Clinical significance of PLT for diagnosis and treatment monitoring in imported malaria.

To evaluate the clinical significance of PLT, MPV, and PDW in monitoring malaria treatment efficacy and predicting disease progression. A total of 31 patients with imported malaria were selected as the observation group, while 31 non-malaria patients with fever were selected as controls. The observation group was subdivided into a complication group and a non-complication group according to the occurrence of complications during treatment. Additionally, on the 1st day (within 24 h), the 3rd day, and the 5th day following admission, a comprehensive blood routine examination, Plasmodium microscopic examination, and colloidal gold assay were conducted. The blood routine examination results were compared before and after treatment among patients in the observation group and the control group. Moreover, the study involved dynamic monitoring and analysis of the levels and variations in PLT, MPV, and PDW within both the complication group and the non-complication group. The Plasmodium density was negatively correlated with PLT before treatment. There were significant differences were observed in PLT, MPV, and PDW (P < 0.05) within the observation group before and after treatment. Notably, there were no significant alterations in red blood cell (RBC), hemoglobin (Hb), and white blood cell (WBC) counts (P > 0.05) within the observation group before and after treatment. The PLT, MPV, and PDW levels in the complication group and the non-complication group exhibited an upward trend after treatment. Further, the PLT of patients in the complication group was significantly lower than that in the non-complication group. Additionally, the PLT, MPV, and PDW levels in the complication group and the non-complication group increased gradually from the time of admission to the 3rd and 5th day of treatment. Notably, the PLT in the complication group was consistently lower than that in the non-complication group. The continuous monitoring of PLT, MPV, and PDW changes plays a crucial role in assessing malaria treatment efficacy and prognosis in these individuals.

Investigation of artificial cells containing the Par system for bacterial plasmid segregation and inheritance mimicry.

A crucial step in life processes is the transfer of accurate and correct genetic material to offspring. During the construction of autonomous artificial cells, a very important step is the inheritance of genetic information in divided artificial cells. The ParMRC system, as one of the most representative systems for DNA segregation in bacteria, can be purified and reconstituted into GUVs to form artificial cells. In this study, we demonstrate that the eGFP gene is segregated into two poles by a ParM filament with ParR as the intermediate linker to bind ParM and parC-eGFP DNA in artificial cells. After the ParM filament splits, the cells are externally induced to divide into two daughter cells that contain parC-eGFP DNA by osmotic pressure and laser irradiation. Using a PURE system, we translate eGFP DNA into enhanced green fluorescent proteins in daughter cells, and bacterial plasmid segregation and inheritance are successfully mimicked in artificial cells. Our results could lead to the construction of more sophisticated artificial cells that can reproduce with genetic information.

SC912 inhibits AR-V7 activity in castration-resistant prostate cancer by targeting the androgen receptor N-terminal domain.

Androgen deprivation therapies (ADT) are the mainstay treatments for castration-resistant prostate cancer (CRPC). ADT suppresses the androgen receptor (AR) signaling by blocking androgen biosynthesis or inhibiting AR with antiandrogens that target AR's ligand-binding domain (LBD). However, the ADT's effect is short-lived, as the AR signaling inevitably arises again, which is frequently coupled with AR-V7 overexpression. AR-V7 is a truncated form of AR that lacks the LBD, thus being constitutively active in the absence of androgens and irresponsive to AR-LBD-targeting inhibitors. Though compelling evidence has tied AR-V7 to drug resistance in CRPC, pharmacological inhibition of AR-V7 is still an unmet need. Here, we discovered a small molecule, SC912, which binds to full-length AR as well as AR-V7 through AR N-terminal domain (AR-NTD). This pan-AR targeting relies on the amino acids 507-531 in the AR-NTD. SC912 also disrupted AR-V7 transcriptional activity, impaired AR-V7 nuclear localization and DNA binding. In the AR-V7 positive CRPC cells, SC912 suppressed proliferation, induced cell-cycle arrest, and apoptosis. In the AR-V7 expressing CRPC xenografts, SC912 attenuated tumor growth and antagonized intratumoral AR signaling. Together, these results suggested the therapeutic potential of SC912 for CRPC.

Phospholipid Epitaxial Assembly Behavior on a Hydrophobic Highly Ordered Pyrolytic Graphite Surface.

Supported lipid bilayers (SLBs) are excellent models of cell membranes. However, most SLBs exist in the form of phospholipid molecules standing on a substrate, making it difficult to have a side view of the phospholipid membranes. In this study, the phospholipid striped lamella with the arrangement of their alkane tails lying on highly ordered pyrolytic graphite (HOPG) was constructed by a spin coating method. Atomic force microscopy and molecular dynamics simulations are utilized to study the self-assembly of phospholipids on HOPG. Results show that various phospholipids with different packing parameters and electrical property are able to epitaxially adsorb on HOPG. 0.1 mg/mL Plasm PC (0.1 mg/mL) could form a striped monolayer with a width of 5.93 ± 0.21 nm and form relatively stable four striped layers with the concentration increasing to 1 mg/mL. The width of the DOPS multilayer is more than that of electroneutral lipids due to the static electrical repulsion force. This universal strategy sheds light on direct observation of the membrane structure from the side view and modification of 2D materials with amphiphilic biomolecules.

Regulation of species metabolism in synthetic community systems by environmental pH oscillations.

Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B (Saccharomyces cerevisiae), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO2. In addition, a three-species community is constructed with species A' (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD+ and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A'; G6P then enters species C to promote the metabolic reaction that converts NAD+ to NADH. The location of species A' and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA'B, CBA', and A'CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.

High aspect ratio plasmonic Au/Ag nanorods-mediated NIR-II photothermally enhanced nanozyme catalytic cancer therapy.

Chemodynamic therapy (CDT) is based on the endogenous generation of cytotoxic hydroxyl free radicals (·OH) with high specificity and selectivity between cancer and normal cells. However, its efficacy is often limited by the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME). Therefore, the combination of CDT with other strategy to realize synergistic therapy is necessary. Herein, a versatile plasmonic Au/Ag nanorods (abbreviated as Au/Ag NRs) via anisotropic Ag overgrowth on Au nanobipyramids was rationally devised to achieve synergistic nanozyme catalytic therapy and near infrared II (NIR-II) light induced photothermal therapy (PTT) with the guidance of computed tomography (CT) imaging. As TME contains high concentrations of H+ and H2O2, Au/Ag NRs exhibited peroxidase (POD) activity to catalyze H2O2 to produce ·OH, inducing cancer cell death. Meanwhile, Au/Ag NRs showed a preeminent NIR-II photothermal effect. More importantly, the enhanced ·OH generation by in-situ heating up resulting from PTT could conversely inhibit the expression of heat shock proteins (HSPs) to abate their resistance to PTT, realizing self-augmented synergistic effect. The NIR-II photothermally enhanced nanozyme catalytic cancer therapy validly inhibited the cancer proliferation, as demonstrated via both cell and animal assays. Moreover, ideal high-contrast CT imaging was realized, owing to the X-ray attenuation capability of elemental Au. The multifunctional Au/Ag NRs hold potential in oncotherapy with imaging capability, high efficiency and low side effects.

C:N:P stoichiometric variations of herbs and its relationships with soil properties and species relative abundance along the Xiaokai River irrigation in the Yellow River Delta, China.

Introduction: Soil salinity is known to affect plant performance and nutrient stoichiometry by altering their ecophysiology, and thus playing a crucial role in determining plant distribution patterns and nutrient cycles in salinized ecosystems. However, there was little consensus on the effects of salinity stress on plant C, N, and P stoichiometries. Moreover, determining the relationships between species relative species abundance and plant C, N, and P stoichiometries can help to understand the different adaptive strategies between the common and rare species as well as the community assembly process. Methods: We determined the plant C, N, P stoichiometries at the community and species levels and the relative abundance of species as well as the corresponding soil properties from five sampling sites along a soil salinity gradient in the Yellow River Delta, China. Results and Discussion: We found that the C concentration of belowground part increased with soil salinity. Meanwhile, plant community N concentration and C:N ratio tended to decrease with soil salinity, whereas the P concentration, C:P, and N:P ratios exhibited the opposite trends. This indicated that N use efficiency increased, while P use efficiency decreased with soil salinity. Moreover, the decreased N:P ratio indicated that N limitation was gradually aggravated along the soil salinity gradient. The soil C:P ratio and P concentration were the major factors of plant C, N, and P stoichiometries in the early growth stage, whereas the soil pH and P concentration were the major factors of plant C, N, and P stoichiometries in the late growth stage. Compared with that of the rare species, the C:N:P stoichiometry of the most common species was medium. Moreover, the intraspecific variations in the aboveground part N:P ratio and belowground part C concentration showed a significant correlation with species' relative abundance, which indicated that higher intraspecific trait variation might facilitate greater fitness and survival opportunities in environments with high heterogeneity. Conclusion: Our results revealed that the plant community C:N:P stoichiometry and its determining soil properties varied with plant tissues as well as sampling seasons, and emphasized the importance of intraspecific variation in determining the functional response of plant communities to salinity stress.

A double-suture cerclage reduction technique with Nice knots for comminuted patella fractures (AO/OTA 34-C3).

BACKGROUND: Comminuted patella fractures place high demands on surgeons' surgical skills. We used a double-suture cerclage reduction with Nice knots as an intra-operative reduction technique to displaced comminuted patella fractures. METHODS: Patients were divided into two groups by whether or not an intra-operative suture cerclage reduction technique was used. Fragments count, surgical time, quality of the reduction, and fracture healing time were recorded. The postoperative function was assessed by Böstman score and range of motion. RESULTS: With the inclusion and exclusion criteria, 48 patients we included in the cohort between Sept. 2016 and Oct. 2021. The double-suture cerclage reduction technique with a Nice knot achieved a satisfactory reduction. When the number of fragments was over 5, this technique showed significant advantages in saving surgery time. CONCLUSIONS: In this study, the double-suture cerclage reduction technique combined with the Nice knot shows significant advantages for displaced highly comminuted patella fractures. This technique simplifies the operation and saves surgical time, which is helpful for clinical practice.

Light-Harvesting Artificial Cells Containing Cyanobacteria for CO2 Fixation and Further Metabolism Mimicking.

The bottom-up constructed artificial cells help to understand the cell working mechanism and provide the evolution clues for organisms. The energy supply and metabolism mimicry are the key issues in the field of artificial cells. Herein, an artificial cell containing cyanobacteria capable of light harvesting and carbon dioxide fixation is demonstrated to produce glucose molecules by converting light energy into chemical energy. Two downstream "metabolic" pathways starting from glucose molecules are investigated. One involves enzyme cascade reaction to produce H2 O2 (assisted by glucose oxidase) first, followed by converting Amplex red to resorufin (assisted by horseradish peroxidase). The other pathway is more biologically relevant. Glucose molecules are dehydrogenated to transfer hydrogens to nicotinamide adenine dinucleotide (NAD+ ) for the production of nicotinamide adenine dinucleotide hydride (NADH) molecules in the presence of glucose dehydrogenase. Further, NADH molecules are oxidized into NAD+ by pyruvate catalyzed by lactate dehydrogenase, meanwhile, lactate is obtained. Therefore, the cascade cycling of NADH/NAD+ is built. The artificial cells built here pave the way for investigating more complicated energy-supplied metabolism inside artificial cells.

Artificial organelles for sustainable chemical energy conversion and production in artificial cells: Artificial mitochondrion and chloroplasts.

Sustainable energy conversion modules are the main challenges for building complex reaction cascades in artificial cells. Recent advances in biotechnology have enabled this sustainable energy supply, especially the adenosine triphosphate (ATP), by mimicking the organelles, which are the core structures for energy conversion in living cells. Three components are mainly shared by the artificial organelles: the membrane compartment separating the inner and outer parts, membrane proteins for proton translocation, and the molecular rotary machine for ATP synthesis. Depending on the initiation factors, they are further categorized into artificial mitochondrion and artificial chloroplasts, which use chemical nutrients for oxidative phosphorylation and light for photosynthesis, respectively. In this review, we summarize the essential components needed for artificial organelles and then review the recent progress on two different artificial organelles. Recent strategies, purified and identified proteins, and working principles are discussed. With more study on the artificial mitochondrion and artificial chloroplasts, they are expected to be very powerful tools, allowing us to achieve complex cascading reactions in artificial cells, like the ones that happen in real cells.

Engineering tunable terahertz radiation from an electron bunch using graphene metasurfaces.

We propose an approach to generate tunable terahertz (THz) radiation from an electron bunch passing over the unique graphene metasurface. We not only control the frequency of the THz radiation but also tune the amplitude and direction of the radiation by varying the chemical potential of the graphene. Several new phenomena are observed. The radiation has the same frequency with the resonant frequency of the graphene metasurface at normal incidence. The radiation frequency meets the linear relationship with the chemical potential. The radiation magnitude is the inverse to the reflection magnitude, and the sum of them is close to being a constant. The strong Smith-Purcell radiation on the graphene metasurface is due to the interaction between the electron bunch and periodic surface plasmon polaritons (SPPs). The stronger the SPP, the higher is the radiation magnitude that is obtained. These results would provide a promising way for developing tunable radiation in the THz band.

Clinical characteristics of 10 Chinese patients with melorheostosis and identification of a somatic MAP2K1 variant in one case.

BACKGROUND: Melorheostosis (MEL) is an exceptionally rare sclerosing bone dysplasia with asymmetrically exuberant bone formation and soft tissue lesions in a segmental distribution. We aimed to summarize the clinical characteristics of Chinese MEL patients and identify their pathogenic cause. METHODS: In total, 10 Chinese MEL patients were recruited, and clinical manifestations and radiological characteristics were recorded. Sanger sequencing of the LEMD3 gene was performed on peripheral blood samples of all patients, while the exome sequencing of matched peripheral blood, melorheostotic bone, and skin lesion samples was conducted on one patient who provided affected bone and skin tissues. Micro-computed tomography (micro-CT) was also used to scan the melorheostotic bone tissue. RESULTS: We found the average age of the 10 MEL patients was 29.5 years (range 11-40 years), and the major symptoms were bone pain, restricted movement, and bone deformity. The lesions sites were mainly located in femur (8/10), tibia (8/10), fibula (6/10), and foot (7/10), the next was pelvis (4/10), and the last were patella (1/10), hand (1/10) and spine (1/10). Radiological examinations showed a mixture of hyperostosis consisting of classic "dripping candle wax," "osteoma-like," or "myositis ossificans-like" patterns in most patients. No germline pathogenic variants in the LEMD3 gene were found in all patients, but a disease-causing somatic variant of MAP2K1 (c.167A > C, p.Gln56Pro) was detected in melorheostotic bone from one patient. Moreover, the micro-CT analysis showed increased porosity in the melorheostotic bone with somatic MAP2K1 variant. CONCLUSION: This is a summary of the clinical characteristics of Chinese MEL patients and we first identify the somatic MAP2K1 variant in Chinese patients. Our findings validate the molecular genetic mechanism of MEL and broaden its phenotype spectrum in the Chinese population.

Fe-VS2 Electrocatalyst with Organic Matrix-Mediated Electron Transfer for Highly Efficient Nitrogen Fixation.

Electrochemical N2 fixation is considered to be a promising alternative to Haber-Bosch technology. Inspired by the composition and structure of natural nitrogenase, Fe-doped VS2 nanosheets were prepared via one-step solvothermal method. The electron transfer system mediated by organic conductive polymer (1-AAQ-PA) was constructed to promote the electron transfer between Fe-VS2 nanosheets and the electrode in electrocatalytic N2 reduction reaction (NRR). The obtained 1-AAQ-PA-Fe-VS2 electrode converted N2 to NH3 with a yield of 31.6 µg h-1 mg-1 at -0.35 V vs. reversible hydrogen electrode and high faradaic efficiency of 23.5 %. The introduction of Fe dopants favored N2 adsorption and activation, while the Li-S bond between Fe-VS2 and Li2 SO4 effectively inhibited hydrogen evolution. The highly efficient electron utilization in the electrocatalytic NRR process was realized using the 1-AAQ-PA as the electron transfer medium. Density functional theory calculations showed that N2 was preferentially adsorbed on Fe and reduced to NH3 via both distal and alternating mechanism.

Progress on Crowding Effect in Cell-like Structures.

Several biological macromolecules, such as proteins, nucleic acids, and polysaccharides, occupy about 30% of the space in cells, resulting in a crowded macromolecule environment. The crowding effect within cells exerts an impact on the functions of biological components, the assembly behavior of biomacromolecules, and the thermodynamics and kinetics of metabolic reactions. Cell-like structures provide confined and independent compartments for studying the working mechanisms of cells, which can be used to study the physiological functions arising from the crowding effect of macromolecules in cells. This article mainly summarizes the progress of research on the macromolecular crowding effects in cell-like structures. It includes the effects of this crowding on actin assembly behavior, tubulin aggregation behavior, and gene expression. The challenges and future trends in this field are presented at the end of the paper.

Reversible Deformation of Artificial Cell Colonies Triggered by Actin Polymerization for Muscle Behavior Mimicry.

The use of artificial cells to mimic living tissues is beneficial for understanding the mechanism of interaction among cells. Artificial cells hold immense potential in the field of tissue engineering. Self-powered artificial cells capable of reversible deformation are developed by encapsulating living mitochondria, actins, and methylcellulose. Upon addition of pyruvate molecules, the mitochondria produce adenosine triphosphate (ATP), which acts as an energy source to trigger actin polymerization. The reversible deformation of artificial cells occurs with a spindle shape resulting from the polymerization of actins to form filaments adjacent to the lipid bilayer that subsequently returns to a spherical shape resulting from the depolymerization of actin filaments upon laser irradiation. The linear colonies composed of these artificial cells exhibit collective contraction and relaxation to mimic muscle tissues. At maximum contraction, the long axis of each giant unilamellar vesicle (GUV) is parallel to each other. All the colonies are synchronized in the contraction phase. The deformation of each GUV in the colonies is influenced by its adjacent GUVs. The muscle-like artificial cell colonies described here pave the way to develop sustainably self-powered artificial tissues.

RGD Peptide Modified Erythrocyte Membrane/Porous Nanoparticles Loading Mir-137 for NIR-Stimulated Theranostics of Glioblastomas.

Cell-derived drug carriers have increasingly gained the interest of the scientific community due to their ability to imitate various natural properties of their source cells. We developed theranostics nanoplatforms composed of mesoporous silica nanoparticles (MSNs), indocyanine green (ICG) molecules, microRNAs-137 (miR-137), red-blood-cell membranes (RM), and tumor-targeting cyclo Arg-Gly-Asp-d-Phe-Cys peptides (cRGD(fC)), which were abbreviated as MSNs/ICG/miR/RM/RGD particles. These particles possessed photothermal and gene therapy properties due to ICG and miR-137, respectively. The photothermal conversion efficiency was ~18.7%. Upon 808 nm light irradiation, the tumor inhibition rate reached 94.9% with dosage of 10 mg/kg. The developed nanoplatform possessed unique properties, such as exceptional biocompatibility, immune escaping, and specific recognition, which was also used for near-infrared fluorescence, photoacoustic (PA) bimodal imaging-guided tumor recognition.

Erratum: Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.

[This corrects the article on p. 11814 in vol. 13, PMID: 34786110.].

High-throughput production of functional prototissues capable of producing NO for vasodilation.

Bottom-up synthesis of prototissues helps us to understand the internal cellular communications in the natural tissues and their functions, as well as to improve or repair the damaged tissues. The existed prototissues are rarely used to improve the function of living tissues. We demonstrate a methodology to produce spatially programmable prototissues based on the magneto-Archimedes effect in a high-throughput manner. More than 2000 prototissues are produced once within 2 h. Two-component and three-component spatial coded prototissues are fabricated by varying the addition giant unilamellar vesicles order/number, and the magnetic field distributions. Two-step and three-step signal communications in the prototissues are realized using cascade enzyme reactions. More importantly, the two-component prototissues capable of producing nitric oxide cause vasodilation of rat blood vessels in the presence of glucose and hydroxyurea. The tension force decreases 2.59 g, meanwhile the blood vessel relaxation is of 31.2%. Our works pave the path to fabricate complicated programmable prototissues, and hold great potential in the biomedical field.

Micrometer-size double-helical structures from phospholipid-modified carbon nanotubes.

Biomolecular self-assembly plays a key role in the life system. Herein, double-helical phospholipid-modified carbon nanotube structures were constructed via the self-assembly of phospholipids on carbon nanotubes. These micrometer size spring structures may find potential applications in biocompatible microrobots.

Mimicking Cellular Metabolism in Artificial Cells: Universal Molecule Transport across the Membrane through Vesicle Fusion.

Mass transport across cell membranes is a primary process for cellular metabolism. For this purpose, electrostatically mediated membrane fusion is exploited to transport various small molecules including glucose-6-phosphate, isopropyl ß-D-thiogalactoside, and macromolecules such as DNA plasmids from negatively charged large unilamellar vesicles (LUVs) to positively charged giant unilamellar vesicles (GUVs). After membrane fusion between these oppositely charged vesicles, molecules are transported into GUVs to trigger the NAD+ involved enzyme reaction, bacterial gene expression, and in vitro gene expression of green fluorescent protein from a DNA plasmid. The optimized charged lipid percentages are 10% for both positively charged GUVs and negatively charged LUVs to ensure the fusion process. The experimental results demonstrate a universal way for mass transport into the artificial cells through vesicle fusions, which paves a crucial step for the investigation of complicated cellular metabolism.