorus, respectively. The PRM showed commendable adsorption performance despite the pH conditions ranging from 3 to 11. From the effect of ion strength and X-ray photoelectron spectroscopy (XPS) tests, we found that ligand exchange is the main mechanism of orthophosphate adsorption onto PRM, while electrostatic attraction played an important role in organic phosphorus adsorption. The adsorption performance from column studies showed that the velocity of flow influenced the breakthrough time of the column but the initial concentration had minor impacts. This study would extend the potential application of polypyrrole modified red mud, acting as an efficient adsorbent for inorganic and organic phosphorus adsorption in water treatment.
•Inorganic and organic phosphorus adsorption onto PRM was investigated.•The proper synthesis of polypyrrole onto red mud was optimized.•Different adsorption mechanisms of inorganic and organic phosphate were proposed.
Piwi-interacting RNAs (piRNAs) are a novel type of small noncoding RNAs, which are 26–30 nt in length and bind to Piwi proteins. These short RNAs were originally discovered in germline cells and are ...considered as key regulators for germline maintenance. A growing body of evidence has now extended our views into piRNA biological significance showing that they can also regulate gene expression in somatic cells through transposon silencing, epigenetic programming, DNA rearrangements, mRNA turnover, and translational control. Mounting studies have revealed that the dysregulation of piRNAs may cause epigenetic changes and contribute to diverse diseases. This review illustrates piRNA biogenesis, mechanisms behind piRNA-mediated gene regulation, and changes of piRNAs in different diseases, especially in cancers.
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Shu and colleagues demonstrate the biogenesis, functions, changes, and probable roles of piRNAs in diseases of different systems, especially in cancers. piRNAs are promising novel biomarkers for early diagnosis and therapeutic targets for precise medicine.
•A new BN model for risk assessment was developed.•The BN model is based on CM, IT2FSs, and the improved D-S evidence theory.•A new BPA function and a new evidence fusion rule algorithm were ...defined.•D-S evidence theory was improved under the IT2FSs environment.•The BN model could be used to predict the risk and analyze the sensitivity.
Traditional Bayesian network (BN) model is established by crisp sets and probabilities, and its effectiveness and applicability are restricted. In order to solve this problem, a new BN model for risk assessment based on cloud model (CM), interval type-2 fuzzy sets (IT2FSs) and the improved Dempster-Shafer (D-S) evidence theory was developed in the following route. Firstly, CM and IT2FSs were used to define a new solution for the digital characteristics, and the standard and index cloud membership functions for the IT2FSs-CM were established. Then, the index cloud membership function for the IT2FSs-CM was defined as the basic probability assignment (BPA) function, a new evidence fusion rule algorithm was defined, and the improved D-S evidence theory was proposed. Furthermore, the improved D-S evidence theory was used to transform the BPA function into the IT2FSs based prior probability, and a new BN model for risk assessment was developed. Finally, the BN model was applied to a nuclear power plant (NPP) construction project, its risk was assessed at level I (very low risk), and the results by IT2FSs-CM and Bayesian reasoning were compared with those by common methods. The findings show that the new BN model is effective and applicable in risk assessment.
Lactate accumulation in the tumor microenvironment was shown to be closely related to tumor growth and immune escape, and suppression of lactate production by inhibiting lactate dehydrogenase A ...(LDHA) has been pursued as a potential novel antitumor strategy. However, only a few potent LDHA inhibitors have been developed and most of them did not show potent antitumor effects in vivo. To this end, we designed new LDHA inhibitors and obtained a novel potent LDHA inhibitor, ML‐05. ML‐05 inhibited cellular lactate production and tumor cell proliferation, which was associated with inhibition of ATP production and induction of reactive oxygen species and G1 phase arrest. In a mouse B16F10 melanoma model, intratumoral injection of ML‐05 significantly reduced lactate production, inhibited tumor growth, and released antitumor immune response of T cell subsets (Th1 and GMZB+CD8 T cells) in the tumor microenvironment. Moreover, ML‐05 treatment combined with programmed cell death‐1 Ab or stimulator of interferon genes protein (STING) could sensitize the antitumor activity in B16F10 melanoma model. Collectively, we developed a novel potent LDHA inhibitor, ML‐05, that elicited profound antitumor activity when injected locally, and was associated with the activation of antitumor immunity. In addition, ML‐05 could sensitize immunotherapies, which suggests great translational value.
The novel LDHA inhibitor, ML‐05, reduces lactic acid in the tumor microenvironment, releases T‐cell function, and enhances immunotherapy with great translational value.
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