Explore the vast range of titles available.

Micro-nano biorobots based on bacteria have demonstrated great potential for tumor diagnosis and treatment. The bacterial gene expression and drug release should be spatiotemporally controlled to avoid drug release in healthy tissues and undesired toxicity. Herein, we describe an alternating magnetic field-manipulated tumor-homing bacteria developed by genetically modifying engineered Escherichia coli with Fe 3 O 4 @lipid nanocomposites. After accumulating in orthotopic colon tumors in female mice, the paramagnetic Fe 3 O 4 nanoparticles enable the engineered bacteria to receive and convert magnetic signals into heat, thereby initiating expression of lysis proteins under the control of a heat-sensitive promoter. The engineered bacteria then lyse, releasing its anti-CD47 nanobody cargo, that is pre-expressed and within the bacteria. The robust immunogenicity of bacterial lysate cooperates with anti-CD47 nanobody to activate both innate and adaptive immune responses, generating robust antitumor effects against not only orthotopic colon tumors but also distal tumors in female mice. The magnetically engineered bacteria also enable the constant magnetic field-controlled motion for enhanced tumor targeting and increased therapeutic efficacy. Thus, the gene expression and drug release behavior of tumor-homing bacteria can be spatiotemporally manipulated in vivo by a magnetic field, achieving tumor-specific CD47 blockage and precision tumor immunotherapy. Several strategies have been employed to enhance the tumor-targeting and anti-cancer properties of engineered bacteria. Here the authors describe the design of alternating magnetic field-manipulated bacteria engineered to release an anti-CD47 nanobody, promoting anti-tumor immune response in preclinical cancer models.

Electric stimulation has been used in changing the morphology, status, membrane permeability, and life cycle of cells to treat certain diseases such as trauma, degenerative disease, tumor, and infection. To minimize the side effects of invasive electric stimulation, recent studies attempt to apply ultrasound to control the piezoelectric effect of nano piezoelectric material. This method not only generates an electric field but also utilizes the benefits of ultrasound such as non-invasive and mechanical effects. In this review, important elements in the system, piezoelectricity nanomaterial and ultrasound, are first analyzed. Then, we summarize recent studies categorized into five kinds, nervous system diseases treatment, musculoskeletal tissues treatment, cancer treatment, anti-bacteria therapy, and others, to prove two main mechanics under activated piezoelectricity: one is biological change on a cellular level, the other is a piezo-chemical reaction. However, there are still technical problems to be solved and regulation processes to be completed before widespread use. The core problems include how to accurately measure piezoelectricity properties, how to concisely control electricity release through complex energy transfer processes, and a deeper understanding of related bioeffects. If these problems are conquered in the future, piezoelectric nanomaterials activated by ultrasound will provide a new pathway and realize application in disease treatment.

The spread of antibiotic resistance genes (ARGs) poses a substantial threat to human health. Phage-mediated transduction could exacerbate ARG transmission. While several case studies exist, it is yet unclear to what extent phages encode and mobilize ARGs at the global scale and whether human impacts play a role in this across different habitats. Here, we combine 38,605 bacterial genomes, 1432 metagenomes, and 1186 metatranscriptomes across 12 contrasting habitats to explore the distribution of prophages and their cargo ARGs in natural and human-impacted environments. Worldwide, we observe a significant increase in the abundance, diversity, and activity of prophage-encoded ARGs in human-impacted habitats linked with relatively higher risk of past antibiotic exposure. This effect was driven by phage-encoded cargo ARGs that could be mobilized to provide increased resistance in heterologous E. coli host for a subset of analyzed strains. Our findings suggest that human activities have altered bacteria-phage interactions, enriching ARGs in prophages and making ARGs more mobile across habitats globally. Antibiotic resistance genes pose a serious threat to human health, yet the impact of phages on these genes’ transmission in bacterial communities is not well understood. In this study, the authors show that human activities accelerate the movement of phage-encoded antibiotic-resistance genes between habitats.

Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that eventually leads to disability. Inflammatory cell infiltration, severe joint breaking and systemic bone loss are the main clinical symptoms. In this study, we established a collagen-induced arthritis (CIA) model and found a large number of M1 macrophages and pyroptosis, which are important sources of proinflammatory cytokines. Punicalagin (PUN) is an active substance extracted from pomegranate peel. We found that it inhibited joint inflammation, cartilage damage and systemic bone destruction in CIA mice. PUN effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo . PUN treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide (LPS) and interferon (IFN)-γ. The expression of inducible nitric oxide synthase (iNOS) and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment group. However, simultaneously, the expression of markers of anti-inflammatory M2 macrophages, such as arginase (Arg)-1 and interleukin (IL)-10, was increased. In addition, PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1, thereby preventing inflammatory cell death resulting from the release of IL-1β and IL-18. Mechanistically, PUN inhibited the activation of receptor activators of the nuclear factor-κB (NF-κB) signaling pathway, which contributes to M1 polarization and pyroptosis of macrophages. We concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA.

Chronic disease incidence among the elderly is increasing, which is correlated with the acceleration of population aging. Evolving internet technologies may help prevent and provide interventions for chronic diseases in an accelerating aging process. However, the impact of daily internet use on the incidence of chronic diseases is not well understood. This study aims to investigate whether daily internet use by middle-aged and older adults may inhibit or promote the occurrence of chronic diseases. We included participants from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal survey of Chinese residents aged ≥45 years. We assessed 8-year data from wave 1 (June 2011-March 2012) to wave 4 (July-September 2018) in CHARLS. Data from wave 4 were used for a cross-sectional study, and data from all 4 waves were used for a longitudinal study. Self-reported data were used to track variables, including internet use, use frequency, and the incidence of different chronic diseases. Cox proportional hazards modeling was applied in the longitudinal study to examine the relationship between daily internet use and chronic diseases among middle-aged and older adults, while adjusting for sociodemographic characteristics and health behaviors. In addition, longitudinal data were used to analyze internet usage trends, and cross-sectional data were used to analyze the factors influencing internet use. Among the 20,113 participants included in the longitudinal analyses, internet use increased significantly, from 2% to 12.3%, between 2011 and 2018. The adjusted model found statistically significant relationships between daily internet use and a lower incidence of the following chronic diseases: hypertension (hazard ratio [HR] 0.78, 95% CI 0.65-0.95, P=.01), chronic lung disease (HR 0.74, 95% CI 0.57-0.97, P=.03), stroke (HR 0.69, 95% CI 0.50-0.94, P=.02), digestive disease (HR 0.73, 95% CI 0.58-0.91, P=.005), memory-related disorders (HR 0.58, 95% CI 0.37-0.91, P=.02), arthritis or rheumatism (HR 0.60, 95% CI 0.48-0.76, P<.001), asthma (HR 0.52, 95% CI 0.33-0.84, P=.007), depression (HR 0.80, 95% CI 0.71-0.89, P<.001), and vision impairment (HR 0.83, 95% CI 0.74-0.93, P=.004). Moreover, our study also showed that with increasing frequency of internet use, the risk of some chronic diseases decreases. This study found that middle-aged and older adults who use the internet have a reduced risk of developing chronic diseases versus those who do not use the internet. The increasing prevalence of daily internet use among middle-aged and older adults may stimulate contemplation of the potential role of internet platforms in future research on chronic disease prevention.

Electrochemical nitrate reduction in alkaline media offers a sustainable route for ammonia synthesis at rates rivaling those of the Haber–Bosch process. However, its energy efficiency is limited by sluggish nitrate deoxidation and hydrogenation, compounded by challenges in proton supply via H 2 O dissociation. Here, we develop an enzyme-like substrate transport channel through a hierarchical arrangement of metallic Ag and Ru nanophases, to enable cascade nitrate-to-ammonia conversion and optimize underpotential-deposited hydrogen utilization. Operando characterization and theoretical calculations reveal that Ag–Ru electronic synergy regulates underpotential-deposited hydrogen coverage at Ru-centered active sites by coupling facilitated H 2 O dissociation with *OH-mediated site regeneration, thereby promoting nitrite relay conversion. Our underpotential-deposited hydrogen-assisted nitrate electroreduction system delivers a half-cell ammonia energy efficiency of 53.7% at 0.2 V versus RHE with near-unity Faradaic efficiency across a wide nitrate concentration range, and an ammonia partial current density of 2.2 A cm −2 at 0 V versus RHE. Pairing cathodic nitrate reduction with anodic H 2 oxidation enables ammonia production costs below $1.15 kg −1 while maintaining sustained energy efficiency over 100 h at 200 mA cm −2 . Electrochemical nitrate reduction rivals Haber-Bosch ammonia synthesis rates but suffers from poor energy efficiency. Here, the authors show that underpotential deposited hydrogen can be unlocked to accelerate nitrate conversion, offering an pathway to energy-efficient ammonia production.

Gadolinium (Gd 3+ )-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks “Gd-Tex-lipids” to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O 2 concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd 3+ , the versatile Mb@Gd-NTs can also chelate 177 Lu 3+ (Mb@ 177 Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This “one-for-all” nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy. Researchers have been working on radiosensitizers to improve radiotherapy efficacy. Here the authors generate gadolinium nanotexaphyrins (Gd-NTs) that self-assemble and further load it with myoglobulin to relieve hypoxia, improve radiosensitization effects of Gd-coordinated Texaphyrin, and suppress tumor recurrence.

The limited efficacy of radiotherapy leads to radio‐resistance and high rates of tumor recurrence and metastasis, which is caused by tumor hypoxia, rapid DNA damage repair, and especially the suppressive immune microenvironment of tumor. Lots of immune cell‐derived exosomes can regulate antitumor immunity, but their application in enhancing radiotherapy is rarely studied. Herein, as a model of concept, M1 macrophage‐derived exosomes (M1Exos) is engineered as effective radiotherapy sensitizers, realizing the trilogy of radiotherapy sensitization: 1) M1Exos is engineered to express catalases on the inside of membrane, which can effectively relieve tumor hypoxia, and enhance DNA damage. 2) The DNA damage repair inhibitor is loaded in M1Exos to effectively inhibit DNA damage repair. 3) M1Exos can polarize M2 macrophages into M1 phenotypes, and the anti‐PD‐L1 nanobody engineered on the outside of M1Exos can relieve the immunosuppression of T cells, both ultimately leading to the remodeling of the tumor suppressive microenvironment. The trilogy of radiotherapy sensitization achieves excellent antitumor efficacy, exhibiting the good utility of engineering immune cell‐derived exosomes as radiotherapy sensitizers, inspiring the future efforts to explore different kinds of immune cell‐derived exosomes for enhanced radiotherapy. M1 macrophage‐derived exosomes with catalase (CAT) and anti‐PD‐L1 (programmed death ligand‐1) nanobody expressed on membrane and DNA damage repair inhibitor (DDRi) encapsulated inside is engineered as effective radiotherapy sensitizers, realizing the trilogy of radiotherapy sensitization: the relief of tumor hypoxia, the inhibition of DNA damage repair, and the remodeling of tumor suppressive immune microenvironment. This work exhibits the good utility of engineering immune cell‐derived exosomes as effective radiotherapy sensitizers.

PurposeThe complete ammonia oxidizers (comammox) capable of catalyzing nitrification, oxidizing ammonia to nitrate, via activity of only one type of microbes were recently discovered which has updated our knowledge of traditional two-step nitrification. The extent of contribution of comammox and canonical ammonia oxidizers including ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) to soil nitrification, especially in soils with long-term input of nitrogen (N) fertilizers, remains unknown.Materials and methodsThe transcriptional abundance of amoA gene from comammox, AOA, and AOB in soils fertilized for 29 years was investigated in different seasons and soil layers via quantitative PCR.Results and discussionThe results showed that comammox were detected in all soil samples; however, AOA and AOB had significantly higher transcriptional abundance of amoA gene than comammox. Nitrification activity was most significantly correlated with the transcriptional abundance of AOA amoA gene (Pearson correlation, r = 0.217, P < 0.05) suggesting AOA were the dominant contributors to soil potential nitrification. Lower abundances of amoA gene transcripts were observed in July than in April and November. The application of high level of mineral N fertilizer decreased the abundance of both AOA and AOB; however, long-term input of organic manure combined with mineral N fertilizer stabilized the abundances of ammonium-oxidizing microbes in soils. Seasonal variation and fertilization regimes substantially affected the abundance of both AOA and AOB, but AOB were not as sensitive in responding to the seasonal variation and fertilization as AOA. The analysis of RDA and VPA demonstrated that sampling month, soil depth, and fertilization regime explained 30.20%, 11.46%, and 5.40% of the variation in nitrification microorganism amoA gene composition, respectively. Seasonal variation exerted the most influences on the nitrifiers’ composition, and soil depth and fertilization regime were also important factors in shaping the nitrifier communities. According to the correlation analysis, NO3−–N content was the most important soil property in impacting the transcriptional abundance of amoA gene, and the amoA gene transcript abundance decreased with increasing NO3−–N content.ConclusionsThe results suggest that the activity of comammox may be more inhibited by the long-term nitrogen fertilization than canonical ammonia oxidizers in agricultural soils. This study provides insights into the different responses of comammox and canonical ammonia oxidizers to fertilization, seasonal variation, and soil depth and their relative contributions to nitrification in agricultural soil.