Exosomes are becoming an important mediator of the interaction between tumor cells and the microenvironment. Ferroptosis is a newly discovered type of cell death. However, its role in the progression of liver cancer is largely unknown. The aim of the presents study was to analyze the mechanism by which hepatitis B virus (HBV)-positive liver cancer secretes exosomes to mediate the iron death of M1 macrophages, thereby promoting the development of liver cancer.

Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency. Herein, we constructed a nanocomposite based on gold nanorods (GNRs) and drug-loaded tetrahedral DNA nanostructures (TDN) for chemo-photothermal combinational therapy. Anti-tumor drug doxorubicin (DOX) was loaded via the insertion within GC base pairs of TDN. The aptamer AS1411 was attached to the apex of TDN (ATDN) to target tumor cells. The DOX-loaded DNA tetrahedron (ATDN-DOX) was compressed by the GNRs coated with PEI (GNRs@ATDN-DOX) to realize the photothermal function and lysosome escape. GNRs under the illumination of 808 nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer. The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN. The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape. The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.

Hollow microneedle patches (HMNPs) have great promise for efficient and precise transdermal drug delivery in a painless manner. Currently, the clinical application of HMNPs is restricted by its complex manufacturing processes. Here, we use a new three-dimensional (3D) printing technology, static optical projection lithography (SOPL), for the fast fabrication of HMNPs. In this technology, a light beam is modulated into a customized pattern by a digital micromirror device (DMD) and projected to induce the spatial polymerization of monomer solutions which is controlled by the distribution of the light intensity in the monomer solutions. After an annulus picture is inputted into the DMD via the computer, the microneedles with hollow-cone structure can be precisely printed in seconds. By designing the printing pictures, the personalized HMNPs can be fast customized, which can afford the scale-up preparation of personalized HMNPs. Meanwhile, the obtained hollow microneedles (HMNs) have smooth surface without layer-by-layer structure in the commonly 3D-printed products. After being equipped with a micro-syringe, the HMNPs can efficiently deliver insulin into the skin by injection, resulting in effective control of the blood glucose level in diabetic mice. This work demonstrates a SOPL-based 3D printing technology for fast customization of HMNPs with promising medical applications.

While the installation of complex genetic circuits in microorganisms is relatively routine, the synthetic biology toolbox is severely limited in plants. Of particular concern is the absence of combinatorial analysis of regulatory elements, the long design-build-test cycles associated with transgenic plant analysis, and a lack of naming standardization for cloning parts. Here, we use previously described plant regulatory elements to design, build, and test 91 transgene cassettes for relative expression strength. Constructs were transiently transfected into Nicotiana benthamiana leaves and expression of a fluorescent reporter was measured from plant canopies, leaves, and protoplasts isolated from transfected plants. As anticipated, a dynamic level of expression was achieved from the library, ranging from near undetectable for the weakest cassette to a ∼200-fold increase for the strongest. Analysis of expression levels in plant canopies, individual leaves, and protoplasts were correlated, indicating that any of the methods could be used to evaluate regulatory elements in plants. Through this effort, a well-curated 37-member part library of plant regulatory elements was characterized, providing the necessary data to standardize construct design for precision metabolic engineering in plants.

Caloric restriction is a robust intervention to increase lifespan. Giving less food (calorie restriction [CR]) or allowing free access to a diluted diet with indigestible components (calorie dilution [CD]) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compare responses of C57BL/6 mice with equivalent levels of CR and CD. The two groups have different responses in fat loss, circulating hormones, and metabolic rate. CR mice are hungrier, as assessed by behavioral assays. Although gene expression of Npy, Agrp, and Pomc do not differ between CR and CD groups, CR mice had a distinctive hypothalamic gene-expression profile with many genes related to starvation upregulated relative to CD. While both result in lower calorie intake, CR and CD are not equivalent procedures. Increased hunger under CR supports the hypothesis that hunger signaling is a key process mediating the benefits of CR.

To assess the pain and function of acupuncture in patients with nonspecific low back pain (NSLBP).

Polyploidy varieties have been reported to exhibit higher stress tolerance relative to their diploid relatives, however, the underlying molecular and physiological mechanisms remain poorly understood. In this study, a batch of autotetraploid Citrus wilsonii were identified from a natural seedling population, and these tetraploid seedlings exhibited greater tolerance to drought stress than their diploids siblings. A global transcriptome analysis revealed that a large number of genes involved in photosynthesis response were enriched in tetraploids under drought stress, which was consistent with the changes in photosynthetic indices including Pn, gs, Tr, Ci, and chlorophyll contents. Compared with diploids, phosphorylation was also modified in the tetraploids after drought stress, as detected through tandem mass tag (TMT)-labeled proteomics. Additionally, tetraploids prioritized the regulation of plant hormone signal transduction at the transcriptional level after drought stress, which was also demonstrated by increased levels of IAA, ABA, and SA and reduced levels of GA3 and JA. Collectively, our results confirmed that the synergistic regulation of photosynthesis response, phosphorylation modification and plant hormone signaling resulted in drought tolerance of autotetraploid C. wilsonii germplasm.

Severe coronavirus disease 2019 (COVID -19) has led to a rapid increase in mortality worldwide. Rheumatoid arthritis (RA) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the molecular mechanisms underlying RA and CVOID-19 are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19 and RA using bioinformatics and a systems biology approach.

To date, little is known about the evolution of fern genomes, with only two small genomes published from the heterosporous Salviniales. Here we assembled the genome of Alsophila spinulosa, known as the flying spider-monkey tree fern, onto 69 pseudochromosomes. The remarkable preservation of synteny, despite resulting from an ancient whole-genome duplication over 100 million years ago, is unprecedented in plants and probably speaks to the uniqueness of tree ferns. Our detailed investigations into stem anatomy and lignin biosynthesis shed new light on the evolution of stem formation in tree ferns. We identified a phenolic compound, alsophilin, that is abundant in xylem, and we provided the molecular basis for its biosynthesis. Finally, analysis of demographic history revealed two genetic bottlenecks, resulting in rapid demographic declines of A. spinulosa. The A. spinulosa genome fills a crucial gap in the plant genomic landscape and helps elucidate many unique aspects of tree fern biology.

Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation.

Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness.

How decisions are made when autonomous vehicles (AVs) are faced with moral dilemmas is still a challenge. For this problem, this paper proposed the concept of common principles, which were drawn from the general public choice and could be generally accepted by society. This study established five moral dilemma scenarios with variables including the number of sacrifices, passenger status, presence of children, decision-making power subjects, and laws. Based on existing questionnaire data, we used gray correlation analysis to analyze the influence of the individual and psychological factors of participants in decision-making. Then, an independent sample t-test and analysis of covariance were selected to analyze the influence relationship between individual and psychological factors. Finally, by induction statistics of decision choices and related parameters of participants, we obtain common principles of autonomous vehicles, including the principle of protecting law-abiding people, the principle of protecting the majority, and the principle of protecting children. The principles have different priorities in different scenarios and can meet the complex changes in moral dilemmas. This study can alleviate the contradiction between utilitarianism and deontology, the conflict between public needs and individualized needs, and it can provide a code of conduct for ethical decision-making in future autonomous vehicles.

The transformation of organic pollutants by stabilized nano-FeS in oxic conditions is far less understood than in anoxic states. Herein, carboxymethyl cellulose-stabilized FeS (CMC-FeS) nanofluids are prepared at a CMC-to-FeS mass ratio of 1/2 and their performance of tetracycline hydrochloride (TC) degradation under oxic conditions was investigated. Here, we showed that TC could be efficiently removed by oxygenation of CMC-FeS nanofluids at neutral initial pH. We found that CMC-FeS dosages as low as 15 mg/L can achieve the TC removal efficiency as high as 99.1% at an initial TC concentration of 50 mg/L. Oxidative degradation plays a predominated role in TC removal (accounting for 58.0%), adsorption has the second importance (accounting for 37.0%), and reduction has minor impact (accounting for 4.1%) toward TC removal. Electron spin resonance assays, fluorescent detection using coumarin as a probe, and radical scavenging experiments confirm that hydroxy radicals (•OH), both in free and surface-bound forms, contribute to oxidation of TC. Humic acids brought detrimental effects on TC removal and therefore should be biologically degraded in advance. This work offers a facile and cost-effective solution to decontaminate TC in natural and engineered water bodies.

Acute Lung Injury (ALI) due to inhaled pathogens causes high mortality. Underlying mechanisms are inadequately understood. Here, by optical imaging of live mouse lungs we show that a key mechanism is the viability of cytosolic Ca2+ buffering by the mitochondrial Ca2+ uniporter (MCU) in the lung's surfactant-secreting, alveolar type 2 cells (AT2). The buffering increased mitochondrial Ca2+ and induced surfactant secretion in wild-type mice, but not in mice with AT2-specific MCU knockout. In the knockout mice, ALI due to intranasal LPS instillation caused severe pulmonary edema and mortality, which were mitigated by surfactant replenishment prior to LPS instillation, indicating surfactant's protective effect against alveolar edema. In wild-type mice, intranasal LPS, or Pseudomonas aeruginosa decreased AT2 MCU. Loss of MCU abrogated buffering. The resulting mortality was reduced by spontaneous recovery of MCU expression, or by MCU replenishment. Enhancement of AT2 mitochondrial buffering, hence endogenous surfactant secretion, through MCU replenishment might be a therapy against ALI.

Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.

Laryngeal cancer is one of the highest incidence, most prevalently diagnosed head and neck cancers, making it critically necessary to probe effective targets for laryngeal cancer treatment. Here, real-time quantitative reverse transcription PCR (qRT-PCR) and western blot analysis were used to detect gene expression levels in laryngeal cancer cell lines. Fluorescence in situ hybridization (FISH) and subcellular fractionation assays were used to detect the subcellular location. Functional assays encompassing Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were performed to examine the effects of target genes on cell proliferation and migration in laryngeal cancer. The in vivo effects were proved by animal experiments. RNA-binding protein immunoprecipitation (RIP), RNA pulldown and luciferase reporter assays were used to investigate the underlying regulatory mechanisms. The results showed that KIF26B antisense RNA 1 (KIF26B-AS1) propels cell proliferation and migration in laryngeal cancer and regulates the toll-like receptor 4 (TLR4) signaling pathway. KIF26B-AS1 also recruits FUS to stabilize TLR4 mRNA, consequently activating the TLR4 signaling pathway. Furthermore, KIF26B-AS1 plays an oncogenic role in laryngeal cancer via upregulating TLR4 expression as well as the FUS/TLR4 pathway axis, findings which offer novel insight for targeted therapies in the treatment of laryngeal cancer patients.

Acinetobacter baumannii is an important nosocomial pathogen. Upon colonizing a host, A. baumannii are subjected to selective pressure by immune defenses as they adapt to the host environment. However, the mechanism of this pathoadaptation is unknown. Here, we established an in vitro system to evolve A. baumannii driven by the continuous selective pressure exerted by epithelial cells, and we used a combination of experimental evolution, phenotypic characterization and multi-omics analysis to address the underlying mechanism. When continuously exposed to selective pressure by pulmonary epithelial cells, A. baumannii showed ptk mutation-mediated mucoid conversion (reduced adhesion and increased anti-phagocytic ability) by enhancement of capsular exopolysaccharide chain length; rsmG mutation-mediated deficiency of 7-methylguanosine modification in the 524th nucleotide of 16S rRNA, which increased ribosome translation efficiency; and rnaseI mutation-mediated changes in outer membrane permeability and efflux pump expression. Together, these mutations altered susceptibility to a variety of antimicrobial agents, including the novel antibiotic cefiderocol, by regulating siderophore and siderophore-receptor biosynthesis. In conclusion, pulmonary epithelial cells modulate A. baumannii pathoadaptation, implicating the host-microbe interaction in the survival and persistence of A. baumannii.

Cachexia is characterized by progressive weight loss accompanied by the loss of specific skeletal muscle and adipose tissue. Increased lactate production, either due to the Warburg effect from tumors or accelerated glycolysis effects from cachectic muscle, is the most dangerous factor for cancer cachexia. This study aimed to explore the efficiency of 2-deoxy-D-glucose (2-DG) in blocking Cori cycle activity and its therapeutic effect on cachexia-associated muscle wasting. A C26 adenocarcinoma xenograft model was used to study cancer cachectic metabolic derangements. Tumor-free lean mass, hindlimb muscle morphology, and fiber-type composition were measured after in vivo 2-DG administration. Activation of the ubiquitin-dependent proteasome pathway (UPS) and autophagic-lysosomal pathway (ALP) was further assessed. The cachectic skeletal muscles of tumor-bearing mice exhibited altered glucose and lipid metabolism, decreased carbohydrate utilization, and increased lipid β-oxidation. Significantly increased gluconeogenesis and decreased ketogenesis were observed in cachectic mouse livers. 2-DG significantly ameliorated cancer cachexia-associated muscle wasting and decreased cachectic-associated lean mass levels and fiber cross-sectional areas. 2-DG inhibited protein degradation-associated UPS and ALP, increased ketogenesis in the liver, and promoted ketone metabolism in skeletal muscle, thus enhancing mitochondrial bioenergetic capacity. 2-DG effectively prevents muscle wasting by increasing ATP synthesis efficiency via the ketone metabolic pathway and blocking the abnormal Cori cycle.

C-reactive protein (CRP) has been shown to be a potential candidate target in the immunotherapy of severe influenza A infection. However, it is unclear on the pathogenesis associated with CRP in influenza infections. Here, we used influenza A H1N1 CA04 to infect human CRP transgenic mice (KI), CRP knockout mice (KO), and wild-type mice (WT), respectively, and compared the viral pathogenicity and associated immune response in those mice. The results showed that CA04 infection resulted in 100%, 80%, and 60% death in KO, KI, and WT mice, respectively. Compared to WT mice, CA04 infection resulted in higher TCID50 in lungs on day 3 after infection but lowered HI antibody titers in sera of survivors on day 21 after infection in KI mice. ELISA assay showed that IFN-γ concentration was significantly increased in sera of WT, KI, or KO mice on day 7 after infection, and IL-17 was remarkably increased in sera of WT mice but decreased in sera of KI mice while no significant change in sera of KO mice on day 3 or 7 after infection. Quantitative RT-PCR showed that the relative expression levels of immune checkpoint CTLA-4, LAIR-1, GITR, BTLA, TIM-3, or PD-1 mRNA in the lung presented decreased levels on day 3 or 7 after infection in KI or KO mice. The correlation analysis showed that mRNA expression levels of the 6 molecules positively correlated with viral TICD50 in WT mice but negatively correlated with viral TCID50 in KI or KO mice. However, only LAIR-1 presented a significant correlation in each lung tissue of WT, KI, or KO mice with CA07 infection statistically. IHC results showed that LAIR-1 positive cells could be found in WT, KO, or KI mice lung tissues with CA04 infection, and the positive cells were mainly distributed in an inflammatory dense area. Our results suggested that deficiency of CRP or human CRP transgenic treatment aggravates influenza A virus infection in mice. CRP is a double sword in immune regulation of influenza infection in which IL-17 and immune checkpoint may be involved.

Medical education assessments are becoming more complex, resulting in the inappropriateness of traditional methods primarily consisting of direct observations, oral examinations, and multiple-choice tests. Advancements in research methods have led to the formation of new modalities, namely performance assessments, which are, on the other hand, always costly in development and implementation. Proposing using the Program Effectiveness and Cost Generalization flow within an assessment context (PRECOG-A), this brief report explores the real financial cost drivers associated with an assessment case in the context of medical education, presents the steps in bridging the effectiveness with its psychometric properties via cost-effectiveness analysis, and evaluates the two-side outcomes for further evaluation decision-making. Referentially providing a framework to investigators and researchers, the illustration of PRECOG-A in this study outlines instructional guidelines for conducting cost-effectiveness analysis in a performance assessment.