Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

High-frequency ultrasound imaging findings in the diagnosis of segmental schwannomatosis of the ulnar nerve: case report and literature review.

Schwannomatosis is characterized by the development of multiple schwannomas without evidence of vestibular tumors. Segmental schwannomatosis is defined as being limited to one limb or five or fewer contiguous segments of the spine. We report a case of a 20-year-old male with the painful masses of the left upper extremity with associated numbness and paresthesia in the ulnar nerve distribution. The high-frequency ultrasound showed that the ulnar nerve fascicles were enlarged and expanded with beadlike growth. The patient underwent surgery twice and all the tumors were pathologically confirmed to be schwannomas. Together, the medical history, imaging, and pathology findings indicated the diagnosis of segmental schwannomatosis. By the imaging diagnostic tools, MRI is the most commonly used in assistance with diagnosis of segmental schwannomatosis while high-frequency ultrasonography is rare. In this paper, we discuss the value of high-frequency ultrasonography in the diagnosis of this rare disease. This case report provides a deeper understanding of segmental schwannomatosis and may help improve the accuracy of preoperative diagnosis.

Identification and validation of a dysregulated TME-related gene signature for predicting prognosis, and immunological properties in bladder cancer.

Background: During tumor growth, tumor cells interact with their tumor microenvironment (TME) resulting in the development of heterogeneous tumors that promote tumor occurrence and progression. Recently, there has been extensive attention on TME as a possible therapeutic target for cancers. However, an accurate TME-related prediction model is urgently needed to aid in the assessment of patients' prognoses and therapeutic value, and to assist in clinical decision-making. As such, this study aimed to develop and validate a new prognostic model based on TME-associated genes for BC patients. Methods: Transcriptome data and clinical information for BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) and IMvigor210 databases, along with the MSigDB, were utilized to identify genes associated with TMEs (TMRGs). A consensus clustering approach was used to identify molecular clusters associated with TMEs. LASSO Cox regression analysis was conducted to establish a prognostic TMRG-related signature, with verifications being successfully conducted internally and externally. Gene ontology (GO), KEGG, and single-sample gene set enrichment analyses (ssGSEA) were performed to investigate the underlying mechanisms. The potential response to ICB therapy was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and Immunophenoscore (IPS). Additionally, it was found that the expression level of certain genes in the model was significantly correlated with objective responses to anti-PD-1 or anti-PD-L1 treatment in the IMvigor210, GSE111636, GSE176307, or Truce01 (registration number NCT04730219) cohorts. Finally, real-time PCR validation was performed on 10 paired tissue samples, and in vitro cytological experiments were also conducted on BC cell lines. Results: In BC patients, 133 genes differentially expressed that were associated with prognosis in TME. Consensus clustering analysis revealed three distinct clinicopathological characteristics and survival outcomes. A novel prognostic model based on nine TMRGs (including C3orf62, DPYSL2, GZMA, SERPINB3, RHCG, PTPRR, STMN3, TMPRSS4, COMP) was identified, and a TMEscore for OS prediction was constructed, with its reliable predictive performance in BC patients being validated. MultiCox analysis showed that the risk score was an independent prognostic factor. A nomogram was developed to facilitate the clinical viability of TMEscore. Based on GO and KEGG enrichment analyses, biological processes related to ECM and collagen binding were significantly enriched among high-risk individuals. In addition, the low-risk group, characterized by a higher number of infiltrating CD8+ T cells and a lower burden of tumor mutations, demonstrated a longer survival time. Our study also found that TMEscore correlated with drug susceptibility, immune cell infiltration, and the prediction of immunotherapy efficacy. Lastly, we identified SERPINB3 as significantly promoting BC cells migration and invasion through differential expression validation and in vitro phenotypic experiments. Conclusion: Our study developed a prognostic model based on nine TMRGs that accurately and stably predicted survival, guiding individual treatment for patients with BC, and providing new therapeutic strategies for the disease.

Food Security and Land Use under Sustainable Development Goals: Insights from Food Supply to Demand Side and Limited Arable Land in China.

The conflict between economic growth and the arable land demand poses a significant challenge to maintaining food security and achieving the Sustainable Development Goals. Meanwhile, substantial regional disparities in food consumption contribute to variations in land demand, further exacerbating constraints on food security. However, few studies have delved into regional differences in land demand related to food consumption. To bridge these gaps, this study estimated the arable land demand and associated pressures, considering food consumption patterns and the land footprint across 31 provincial districts in China. The findings reveal that grains remain the primary crop consumed by Chinese residents. Notably, the food consumption pattern exhibits substantial disparities among provincial districts, particularly concerning livestock products. Given China's vast population and escalating consumption of livestock, the country demonstrates heightened land demands. While China does not face a national-level food security threat, regional disparities are evident, with eight provincial districts facing potential food security risks. This study explored the challenges and pathways in maintaining food security and the visions to achieve it, emphasizing the importance of sustaining a balanced food consumption pattern, reducing food waste, improving environmentally friendly agriculture practices, formulating effective and continuous laws and regulations, and exploring potential land resource development to alleviate the pressure on arable land and ensure food security.

Self-triggered thermoelectric nanoheterojunction for cancer catalytic and immunotherapy.

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.

Mobile phone use among e-cyclists at red traffic lights: An observation study in a city of China.

OBJECTIVE: The observation study sought to explore the influencing factors associated with mobile phone use when e-cyclists were waiting for red lights at intersections, which provided a theoretical foundation for solving the potential traffic threat and developing management plans for e-cyclists. METHODS: Data regarding e-cyclists were collected through camera conducted at the entrance of multiple intersections in Zhenjiang, China in July 2020. The data was reviewed by playing frame by frame. A statistical analysis was performed with the statistical package SPSS software. After conducting univariate logistic analysis on study variables, the multivariate analysis was adopted based on the binary logit regression model. RESULTS: Among the 1166 e-cyclists observed, 15.01% (n = 175) e-cyclists had operated their mobile phones while waiting for red lights. Young e-cyclists, delivery cyclists were more likely to be involved with mobile phone use. Furthermore, mobile phone use was more observed at intersections in suburban areas and with long waiting time. E-cyclists, who was carrying a child, rarely used mobile phone. All intersections during off-peak times showed an increase in mobile phone use. The results also show that neither e-cyclists themselves nor traffic managers are aware of the risks of mobile phone use and the impact on traffic safety while waiting for a red light. CONCLUSIONS: The findings of this research revealed the factors influencing mobile phone use of e-cyclists while waiting for a red light, and indicated that education and behavioral intervention need to be strengthened to improve riding safety at intersections. These results will be helpful in developing programs of electric bicycle management.

Thermal stressed human immunodeficiency virus type 1 nucleocapsid protein NCp7 maintains nucleic acid-binding activity.

The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is a small, highly basic nucleic acid (NA)-binding protein with two CCHC zinc-finger motifs. In this study, we report for the first time, to our knowledge, that thermal stressed HIV-1 NCp7 maintained NA-binding activity. About 41.3% of NCp7 remained soluble after incubated at 100 °C for 60 min, and heat-treated NCp7 maintained its abilities to bind to HIV-1 packaging signal (Psi) and the stem-loop 3 of the Psi. At high or very high degrees of sequence occupancy, NCp7 inhibited first-strand cDNA synthesis catalyzed by purified HIV-1 reverse transcriptase, and heat-treated NCp7 maintained the inhibition. Moreover, both EDTA-treated and H23K + H44K double mutant of NCp7 inhibited first-strand cDNA synthesis, demonstrating that the NA-binding activity of NCp7 at high NC:NA ratios is independent on its zinc-fingers. These results may benefit further investigations of the structural stability and function of NCp7 in viral replication.

Preparation and uranium (VI) biosorption for tri-amidoxime modified marine fungus material.

The preparation, characterization, and uranium (VI) adsorption properties of tri-amidoxime modified marine fungus material (ZZF51-GPTS-EDA-AM/ZGEA) were investigated in this study. ZGEA was synthesized by four steps of condensation, nucleophilic substitution, electrophilic addition, and nitrile amidoxime and characterized by a series of methods containing FT-IR, TGA, SEM, and BET. Contrasted with uranium (VI) adsorption capacity of original fungus mycelium (15.46 mg g-1) that of the functional material (584.60 mg g-1) was great under the optimal factors such as uranium (VI) ion concentration 40 mg L-1, solid-liquid ratio 50 mg L-1, pH of solution 5.5, and reaction time 120 min. The above data were obtained by the orthogonal method. The cyclic tests showed that ZGEA had good regeneration performance, and it could be recycled at least five adsorption-desorption processes. The thermodynamic experimental adsorption result fitted Langmuir and Freundlich models, which explored monolayer and double layers of uranium (VI) adsorption mechanism, and the kinetic adsorption results were in better consistent with the pseudo-second-order and pseudo-first-order dynamic models (R2 > 0.999).

Preparation of hollow magnetic molecularly imprinted polymer and its application in silybin recognition and controlled release.

In this study, a new type of drug delivery carrier, the hollow magnetic silybin molecularly imprinted polymer (HMMIP) with a unique core-shell structure where the hollow magnetic core Fe3O4 was wrapped by mesoporous silica and imprinted layer, was prepared from methacrylic acid (MAA, functional monomer), ethylene glycol dimethacrylate (EGDMA, cross-linker), and silybin (a drug template) by reverse atom radical transfer polymerization method (RATRP), and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometer (XRD), vibrating sample magnetometer (VSM), thermo-gravimetric analysis (TGA), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller analysis (BET). Its adsorption performance was evaluated by the isotherm/kinetic models and the selectivity for silybin with 15.40 mg g-1 of adsorption capacity and 2.13 of selectivity factor α, respectively. The drug release experiment showed the prepared polymer had the properties of silybin sustained release agent, because it could last to release silybin for 36 h in the medium of pH 2.0 at physiological temperature. In addition, the resuability experiment indicated the imprinted material had the good stability and reproducibility. So HMMIP should be of the potential value applied in drug delivery in the future.

Integrated transcriptomic and metabolomic analyses of a wax deficient citrus mutant exhibiting jasmonic acid-mediated defense against fungal pathogens.

Naturally, resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration. We found a spontaneous mutant of 'Newhall' navel orange (Citrus sinensis Osbeck) (MT) with broad-spectrum protections against fungal pathogens in the orchard, postharvest-storage, and artificial inoculation conditions. To understand the defense mechanism of MT fruit, we constructed a genome-scale metabolic network that integrated metabolome and transcriptome datasets. The coordinated transcriptomic and metabolic data were enriched in two sub-networks, showing the decrease in very long chain fatty acid (by 41.53%) and cuticular wax synthesis (by 81.34%), and increase in the synthesis of jasmonic acid (JA) (by 95.23%) and JA-induced metabolites such as 5-dimethylnobietin (by 28.37%) in MT. Furthermore, cytological and biochemical analyses confirmed that the response to fungal infection in MT was independent of wax deficiency and was correlated with the levels of jasmonates, and the expression of plant defensin gene PDF1.2. Results of exogenous application of MeJA and JA inhibitors such as propyl gallate proved that JA-mediated defense contributes to the strong tolerance against pathogens in MT. Our results indicated that jasmonate biosynthesis and signaling are stimulated by the fatty acid redirection of MT, and participate in the tolerance of pathogenic fungi.

Distinct Carotenoid and Flavonoid Accumulation in a Spontaneous Mutant of Ponkan (Citrus reticulata Blanco) Results in Yellowish Fruit and Enhanced Postharvest Resistance.

As the most important fresh fruit worldwide, citrus is often subjected to huge postharvest losses caused by abiotic and biotic stresses. As a promising strategy to reduce postharvest losses, enhancing natural defense by potential metabolism reprogramming in citrus mutants has rarely been reported. The yellowish spontaneous mutant of Ponkan (Citrus reticulata Blanco) (YP) was used to investigate the influence of metabolism reprogramming on postharvest performance. Our results show that reduced xanthophyll accumulation is the cause of yellowish coloring of YP and might be attributed to the reduced carotenoid sequestration capacity and upregulated expression of carotenoid cleavage dioxygenase genes. Constantly higher levels of polymethoxylated flavones (PMFs) during the infection and the storage stage might make significant contribution to the more strongly induced resistance against Penicillium digitatum and lower rotting rate. The present study demonstrates the feasibility of applying bud mutants to improve the postharvest performance of citrus fruits.

Network analysis of postharvest senescence process in citrus fruits revealed by transcriptomic and metabolomic profiling.

Citrus (Citrus spp.), a nonclimacteric fruit, is one of the most important fruit crops in global fruit industry. However, the biological behavior of citrus fruit ripening and postharvest senescence remains unclear. To better understand the senescence process of citrus fruit, we analyzed data sets from commercial microarrays, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry and validated physiological quality detection of four main varieties in the genus Citrus. Network-based approaches of data mining and modeling were used to investigate complex molecular processes in citrus. The Citrus Metabolic Pathway Network and correlation networks were constructed to explore the modules and relationships of the functional genes/metabolites. We found that the different flesh-rind transport of nutrients and water due to the anatomic structural differences among citrus varieties might be an important factor that influences fruit senescence behavior. We then modeled and verified the citrus senescence process. As fruit rind is exposed directly to the environment, which results in energy expenditure in response to biotic and abiotic stresses, nutrients are exported from flesh to rind to maintain the activity of the whole fruit. The depletion of internal substances causes abiotic stresses, which further induces phytohormone reactions, transcription factor regulation, and a series of physiological and biochemical reactions.

Human mesenchymal stem cells possess different biological characteristics but do not change their therapeutic potential when cultured in serum free medium.

INTRODUCTION: Mesenchymal stem cells (MSCs) are widely investigated in clinical researches to treat various diseases. Classic culture medium for MSCs, even for clinical use, contains fetal bovine serum. The serum-containing medium (SCM) seems a major obstacle for MSCs-related therapies due to the risk of contamination of infectious pathogens. Some studies showed that MSCs could be expanded in serum free medium (SFM); however, whether SFM would change the biological characteristics and safety issues of MSCs has not been well answered. METHODS: Human umbilical cord mesenchymal stem cells (hUC-MSCs) were cultured in a chemical defined serum free medium. Growth, multipotency, surface antigen expression, telomerase, immunosuppressive ability, gene expression profile and genomic stability of hUC-MSCs cultured in SFM and SCM were analyzed and compared side by side. RESULTS: hUC-MSCs propagated more slowly and senesce ultimately in SFM. SFM-expanded hUC-MSCs were different from SCM-expanded hUC-MSCs in growth rate, telomerase, gene expression profile. However, SFM-expanded hUC-MSCs maintained multipotency and the profile of surface antigen which were used to define human MSCs. Both SFM- and SCM-expanded hUC-MSCs gained copy number variation (CNV) in long-term in vitro culture. CONCLUSION: hUC-MCSs could be expanded in SFM safely to obtain enough cells for clinical application, meeting the basic criteria for human mesenchymal stem cells. hUC-MSCs cultured in SFM were distinct from hUC-MSCs cultured in SCM, yet they remained therapeutic potentials for future regenerative medicine.

Efficiency of transcellular transport and efflux of flavonoids with different glycosidic units from flavonoids of Litsea coreana L. in a MDCK epithelial cell monolayer model.

Although there is strong evidence to suggest that beneficial effects of the flavonoids in human health, the extent to which flavonoids are absorbed and the mechanisms involved are controversial. The objective of this study was to determine the bi-directional permeability and efflux characters of the four main flavonoids with different glycosidic units isolated from flavonoids of Litsea coreana L. and to discuss the transport mechanisms using the epithelial cell model MDCK. The transport of the four main flavonoid glycosides at concentration of 40, 80, 160 µM was concentration-dependent in both apical to basolateral and the reverse direction. Contemporary, the influx and efflux of the flavonoid glycosides were temperature-dependent and pH-dependent at concentration of 80 µM, and transport of flavonoid glycosides was obviously decreased when experiments performed in the presence of 1mM sodium azide (an ATP inhibitor). Uptake of quercetin-3-O-ß-D-glucoside or kaempferol-3-O-ß-D-glucoside was inhibited by 50 µM phloridzin, a specific and competitive inhibitor of SGLT. Moreover, the flavonoids exhibited significantly larger basolateral to apical Papp than that of the reverse direction, suggesting the existence of efflux mechanisms. The 50 µM verapamil, a chemical inhibitor of P-glycoprotein (P-gp), had no effect on the transport of four flavonoid glycosides. However, 50 µM MK-571 or 1 mM probenecid, MRP2 inhibitors, led to an apparently decrease in the efflux of flavonoid glycosides. Therefore, MRP2 but P-gp may be involved in the transport of the four flavonoid glycosides. Taken together, the experimental observations in our study provide useful information for pharmacological applications of flavonoids with different glycosidic units from flavonoids of L. coreana L.

Tembusu virus in ducks, china.

In China in 2010, a disease outbreak in egg-laying ducks was associated with a flavivirus. The virus was isolated and partially sequenced. The isolate exhibited 87%-91% identity with strains of Tembusu virus, a mosquito-borne flavivirus of the Ntaya virus group. These findings demonstrate emergence of Tembusu virus in ducks.

[Molecular genetic evolution analysis of new A(H1N1) influenza virus].

In order to analyze the molecular epidemiology of A (H1N1) influenza virus in 2009, the complete genome sequences of influenza strains from different host sources downloaded from the NCBI were analyzed on genetic evolution by DNAstar software in this research. The results showed that 79 mutation sites of new A (H1N1) influenza virus were observed compared to previous human A (H1N1) influenza strain, including 14 mutation sites new in all A (H1N1) influenza sources and 37 mutation sites only observed in swine strain. A significant difference was represented in antigenic sites between new A (H1N1) influenza strain and the previous human A (H1N1) strain. This phenomenon shows the new A (H1N1) influenza strain is either originated from the recombination of human and swine strain or from the infection in pig populations and gradual mutation to human tansmission, which remains to be further studied.