Biomimetic Nano-Immunoactivator via Ionic Metabolic Modulation for Strengthened NIR-II Photothermal Immunotherapy.

Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.

Effects of combined process of reactive ion etching and dynamic chemical etching on UV laser damage resistance and surface quality of fused silica optics.

We investigate the interest of combined process of reactive ion etching (RIE) and dynamic chemical etching (DCE) as a final step after polishing to improve the laser damage resistance of fused silica optics at the wavelength of 355 nm. The investigation is carried out on the polished fused silica optics by changing the RIE depth while keeping the DCE depth fixed. We evidence that the combined etching process can effectively remove the damage precursors on the fused silica surface and thus improve its laser-induced damage threshold exceeding the level of the deep HF-etched surface. The effects of the combined etching depth on the surface roughness and surface error are also studied systematically. We show that the combined shallow etching can achieve better overall surface quality. Deeper etching will cause surface quality degradation of the fused silica optics, which is believed to be associated with the chemical etching during the combined process. Given that HF acid processing will degrade the surface quality of fused silica optics, the combined shallow etching appears as a pertinent alternative to HF-based deep etching.

Effect of PVA coating on the electric field intensity distribution and laser damage performance of fused silica optics surfaces.

A facile method was proposed to enhance the laser damage performance of the fused silica optics by coating a PVA film on the rear surface of the optics. FDTD simulation result suggests that the PVA coating with suitable thickness can transfer the maximal electric field intensity from the rear surface to the interface between the coating and air, and reduce the electric field intensity of the rear surface remarkably. LIDT tests reveal that the LIDT of fused silica with PVA coating changed periodically with respect to the coating thickness, which agrees well with the tendency predicted by FDTD simulation. Finally, PVA coatings with a thickness of 60 nm and 300 nm can both improve the LIDT of AMP-treated fused silica by ~20%, which provide a potential to be applied in high power laser facility.

Growth mechanism of one-step self-masking reactive-ion-etching (RIE) broadband antireflective and superhydrophilic structures induced by metal nanodots on fused silica.

This work presents a low-cost, simple, convenient, advanced technology to prepare large-area defect-free subwavelength structures (SWSs). SWSs were obtained by a metal-induced one-step self-masking RIE process on a fused-silica surface, in which metal-fluoride (mainly ferrous-fluoride) nanodots were used to induce and gather stable fluorocarbon polymer etching inhibitors in the RIE polymers as masks. The SWS growth processes are visible with an increase in etching time and some exhibit prominent broadband antireflective properties from the visible to the near-infrared wavelength range. Transmission in the 600-900-nm range increased from approximately 93% for the polished fused silica to above 99% for the double-side SWSs on fused silica. A theoretical simulation by a finite-difference time-domain method agreed well with the experiments. Moreover, the surface of the SWSs exhibits excellent superhydrophilic properties.

Reaction ion etching process for improving laser damage resistance of fused silica optical surface.

Laser induced damage of fused silica optics occurs primarily on optical surface or subsurface resulting from various defects produced during polishing/grinding process. Many new kinds of surface treatment processes are explored to remove or control the defects on fused silica surface. In this study, we report a new application of reaction ion etching (RIE)-based surface treatment process for manufacture of high quality fused silica optics. The influence of RIE processes on laser damage resistance as a function of etching depth and the evolution of typical defects which are associated with laser damage performance were investigated. The results show that the impurity element defects and subsurface damage on the samples surface were efficiently removed and prevented. Pure silica surface with relatively single-stable stoichiometry and low carbon atomic concentration was created during the etching. The laser damage resistance of the etched samples increased dramatically. The increase of roughness and ODC point defect with deeper etching are believed to be the main factors to limit further increase of the damage resistance of fused silica. The study is expected to contribute to the development of fused silica optics with high resistance to laser induced degradation in the future.

Biomimetic "Gemini nanoimmunoregulators" orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages.

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

Ag-modified CuO cavity arrays as a SERS-electrochemical dual signal platform for thiram detection.

Rapid and sensitive determination of pesticide residues in fruits and vegetables is critical for human health and ecosystems. This paper used an Ag-modified CuO sphere-cavity array (CuO@Ag) electrode as a thiram SERS/electrochemical dual readout detection platform. Numerous Raman "hotspots" generated by uniformly distributed silver nanoparticles, charge transfer at the CuO@Ag interface, and the formation of Ag-thiram complexes contribute to the significant enhancement of this SERS substrate, which results in excellent SERS performance with an enhancement factor up to 1.42 × 106. When using SERS as the readout technique, the linear range of the substrate for thiram detection was 0.05-20 nM with a detection limit (LOD) of up to 0.0067 nM. Meanwhile, a correlation between the value of change in current density and thiram concentration was established due to the formation of stable complexes of thiram with Cu2+ generated at specific potentials. The linear range of electrochemical detection was 0.05-20.0 µM, and the detection limit was 0.0167 µM. The newly devised dual-readout sensor offers notable sensitivity and stability. The two signal readout methods complement each other in terms of linear range and detection limit, making it a convenient tool for assessing thiram residue levels in agro-food. At the same time, the combination of commercially available portable equipment makes on-site monitoring possible.

Rapid discrimination of urine specific gravity using spectroscopy and a modified combination method based on SPA and spectral index.

To achieve high-accuracy urine specific gravity discrimination and guide the design of four-waveband multispectral sensors. A modified combination strategy was attempted to be proposed based on the successive projections algorithm (SPA) and the spectral index (SI) in the present study. First, the SPA was used to select four spectral variables in the full spectra. Second, the four spectral variables were mathematically transformed by SI to obtain SI values. Then, SPA gradually fusions the SI values and establishes models to identify USG. The results showed that the SPA can screen out the four characteristic wavelengths related to the measured sample attributes. SIs can be used to improve the performance of constructed prediction models. The best model only involves four spectral variables and 1 SI value, with high accuracy (91.62%), sensitivity (0.9051), and specificity (0.9667). The results reveal that m-SPA-SI can effectively distinguish USG and provide design guidance for 4-wavelength multispectral sensors.

Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1.

Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme branching from glycolysis in the three-step serine biosynthetic pathway. Recent evidence has shown that PHGDH is amplified in human breast cancer and melanoma and plays a key role in cancer metabolism. However, PHGDH expression in glioma and a potential non-metabolic role in tumorigenesis have not been reported. We analyzed PHGDH levels in specimens from glioma patients and found that PHGDH, although negative in normal brain tissues, was highly expressed in astrocytic tumors and increasingly expressed in more aggressive cancer types. Inhibition of PHGDH expression in glioma cells downregulated the expression of VEGF, MMP-2, CHK2 and cyclin D1 and reduced glioma cell proliferation, invasion and tumorigenicity in vitro and in vivo. Interestingly, we found that the oncogenic transcription factor FOXM1 was also downregulated in PHDGH-silenced glioma cells. Using LC/LC MS analysis, we identified PHGDH as a novel binding partner of FOXM1. PHGDH interacted with and stabilized FOXM1 at the protein level, promoting the proliferation, invasion and tumorigenicity of glioma cells. Our data identified PHGDH as a potential prognostic marker of glial brain tumors and identified a non-metabolic role for PHGDH in glioma tumorigenesis, providing a novel angle of targeting the PHGDH-FOXM1 axis in future brain tumor therapy.

Iodine Deficiency of Breastfeeding Mothers and Infants from 2012 to 2019 in Zhengzhou, China.

To investigate iodine status and characteristics of breastfeeding women and infants in Zhengzhou after the implementation of the new national standard of iodine in edible salt, so as to provide the basis for formulating prevention and control measures. Urine samples from 28,730 infants aged 0-2 years and 17,977 breastfeeding women who received preventive health care in 12 districts/cities of Zhengzhou from 2012 to 2019 were collected to measure urinary iodine concentration (UIC). A total of 350 pairs of unweaned infants and their mothers were included in this study. After the implementation of the new national standard of iodine in edible salt, the iodine deficiency of infants aged 0-2 years showed a trend of decreasing first and then increasing, but generally the iodine nutrition of infants aged 0-2 years was at the appropriate level in 8 years. There was a gradual decrease in iodine deficiency among breastfeeding women over an 8-year period. And the median UIC of breastfeeding women in 8 years was at iodine nutrition appropriate level. In addition, the UIC of breastfeeding mothers was positively associated with that of infants (r = 0.104, P = 0.004). After the implementation of the new national standard of iodine in edible salt, breastfeeding women and infants in Zhengzhou generally were at an appropriate level of iodine nutrition, and there was a significant positive correlation between the UIC of breastfeeding mothers and infants.

Combination of metabolome and proteome analyses provides insights into the mechanism underlying growth differences in Acipenser dabryanus.

To analyze the differences between different-sized Acipenser dabryanus, we randomly selected 600 3-month-old A. dabryanus juveniles. Four months later, the blood and white muscle of these fish were analyzed. The results showed no significant difference in the length-weight relationship (LWR) b value between the large and small A. dabryanus. The levels of serum growth hormone (gh) and insulin-like growth factor 1 (igf1) in the large A. dabryanus were significantly lower than those in the small, whereas the activity levels of Total superoxide dismutase (T-sod) and catalase (cat) were opposite to the results of gh and igf1. A total of 212 and 245 metabolites showed significant changes in the positive and negative polarity mode, respectively. Among 3,308 proteins identified, 69 proteins showed upregulated expression, and 185 proteins showed downregulated expression. These results indicated that the growth advantage of A. dabryanus was closely related to glycolysis, protein synthesis, and antioxidant function.

A High-Throughput Method Based on Microculture Technology for Screening of High-Yield Strains of Tylosin-Producing Streptomyces fradiae.

Tylosin is a potent veterinary macrolide antibiotic produced by the fermentation of Streptomyces fradiae; however, it is necessary to modify S. fradiae strains to improve tylosin production. In this study, we established a high-throughput, 24-well plate screening method for identifying S. fradiae strains that produce increased yields of tylosin. Additionally, we constructed mutant libraries of S. fradiae via ultraviolet (UV) irradiation and/or sodium nitrite mutagenesis. A primary screening of the libraries in 24-well plates and UV spectrophotometry identified S. fradiae mutants producing increased yields of tylosin. Mutants with tylosin yield 10% higher than the wild-type strain were inoculated into shake flasks, and the tylosin concentrations produced were determined by high-performance liquid chromatography (HPLC). Joint (UV irradiation and sodium nitrite) mutagenesis resulted in higher yields of mutants with enhanced tylosin production. Finally, 10 mutants showing higher tylosin yield were re-screened in shake flasks. The yield of tylosin A by strains UN-C183 (6767.64 ± 82.43 µg/ml) and UN-C137 (6889.72 ± 70.25 µg/ml) was significantly higher than that of the wild-type strain (6617.99 ± 22.67 µg/ml). These mutant strains will form the basis for further strain breeding in tylosin production.

One-step hydrothermal synthesis of nitrogen-doped carbon dots for high-sensitivity visual detection of nitrite and ascorbic acid.

Ascorbic acid (AA) is an indispensable vitamin for the human body and is associated with critical processes of human metabolism. However, excessive intake of AA can also have a negative impact on human health. Nitrite is a commonly used food additive, and its overdose can increase the risk of cancer. Therefore, the detection of nitrite and vitamins is generally recognized to be meaningful. In this study, red-fluorescence and yellow-fluorescence CDs (r-CDs/y-CDs) were synthesized by a one-step hydrothermal method using o-phenylenediamine as the only carbon source. These two types of CDs exhibited good detection accuracy, detection limit and selectivity towards nitrite and AA (the detection limits are 0.47 µM and 45.1 µM, respectively). The long wavelength luminescent CDs prepared in this experiment also have high quantum yield (QY), which is of great significance to the visual detection effect. Under weak acidic conditions, the amino group on the surface of r-CDs can coordinate with nitrite and react to generate diazo groups, leading to the fluorescence quenching of CDs. The coordination between the y-CDs and the amino group on the surface of AA connects the adjacent y-CDs to form aggregates, which increases the non-radiative transition of electrons and induces the fluorescence quenching of CDs. This study proposes a new idea for the preparation of carbon dots for the determination of NO2- and AA in solutions, which expands the application of fluorescent CD detection.

Fully Inkjet Printing Preparation of a Carbon Dots Multichannel Microfluidic Paper-Based Sensor and Its Application in Food Additive Detection.

Microfluidic paper-based sensors as a new type of microsample detection technology are widely used in medical diagnosis, environmental monitoring, and food safety testing. Inkjet printing has the advantages of simplicity, speed, flexibility, high resolution, low cost, and efficient mass production and has become one of the most cutting-edge technologies in the manufacture of paper-based sensors. In this work, a fully inkjet printing preparation method was proposed for paper-based sensors, which can achieve high-precision, multichannel, and visual fluorescence detection. Three kinds of fluorescent carbon dots (CDs; r-CDs, b-CDs, and y-CDs) were fabricated into inkjet ink by adding a suitable ratio of solvent, PEG, and surfactant FS3100 to control its viscosity, surface tension, and other influencing factors, obtaining the best-visualized fluorescence response on paper. To optimize the full inkjet printing process of the paper-based sensor, we studied the influence of factors such as the hydrophobic material AKD formula, postprocessing conditions, and the structure of the hydrophilic and hydrophobic channels on the paper-based detection accuracy, and it was found that proper AKD concentration, curing time, and temperature can make AKD fully react with paper-based surface groups and produce more hydrophobic groups on the surface and inside of the filter paper, which can form paper-based microfluidic sensors with clear boundaries and fast transmission speed at low cost and high efficiency. The fabricated sensor is used for the fluorometric determination of vitamin C (AA), NO2-, and sunset yellow (SY) at the same time, and the limits of visual detection by eyes are 6 mmol/L (NO2-), 60 µmol/L (SY), and 40 mmol/L (AA). The mechanism of inkjet printing is investigated in detail, which is simple, reliable, and easy to realize mass production and can realize highly sensitive, on-site, and visual detection for food additives.

An ink-jet printed dual-CD ratiometric fluorescent paper-based sensor for the visual detection of Cu2.

Copper ion (Cu2+) plays an important role in the human body because it is beneficial for metabolism. However, an excessive or slight amount of Cu2+ can cause various symptoms. Therefore, it is necessary for human health to realize the trace and visual detection of Cu2+. Referring to traditional fluorescence test papers, the qualitative and semi-quantitative detection of Cu2+ could be realized by a dual-carbon dots (CDs) ratiometric fluorescent paper-based sensor with the advantages of environmental protection, portability and low cost. In this paper, the inkjet-printed test paper with the best mixing ratio of the two CDs has been researched to maximize the spectral energy transfer of ion detection (maximum color gamut expansion). Among them, the preparation method of b-CDs has been improved, increasing the photoluminescence quantum yield (PLQY) to 88.9%. The sensitivity detection limit of the double emission ratio sensor was 0.15 nM in solution, and the human eye can distinguish at least 3 µmol L-1 Cu2+ in the paper-based sensor. Compared with the traditional single-emission sensor, the human eye was more sensitive to the color change of the emission ratio sensor. The results indicate that we not only realized the micro detection of Cu2+ with convenient methods, but also provided a promising strategy for the visual detection of Cu2+.

Haplotype-resolved genome of diploid ginger (Zingiber officinale) and its unique gingerol biosynthetic pathway.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger 'Zhugen', a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3'H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

Quadratic Meta-Reflectors Made of HfO2 Nanopillars with a Large Field of View at Infrared Wavelengths.

Metasurfaces, being composed of subwavelength nanostructures, can achieve peculiar optical manipulations of phase, amplitude, etc. A large field of view (FOV) is always one of the most desirable characteristics of optical systems. In this study, metasurface-based quadratic reflectors (i.e., meta-reflectors) made of HfO2 nanopillars are investigated to realize a large FOV at infrared wavelengths. First, the geometrical dependence of HfO2 nanopillars' phase difference is analyzed to show the general principles of designing infrared HfO2 metasurfaces. Then, two meta-reflectors with a quadratic phase profile are investigated to show their large FOV, subwavelength resolution, and long focal depth. Furthermore, the two quadratic reflectors also show a large FOV when deflecting a laser beam with a deflecting-angle range of approximately ±80°. This study presents a flat optical metamaterial with a large FOV for imaging and deflecting, which can greatly simplify the optical-mechanical complexity of infrared systems, particularly with potential applications in high-power optical systems.

High-Efficiency Metasurfaces with 2π Phase Control Based on Aperiodic Dielectric Nanoarrays.

In this study, the high-efficiency phase control Si metasurfaces are investigated based on aperiodic nanoarrays unlike widely-used period structures, the aperiodicity of which providing additional freedom to improve metasurfaces' performance. Firstly, the phase control mechanism of Huygens nanoblocks is demonstrated, particularly the internal electromagnetic resonances and the manipulation of effective electrical/magnetic polarizabilities. Then, a group of high-transmission Si nanoblocks with 2π phase control is sought by sweeping the geometrical parameters. Finally, several metasurfaces, such as grating and parabolic lens, are numerically realized by the nanostructures with high efficiency. The conversion efficiency of the grating reaches 80%, and the focusing conversion efficiency of the metalens is 99.3%. The results show that the high-efficiency phase control metasurfaces can be realized based on aperiodic nanoarrays, i.e., additional design freedom.

N-Acetyl Serotonin Protects Neural Progenitor Cells Against Oxidative Stress-Induced Apoptosis and Improves Neurogenesis in Adult Mouse Hippocampus Following Traumatic Brain Injury.

In this study, with primary mouse neural progenitor cells (NPCs), we investigated the neuroprotective effect of a tropomyosin-related kinase receptor B (TrkB) agonist, N-acetyl serotonin (NAS), against hydrogen peroxide (H2O2)-induced toxicity. We found that pre-incubation with NAS not only ameliorates H2O2-induced cell viability loss, lactate dehydrogenase (LDH) release, and proliferative and migratory capacity impairments, but counteracts H2O2-triggered production of nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) in a dose-dependent manner. Additionally, pre-treatment with NAS was able to attenuate H2O2-induced apoptosis in NPCs, evidenced by the decreased percentage of apoptotic cells and altered expression of apoptosis-related factors. Furthermore, in differentiated NPCs, NAS improves H2O2-induced reduction in neurite growth. Mechanistic studies revealed that the protective effects of NAS in NPCs may be mediated by the TrkB/PI3K/Akt/ cAMP response element binding protein (CREB) signaling cascades. In a mouse traumatic brain injury (TBI) model, we found that systemic administration of 30 mg/kg NAS could improve hippocampal neurogenesis, manifested by the increased number of SOX-2-positive cells and increased expression of phosphorylated CREB in the dentate gyrus (DG) area. Treatment with NAS also ameliorates cognitive impairments caused by TBI, as assessed by Y-maze and contextual and cued fear conditioning tests. Taken together, these results provide valuable insights into the neuroprotective and neuroregenerative effects of NAS, suggesting it may have therapeutic potential for the treatment of TBI.

Non-destructive evaluation of UV pulse laser-induced damage performance of fused silica optics.

The surface laser damage performance of fused silica optics is related to the distribution of surface defects. In this study, we used chemical etching assisted by ultrasound and magnetorheological finishing to modify defect distribution in a fused silica surface, resulting in fused silica samples with different laser damage performance. Non-destructive test methods such as UV laser-induced fluorescence imaging and photo-thermal deflection were used to characterize the surface defects that contribute to the absorption of UV laser radiation. Our results indicate that the two methods can quantitatively distinguish differences in the distribution of absorptive defects in fused silica samples subjected to different post-processing steps. The percentage of fluorescence defects and the weak absorption coefficient were strongly related to the damage threshold and damage density of fused silica optics, as confirmed by the correlation curves built from statistical analysis of experimental data. The results show that non-destructive evaluation methods such as laser-induced fluorescence and photo-thermal absorption can be effectively applied to estimate the damage performance of fused silica optics at 351 nm pulse laser radiation. This indirect evaluation method is effective for laser damage performance assessment of fused silica optics prior to utilization.