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Abstract Motile cilia unify their axonemal orientations (AOs), or beat directions, across epithelia to drive liquid flows. This planar polarity results from cytoskeleton-driven swiveling of basal foot (BF), a basal body (BB) appendage coincident with the AO, in response to regulatory cues. How and when the BF-AO relationship is established, however, are unaddressed. Here, we show that the BF-AO coupling occurs during rotational polarizations of BBs and requires Ccdc57. Ccdc57 localizes on BBs as a rotationally-asymmetric punctum, which polarizes away from the BF in BBs having achieved the rotational polarity to probably fix the BF-AO relationship. Consistently, Ccdc57-deficient ependymal multicilia lack the BF-AO coupling and display directional beats at only single cell level. Ccdc57 −/− tracheal multicilia also fail to fully align their BFs. Furthermore, Ccdc57 −/− mice manifest severe hydrocephalus, due to impaired cerebrospinal fluid flow, and high mortality. These findings unravel mechanisms governing the planar polarity of epithelial motile cilia.

Abstract Intercropping systems have garnered attention as a sustainable agricultural approach for efficient land use, increased ecological diversity in farmland, and enhanced crop yields. This study examined the effect of intercropping on the kiwifruit rhizosphere to gain a deeper understanding of the relationships between cover plants and kiwifruit in this sustainable agricultural system. Soil physicochemical properties and bacterial communities were analyzed using the Kiwifruit-Agaricus blazei intercropping System. Moreover, a combined analysis of 16S rRNA gene sequencing and metabolomic sequencing was used to identify differential microbes and metabolites in the rhizosphere. Intercropping led to an increase in soil physicochemical and enzyme activity, as well as re-shaping the bacterial community and increasing microbial diversity. Proteobacteria, Bacteroidota, Myxococcota, and Patescibacteria were the most abundant and diverse phyla in the intercropping system. Expression analysis further revealed that the bacterial genera BIrii41, Acidibacter, and Altererythrobacter were significantly upregulated in the intercropping system. Moreover, 358 differential metabolites (DMs) were identified between the monocropping and intercropping cultivation patterns, with fatty acyls, carboxylic acids and derivatives, and organooxygen compounds being significantly upregulated in the intercropping system. The KEGG metabolic pathways further revealed considerable enrichment of DMs in ABC transporters, histidine metabolism, and pyrimidine metabolism. This study identified a significant correlation between 95 bacterial genera and 79 soil metabolites, and an interactive network was constructed to explore the relationships between these differential microbes and metabolites in the rhizosphere. This study demonstrated that Kiwifruit-Agaricus blazei intercropping can be an effective, labor-saving, economic, and sustainable practice for reshaping bacterial communities and promoting the accumulation and metabolism of beneficial microorganisms in the rhizosphere.

Plant-derived exosome-like nanoparticles (ELNs) have demonstrated cross-kingdom capabilities in regulating intercellular communication, facilitating drug delivery, and providing therapeutic interventions in humans. However, the functional attributes of konjac-derived ELNs (K-ELNs) remain largely unexplored. This study investigates the isolation, characterization, and functional analysis of K-ELNs, along with the profiling and differential expression analysis of associated miRNAs in both K-ELNs and Konjac tissues. K-ELNs were successfully isolated and characterized from two konjac species using ultracentrifugation, followed by Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA). Small RNA sequencing identified a total of 3,259 miRNAs across all samples. Differential expression analysis revealed significant differences in miRNA profiles between K-ELNs and tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of target genes provided insights into their roles in modulating pathways associated with diseases such as cancer and neurodegenerative disorders. Additionally, six miRNAs were selected for validation of sequencing results via RT-qPCR. The 5’RLM-RACE method was employed to validate the cleavage sites between differentially expressed miRNAs (DEMs) and their predicted target genes, further substantiating the regulatory roles of miRNAs in konjac. The findings of this study enhance our understanding of the molecular mechanisms underlying the biological functions and applications of K-ELNs, laying the groundwork for future research into their potential therapeutic roles in human health.

Optical vortices (OV) with an open shape have a unique function in directional particle transport and collection. A power-exponent-phase vortex (PEPV) has received particular attention as a type of unconventional vortex beam with a large opening and carrying orbital angular momentum (OAM). So far, only the generation methods and properties of an individual PEPV beam have been studied and analyzed. In this paper, we use dielectric metasurfaces instead of the conventional bulky optical device to generate PEPV arrays with a uniform diffracted intensity distribution and a controllable correlation between the topological charge number and the diffraction order. This approach is based on the theory of PEPV and combined with the principle of Dammann grating. The proposed method provides a new platform for various applications of light-matter interactions such as optical communication, optical encryption, and multi-particle manipulation.

Abstract Background Cytochrome P450 (Cytochrome P450s) genes are involved in the catalysis of various reactions, including growth, development, and secondary metabolite biosynthetic pathways. However, little is known about the characteristics and functions of the P450 gene family in Camellia sinensis (C. sinensis). Results To reveal the mechanisms of tea plant P450s coping with abiotic stresses, analyses of the tea plant P450 gene family were conducted using bioinformatics-based methods. In total, 273 putative P450 genes were identified from the genome database of C. sinensis. The results showed that P450s were well-balanced across the chromosomes I to XV of entire genome, with amino acid lengths of 268–612 aa, molecular weights of 30.95–68.5 kDa, and isoelectric points of 4.93–10.17. Phylogenetic analysis divided CsP450s into 34 subfamilies, of which CYP71 was the most abundant. The predicted subcellular localization results showed that P450 was distributed in a variety of organelles, with chloroplasts, plasma membrane,,and cytoplasm localized more frequently. The promoter region of CsP450s contained various cis-acting elements related to phytohormones and stress responses. In addition, ten conserved motifs (Motif1-Motif10) were identified in the CsP450 family proteins, with 27 genes lacking introns and only one exon. The results of genome large segment duplication showed that there were 37 pairs of genes with tandem duplication. Interaction network analysis showed that CsP450 could interact with multiple types of target genes, and there are protein interactions within the family. Tissue expression analysis showed that P450 was highly expressed in roots and stems. Moreover, qPCR analysis of the relative expression level of the gene under drought and cold stress correlated with the sequencing results. Conclusions This study lays the foundation for resolving the classification and functional study of P450 family genes and provides a reference for the molecular breeding of C. sinensis.

Context Substantial evidence suggests that ovarian oxidative stress can result in severe ovarian dysfunction.Objective The purpose of this article is to investigate the potential of SIRT6 in alleviating premature ovarian failure (POF) by inhibiting oxidative stress.Methods To mimic POF, mice were administered daily subcutaneous injections of d-galactose. The levels of E2, FSH, LH, AMH, and progesterone in serum were measured, along with changes in follicles and SIRT6 levels. Mice were treated with the SIRT6 agonist MDL-800, SIRT6 levels, follicles, and aforementioned hormones were reassessed. The effects of MDL-800 on oxidative stress and apoptosis were subsequently identified. Primary granulosa cells were isolated from mice, and the effects of H2O2 and MDL-800 on cell viability, oxidative stress, SIRT6 level, and apoptosis were evaluated. In addition, the regulation of SIRT6 on H3K9AC/p66SHC was verified by examining changes in protein levels, promoter activity, and the reversal effects of p66SHC overexpression.Results MDL-800 mitigated hormone fluctuations, reduced follicle depletion in ovarian tissue, and attenuated oxidative stress and apoptosis in mice. In vitro experiments demonstrated that MDL-800 enhanced the resilience of primary granulosa cells against H2O2, as evidenced by increased cell viability and reduced oxidative stress and apoptosis. Furthermore, SIRT6 was found to decrease H3K9AC and p66SHC levels, as well as attenuate p66SHC promoter activity. The protective effects of MDL-800 on cells were reversed upon p66SHC overexpression.Conclusion In summary, this study highlights that activation of SIRT6 can alleviate POF and reduce oxidative stress by degrading H3K9AC and suppressing p66Shc levels in granulosa cells.

Acute graft versus host disease is a rare but deadly complication following liver transplantation. Author show here, upon screening a large cohort of liver transplanted patients and detailed immune phenotyping of samples from the 7 affected individuals and appropriate controls, that human T cell lymphotropic virus type I infection of donor immune cells appear to correlate with the occurrence of acute graft versus host disease.

The main problem faced by traditional three-dimensional (3D) holographic displays is the time-consuming and poor flexibility of the hologram generation process. To address this issue, this paper proposes a non-iterative 3D computer-generated hologram (SFS-ORAP-PC-3D) method based on single full-support optimized random phase and phase compensation. Combining the full-support optimized random phase (FS-ORAP) method and the 3D layer-based idea to efficiently and non-iteratively generate the phase-only hologram of a 3D object with arbitrary positions and sizes using single FS-ORAP, thus overcoming the limitations of the original ORAP method in target position and size. Meanwhile, using a Fresnel lens for phase compensation allows for free selection of reconstruction planes. Numerical and optical experiments validate the feasibility of our proposed method.

Cryptococcosis infection after transplantation is easily overlooked or misdiagnosed. We report a cluster of donor-derived cryptococcosis infection in liver and kidney transplant recipients from the same donor in China. Infections occurred within 1 month after transplantation, and were confirmed by using biopsies and blood tests.

Abstract. Invasive pulmonary aspergillosis (IPA) is a lethal infectious disease with high mortality in patients with liver failure. Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes. Voriconazole is recommended as the first-line drug for IPA, but hepatotoxicity limits its use in the context of liver diseases. We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure. The polymorphism of cytochrome P450 (CYP) isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole. However, the patient developed side effects such as skin rash, vomiting, hyperbilirubinemia, and alteration of consciousness, even if she received half of the recommended dosage for voriconazole. Therapeutic drug monitoring (TDM) was applied to guide the dosage adjustment of voriconazole in this patient, and consequently, the patient presented a favorable outcome. In conclusion, genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.

Abstract HgCdTe avalanche photodiodes promise various fascinating applications due to the outstanding capability of detecting weak signals or even single photon. However, the underlying transport mechanisms of diverse dark current components are still unresolved at high reverse bias, thus limiting the development of high-performance devices. Here, we establish an accurate model to demonstrate the competitive mechanism between band-to-band and avalanche dark currents in positive-intrinsic-negative structures. Based on the high consistency between the simulated and measured results, we find that both components jointly dominate overall dark current but with a larger avalanche current. This breaks the conventional cognition that band-to-band dark current contributes the majority. With the guidance, we reconstruct an optimized device and achieve gain 1876 (6153) and dark current 10−10 (10−9) A at bias −10 (−10.5) V, respectively. Comparisons of dark current and gain with reported single-element devices further confirm the outstanding performance of our device.

BackgroundHepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) have conventionally been regarded as a contraindication for liver transplantation (LT). However, the outcomes of deceased donor liver transplantation (DDLT) in patients with segmental PVTT remain unknown. The aim of this study is to evaluate the feasibility and effectiveness of DDLT in the treatment of HCC with segmental PVTT.MethodsWe retrospectively analyzed 254 patients who underwent DDLT for HCC in our institution from January 2015 to November 2019. To assess the risks of PVTT, various clinicopathological variables were evaluated. Overall (OS) and recurrence-free survival (RFS) analyses based on different PVTT types were performed in HCC patients.ResultsOf the 254 patients, a total of 46 patients had PVTT, of whom 35 had lobar PVTT and 11 had segmental PVTT in second-order branches or below. Alpha-fetoprotein (AFP) level, tumor maximal diameter, histological grade, micro-vascular invasion (MVI), RFS, and OS were significantly different between the control and PVTT groups. Lobar PVTT was associated with unfavorable 5-year RFS and OS compared with MVI group (28.6% and 17.1%, respectively). Instead, no significant difference was observed between the segmental PVTT and MVI group in terms of 5-year RFS and OS (RFS: 36.4% vs. 40.4%, p=0.667; OS: 54.5% vs. 45.1%, p=0.395). Further subgroup analysis showed segmental PVTT with AFP levels ≤100 ng/ml presented significantly favorable RFS and OS rates than those with AFP level >100 ng/ml (p=0.050 and 0.035, respectively).ConclusionsIn summary, lobar PVTT remains a contraindication to DDLT. HCC patients with segmental PVTT and AFP level ≤100 ng/ml may be acceptable candidates for DDLT.

Background and aims: The exact function of Phosphatidylinositol Glycan Anchor Biosynthesis, Class C (PIGC) gene has yet to be elucidated. In the study, we attempted to clarify the correlations of PIGC to prognosis and tumor-infiltrating lymphocytes in hepatocellular carcinoma (HCC).Methods:PIGC expression was analyzed via the Oncomine database, Gene Expression Profiling Interactive Analysis, Hepatocellular carcinoma data base, Human Protein Atlas database and Tumor Immune Estimation Resource (TIMER). We showed the correlation of PIGC with the clinical characteristics using UALCAN. We evaluated the influence of PIGC on clinical prognosis using Kaplan-Meier plotter databases. And co-expressed genes with PIGC and its regulators were identified using LinkedOmics. The correlations between PIGC and cancer immune infiltrates were investigated via TIMER. We analyzed the drug sensitivity and immunotherapy response via R package.Results:PIGC was found up-regulated in tumor tissues in multiple HCC cohorts, also increased in HCC patient with different clinical characteristics. High PIGC expression was associated with poorer overall survival. PIGC expression showed a strong positive association with the expression of ACBD6, a strong negative association with AGXT212. The cell components and distribution in treatment and non-treatment of HCC patients were quite distinct, which may reveal the relationship between the immunotherapy with tumor microenvironment. Notably, PIGC expression was positively correlated with infiltrating levels of immune cells.Conclusion: These findings suggest that PIGC is correlated with prognosis and immune infiltrating in HCC, which can be used as a prognostic biomarker for determining prognosis, laying a foundation for further study of the immune regulatory role of PIGC in HCC.

As artificially designed two-dimensional (2D) arrays of subwavelength nanostructures, metasurfaces provide a new avenuefor the design of static planar optics. However, one would prefer a dynamic modulation of the metasurface in the event of practical applications. As a potentially important technique for information security, meta-holographic encryption has the characteristics of subwavelength pixels, precise control, and high safety factor. In this paper, by integrating birefringent liquid crystals (LCs) with all-dielectric metasurfaces in combination with visual cryptography (VC), we demonstrate a tunable metasurface with an information encryption function in the visible range. In the encryption process, the secret image is hidden in a set of unidentifiable and orthogonal arranged phase-only meta-holograms with high security of concealment. In the decryption process, the generated meta-hologram is illuminated by a plane wave and an electric field across the LC layer is applied to superimpose the reconstructed holographic patterns, thus we could acquire the secret image. Therefore, the decryption method can be flexibly and sufficiently adjusted with applied field under monitorable condition. For this reason, it is useful in enhancing the diversity of information hiding methods and improving the security of information. Our method can be extended to other similar applications.

In a classical metasurface-based holographic display system, a clear holographic reconstruction image can be obtained only in the back-focal-plane of the lens. However, when the receiving plane deviates from the focal plane, the reconstructed holographic image suffers from degradations that limit the quality of the images. Hence, we propose a novel metasurface-based holographic display to realize clearly continuous imaging within the specified position range by superimposing the meta-axilens phase. It can effectively relieve the alignment requirements of the imaging system. Firstly, the parameters and properties of all-dielectric meta-atom is analyzed. Then we compare and demonstrate two sets of metasurface-based optical elements (meta-axicon, meta-lens, and meta-axilens), made by silicon meta-atoms working at 610 nm. Furthermore, we show that the metasurface hologram with the axilens phase can form a series of the relatively clear holographic images away from the focal plane. Our proposal suggests a method to reconstruct holographic wavefront in different planes simultaneously, and one can find their application domain, such as 3D biological imaging, spectroscopy, optical information storage, and encryption.

ObjectiveTo investigate the efficacy of xuebijing combined with ulinastatin in the treatment of traumatic sepsis and analyze the effects on inflammatory factors and immune function of patients.Methods182 patients with traumatic sepsis were selected from June 2017 to September 2021 in our hospital. The patients were divided into the control group and the observation group. Patients in both groups were given routine treatments such as initial resuscitation, blood transfusion, monitoring of lactic acid to guide fluid replacement, early control of infection source, selection of appropriate antibiotics, correction of acidosis, treatment of primary disease, prevention of hypothermia and stress ulcer, application of vasoactive drugs, application of glucocorticoid and nutritional support. The control group was treated with Xuebijing injection on the basis of routine treatment, and the observation group was given Xuebijing injection combined with ulinastatin treatment on the basis of routine treatment. The APACHE II score was applied to evaluate the patients before and after treatment, and the routine blood indicators, inflammatory factor indicators, immune function indicators and liver function indicators were tested.ResultsAfter the treatment, the APACHE II score of the observation group was (10.35 ± 3.04) lower than that of the control group (15.93 ± 4.52) (P

Abstract Background Wheat yellow dwarf virus disease is infected by barley yellow dwarf virus (BYDV), which causes leaf yellowing and dwarfing symptoms in wheat, thereby posing a serious threat to China's food production. The infection of plant viruses can produce large numbers of vsiRNAs, which can target host transcripts and cause symptom development. However, few studies have been conducted to explore the role played by vsiRNAs in the interaction between BYDV-GAV and host wheat plants. Methods In this study, small RNA sequencing was conducted to profile vsiRNAs in BYDV-GAV-infected wheat plants. The putative targets of vsiRNAs were predicted by the bioinformatics software psRNATarget. RT-qPCR and VIGS were employed to identify the function of selected target transcripts. To confirm the interaction between vsiRNA and the target, 5′ RACE was performed to analyze the specific cleavage sites. Results From the sequencing data, we obtained a total of 11,384 detected vsiRNAs. The length distribution of these vsiRNAs was mostly 21 and 22 nt, and an A/U bias was observed at the 5′ terminus. We also observed that the production region of vsiRNAs had no strand polarity. The vsiRNAs were predicted to target 23,719 wheat transcripts. GO and KEGG enrichment analysis demonstrated that these targets were mostly involved in cell components, catalytic activity and plant-pathogen interactions. The results of RT-qPCR analysis showed that most chloroplast-related genes were downregulated in BYDV-GAV-infected wheat plants. Silencing of a chlorophyll synthase gene caused leaf yellowing that was similar to the symptoms exhibited by BYDV-GAV-inoculated wheat plants. A vsiRNA from an overlapping region of BYDV-GAV MP and CP was observed to target chlorophyll synthase for gene silencing. Next, 5′ RACE validated that vsiRNA8856 could cleave the chlorophyll synthase transcript in a sequence-specific manner. Conclusions This report is the first to demonstrate that BYDV-GAV-derived vsiRNAs can target wheat transcripts for symptom development, and the results of this study help to elucidate the molecular mechanisms underlying leaf yellowing after viral infection.

Abstract Although Psathyrostachys huashanica has excellent potential for resistance gene mining and molecular genetic breeding, no reference genome is available. To date, most studies of P. huashanica have been focused on the creation of translocation lines and additional lines, as well as the development of molecular markers. Therefore, research at the transcriptional level is lacking. In this study, the full-length transcriptome of P. huashanica was sequenced using PacBio isoform sequencing (Iso-Seq) of a pooled RNA sample to explore the potential full-length transcript isoforms. We obtained 112,596 unique transcript isoforms with a total length of 114,957,868 base pairs (bp). Subsequently, Illumina sequencing reads were used to correct and trim the PacBio isoforms. We annotated 103,875 unigenes in at least one functional database, and identified a plethora of differentially-expressed genes (DEGs) that are involved in the defense responses of P. huashanica against barley yellow dwarf virus-GAV (BYDV-GAV). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these DEGs were mostly involved in plant-pathogen interaction, plant hormone signal transduction, and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we selected twenty of the RNA-seq identified resistance-related up-regulated genes, including MAPKs, cysteine-rich receptor-like protein kinases (CRPKs), calcium-dependent protein kinases (CDPKs), pathogenesis-related protein (PR) proteins, WRKYs, and disease resistance proteins, and validated their up-regulation in response to BYDV-GAV by quantitative real-time PCR. Our results indicate that a series of defense-related genes were induced in P. huashanica during BYDV-GAV infection. The full-length transcriptome dataset will contribute to improved use of stress-resistance genes of P. huashanica, and serves as a reference database for the analysis of transcript expression in P. huashanica.

Farnesoid X receptor (FXR) is the nuclear receptor of bile acids and is involved in innate immune regulation. FXR agonists have been shown to protect multiple organs from inflammatory tissue injuries. Because liver expresses high levels of FXR, we explored the potential therapeutic benefits and underlying mechanisms of pharmacologic FXR activation in a murine model of partial liver warm ischemia. Pretreatment of mice with FXR agonist 3‐(2,6‐dichlorophenyl)‐4‐(3′‐carboxy‐2‐chlorostilben‐4‐yl)oxymethyl‐5‐isopropylisoxazole (GW4064) attenuated liver ischemia/reperfusion injuries (IRIs) in wild‐type but not FXR knockout mice. Posttreatment with GW4064 facilitated liver recovery from IRI. Mechanistically, Kupffer cells (KCs) expressed much higher levels of FXR than bone marrow‐derived macrophages (BMMs). Pretreatment of KCs but not BMMs with GW4064 resulted in lower tumor necrosis factor α but higher interleukin‐10 expressions following toll‐like receptor stimulation. FXR‐targeted gene small heterodimer partner (SHP) was critical for the regulation of KC response by GW4064. In vivo, the depletion of KCs but not cluster of differentiation (CD) 11b+ cells or knockdown of SHP diminished the immune regulatory effect of GW4064 in liver IRI. Thus, FXR activation protects liver from IRI by up‐regulating SHP in KCs to inhibit the liver proinflammatory response.

Introduction and objectives: Glucocorticoid resistance frequently associating with inflammation, may severely compromise the therapeutic effect of glucocorticoids. In this study, we aimed to investigate the regulation of glucocorticoid resistance by microRNA-124a (miR-124a) in patients with acute-on-chronic liver failure (ACLF). Materials and methods: The miR-124a levels and glucocorticoid receptor alpha (GRα) expressions in peripheral blood monocytes and liver tissues were measured by quantitative reverse transcription–polymerase chain reaction (qRT-PCR), flow cytometry, and western blot analyses in the following four groups: healthy controls (HC), moderate chronic hepatitis B (CHB) patients, hepatitis B virus-related ACLF (HBV-ACLF) patients, and alcohol-induced ACLF (A-ACLF) patients. In addition, the serum miR-124a levels and multiple biochemical indices were determined. The effects of miR-124a transfection on GRα expression were assayed by qRT-PCR and western blotting in U937 and HepG2 cells stimulated with lipopolysaccharide (LPS). Results: Compared with the CHB patients and HC, the miR-124a levels in HBV-ACLF and A-ACLF patients increased, while GRα expressions decreased. No significant differences in miR-124a levels and GRα expressions were observed between the HBV-ACLF and A-ACLF patients. For the ACLF patients, miR-124a level was negatively related to GRα expression in monocytes and positively correlated with the inflammatory factors such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). In U937 and HepG2 cells, LPS stimulated miR-124a levels but inhibited GRα expressions; meanwhile, increasing miR-124a levels reduced GRα expressions, and inhibiting miR-124a levels increased GRα expressions. Conclusions: This study provides evidence that GRα expression was negatively regulated by miR-124a, which primarily determines the extent of acquired glucocorticoid resistance in ACLF.

The main challenge in designing broadband achromatic metalenses is to achieve the desired phase distribution at different wavelengths and positions. Finding the exact relationship between phase modulation and the size or shape of individual nanopillars is a critical but time-consuming step. This paper presents a novel joint design framework predictive neural networks and particle swarm optimization-genetic algorithms, which combines predictive neural network (PNN) and particle swarm optimization-genetic algorithm (PSO-GA). The proposed framework aims to accurately predict the phase response of nanopillars using PNN, increase the number of phase data points to establish a one-to-one correspondence between the phase and nanopillar parameters in the design of broadband achromatic metalenses, and optimize the parameters of an individual nanostructure of the metalens using PSO-GA. To validate the efficacy of the proposed method, a broadband achromatic metalens for line polarization light in the range of 260–350 nm is designed. Numerical simulations demonstrate that the designed metalens exhibits achromatic focusing. The method proposed in this paper may find wider application in the design of more complex metasurface devices.

Abstract Tacrolimus (FK506) and rapamycin (RAPA) are widely used to maintain long‐term immunosuppression after organ transplantation. However, the impact of accumulative drug administration on the recipients’ immune systems remains unclear. We investigated the impact of 3‐year FK506 or RAPA treatment after renal transplantation on the human immune systems. A discovery cohort of 30 patients was first recruited, and we discovered two distinctive T lineage suppressive regulatory patterns induced by chronic treatment of FK506 and RAPA. The increased percentage of senescent CD8+CD57+ T lineages and less responsive T cell receptor (TCR) pathway in the FK506 group indicate better graft acceptance. Meanwhile, percentages of regulatory T cells (Tregs) and expression of CTLA‐4 were both up to two‐fold higher in the RAPA group, suggesting the inconsistent reactivation potential of the FK506 and RAPA groups when an anti‐tumour or anti‐infection immune response is concerned. Additionally, up‐regulation of phosphorylated signaling proteins in T lineages after in vitro CD3/CD28 stimulation suggested more sensitive TCR‐signaling pathways reserved in the RAPA group. An independent validation cohort of 100 renal transplantation patients was further investigated for the hypothesis that long‐term RAPA administration mitigates the development of tumours and infections during long‐term intake of immunosuppressants. Our results indicate that RAPA administration indeed results in less clinical oncogenesis and infection. The deep phenotyping of T‐cell lineages, as educated by the long‐term treatment of different immunosuppressants, provides new evidence for personalized precision medicine after renal transplantations.

Compressed sensing (CS) provides an innovative framework for signal sampling, which enables accurate recovery of the sparse or compressible signal from a small set of linear measurements far fewer than the Nyquist rate in traditional signal processing. In compressed sensing, random modulation plays a key role, which can spread out the signal information more or less evenly across all locations. There are many modulation techniques, such as amplitude modulation, frequency modulation, phase modulation, spectrum modulation, and so on. Among these modulation techniques, phase modulation is vital due to the efficiency and convenience of modulation. In this paper, we review both the theoretical and application of compressed sensing and several compressed imaging systems using random phase modulation. First, we review the fundamentals of compressed sensing, dividing it into three parts: sparse representation, incoherent measurement, and nonlinear reconstruction algorithm. We then show how phase modulation can be applied to compressed sensing and compressed imaging, where the presentation can be divided into six main parts, corresponding to different aspects of phase modulation applied in compressed sensing or compressed imaging: (1) Fundamentals of compressed sensing. (2) Principles of phase modulation. (3) Single-shot compressed imaging with spatial-domain single random phase mask (CI-SSRPM). (4) Single-shot compressed imaging with a random convolution using a double random phase mask (CI-DRPM). (5) Single-shot compressed imaging with Fourier-domain single random phase mask (CI-FSRPM). (6) Single-shot compressed imaging with double random phase encoding (CI-DRPE).

Abstract Background Myostatin antagonists are being developed as therapies for Duchenne muscular dystrophy due to their strong hypertrophic effects on skeletal muscle. Engineered follistatin has the potential to combine the hypertrophy of myostatin antagonism with the anti-inflammatory and anti-fibrotic effects of activin A antagonism. Methods Engineered follistatin was administered to C57BL/6 mice for 4 weeks, and muscle mass and myofiber size was measured. In the mdx model, engineered follistatin was dosed for 12 weeks in two studies comparing to an Fc fusion of the activin IIB receptor or an anti-myostatin antibody. Functional measurements of grip strength and tetanic force were combined with tissue analysis for markers of necrosis, inflammation, and fibrosis to evaluate improvement in dystrophic pathology. Results In wild-type and mdx mice, dose-dependent increases in muscle mass and quadriceps myofiber size were observed for engineered follistatin. In mdx, increases in grip strength and tetanic force were combined with improvements in muscle markers for necrosis, inflammation, and fibrosis. Improvements in dystrophic pathology were greater for engineered follistatin than the anti-myostatin antibody. Conclusions Engineered follistatin generated hypertrophy and anti-fibrotic effects in the mdx model.

Aims: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p

Abstract Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D+ and IFN-γ+ NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed. Serum and supernatant IFN-γ, TNF-α, perforin and granzyme B were measured. In results, peripheral NKG2D+ and IFN-γ+ NK cells frequencies, intrahepatic NKG2D and IFN-γ mRNA and protein levels, and serum IFN-γ, TNF-α, perforin and granzyme B levels were all highest in HBV-related acute-on-chronic liver failure group, followed by chronic hepatitis B and chronic HBV carrier groups. In vitro, NKG2D and IFN-γ mRNA and protein levels were higher in NK cells with IFN-α stimulation than without stimulation. Supernatant IFN-γ, TNF-α, perforin and granzyme B levels were increased under co-culture or IFN-α stimulating conditions, but were partially blocked by NKG2DmAb. In conclusion, NKG2D regulates immune inflammation and anti-viral response partly through activation of NK cells during HBV infection.

AFLP analyses were used to assess the genetic similarity among selected accessions at the South China Tobacco Breeding Research Centre (Yunnan province, Southwest China). 154 AFLP polymorphic fragments out of 561 fragments were used to assess the genetic diversity among 28 tobacco accessions. The average number of polymorphic bands per AFLP primer pair was 15.4. AFLPs seemed to be an effective classification tools for germplasm conservation and breeding. Limited genetic variation was detected within this group of accessions. The relationship of cultivars was estimated by cluster analysis based on AFLP data.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor because the molecular mechanisms underlying hepatocarcinogenesis are not well understood. In the study, we focused on identifying the role of miRNAs in HCC progression. miRNA microarray was used to analyze the differentially expressed miRNAs, and the results were validated by qPCR. We found that the miR-150-5p expression is down-regulated in HCC tissues compared with pair non-tumor tissues. miR-150-5p expression is also decreased in metastatic cancer tissues compared with pair primary tissues, indicating that miR-150-5p may be involved in HCC metastasis. Functionally, miR-150-5p inhibition significantly promotes hepatoma cell migration and invasion, whereas miR-150-5p overexpression suppresses cancer cell migration and invasion in vitro. The matrix metalloproteinase 14 (MMP14) is identified as a new target gene of miR-150-5p. miR-150-5p markedly inhibits MMP14 expression in hepatoma cells, and miR-150-5p expression is negative correlation with MMP14 expression in vivo. More important, re-expression of MMP14 in hepatoma cells partially reverses the effect of miR-150-5p in inhibiting cell invasion.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial. OBJECTIVE AND METHODS: Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay. RESULTS: Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). CONCLUSION: The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients.

BACKGROUND: Simvastatin exerts pleiotropic effects on cardiovascular system. However, its effect on non-alcoholic fatty liver disease, especially the liver fibrosis, remains obscure. We aimed to clarify the relationship between simvastatin and liver fibrosis both in vivo and in vitro. METHODS: A High-fat diet was given to establish rat models with non-alcoholic steatohepatitis (NASH)-related liver fibrosis and simvastatin (4mg·kg(-1)·d(-1)) was administrated intragastrically until hepatic histological findings confirmed the appearance of fibrosis. Human hepatic stellate cell (HSC) line lx-2 cells were cultured in an adipogenic differentiating mixture (ADM) and then were treated with transforming growth factorβ1 (TGF-β1), served as a positive control, simvastatin, TGF-β1 plus simvastatin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a inhibitor of nitric oxide synthase), and L-NAME plus simvastatin, respectively. The expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and Collagen І as well as cellular α-smooth muscle actin (α-SMA) were measured by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot in liver tissue and HSC. RESULTS: With the progress of NASH-related fibrosis, hepatic mRNA and protein expressions of iNOS, α-SMA, and Collagen І were increased while those of eNOS were decreased. Compared with model rats in 24(th) week group, rats in simvastatin group had less expressions of iNOS, α-SMA, and Collagen І and more expressions of eNOS. In vitro, LX-2 cells acquired quiescent phenotype when cultured in ADM, and TGF-β1 could activate the quiescent HSC. Simvastatin inhibited LX-2 cells activation due to TGF-β1 or L-NAME by increasing the expression of eNOS and decreasing the expression of iNOS. CONCLUSIONS: Simvastatin improves the prognosis of NASH-related fibrosis by increasing the expression of eNOS, decreasing the expression of iNOS, and inhibiting the activation of HSC.

BACKGROUND: Spontaneous acute exacerbation (AE) of chronic hepatitis B (CHB) is often detrimental but sometimes leads to sustained immune control and disease remission. The efficacy and safety of nucleos(t)ide analogues (NAs) in patients with spontaneous AE of CHB remains unclear. METHODS: We performed a systematic review and meta-analysis of NAs in patients with spontaneous AE of CHB. We calculated pooled effects of NAs in these patients of each study and conducted quantitative meta-analysis, displaying results using Forest plots. RESULTS: 15 studies were included and substantial heterogeneity was noted in the inclusion/exclusion criteria and controls. Pooled data showed no benefit of lamivudine (LAM) vs. untreated controls for transplant-free survival in patients with spontaneous AE of CHB (OR = 0.98 (95% CI, 0.50-1.92; P = 0.956)), hepatic decompensation (OR = 0.94 (95% CI, 0.47-1.88; P = 0.862)) and liver failure owing to AE (OR = 2.30 (95% CI, 0.35-15.37; P = 0.387)) at 3 months. Entecavir achieved even higher short-term mortality than LAM. NAs led to rates of ALT normalization, undetectable HBV DNA, HBeAg loss, HBeAg seroconversion and drug resistance at 1 year in 88%, 61%, 46%, 35% and 5%. Pooled data also showed benefit favoring LAM vs. untreated controls for ALT normalization (OR = 1.98 (95% CI, 1.03-3.80; P = 0.039)) and undetectable HBV DNA (OR = 38.50 (95% CI, 7.68-192.99; P

During normal development or during disease, animal cells experience hypoxic (low oxygen) conditions, and the hypoxia-inducible factor (HIF) transcription factors implement most of the critical changes in gene expression that enable animals to adapt to this stress. Here, we examine the roles of HIF-1 in post-mitotic aging. We examined the effects of HIF-1 over-expression and of hif-1 loss-of-function mutations on longevity in C. elegans, a powerful genetic system in which adult somatic cells are post-mitotic. We constructed transgenic lines that expressed varying levels of HIF-1 protein and discovered a positive correlation between HIF-1 expression levels and lifespan. The data further showed that HIF-1 acted in parallel to the SKN-1/NRF and DAF-16/FOXO transcription factors to promote longevity. HIF-1 over-expression also conferred increased resistance to heat and oxidative stress. We isolated and characterized additional hif-1 mutations, and we found that each of 3 loss-of-function mutations conferred increased longevity in normal lab culture conditions, but, unlike HIF-1 over-expression, a hif-1 deletion mutation did not extend the lifespan of daf-16 or skn-1 mutants. We conclude that HIF-1 over-expression and hif-1 loss-of-function mutations promote longevity by different pathways. These data establish HIF-1 as one of the key stress-responsive transcription factors that modulate longevity in C. elegans and advance our understanding of the regulatory networks that link oxygen homeostasis and aging.

The complexity of branching and curvilinear morphology of a complete mitochondrial network within each cell is challenging to analyze and quantify. To address this challenge, we developed an image analysis technique using persistent homology with a multiparameter filtration framework, combining image processing techniques in mathematical morphology. We show that such filtrations contain both topological and geometric information about complex cellular organelle structures, which allows a software program to extract meaningful features. Using this information, we also develop a connectivity index that describes the morphology of the branching patterns. As proof of concept, we utilize this approach to study how mitochondrial networks are altered by genetic changes in the Optineurin gene. Mutations in the autophagy gene Optineurin (OPTN) are associated with primary open-angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), and Paget's disease of the bone, but the pathophysiological mechanism is unclear. We utilized the proposed mathematical morphology-based multiparameter filtration and persistent homology approach to analyze and quantitatively compare how changes in the OPTN gene alter mitochondrial structures from their normal interconnected, tubular morphology into scattered, fragmented pieces. [ABSTRACT FROM AUTHOR]

Objectives: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME‐BLI) examination. Methods: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B‐type LSTs using ME‐BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B‐low (n = 178) and JNET2B‐high (n = 53) LSTs. The JNET2B‐low and JNET2B‐high LSTs were compared based on their histopathological and morphological classifications. Results: Among the 178 JNET2B‐low LSTs, 86 (48.3%) were histopathologically classified as low‐grade intraepithelial neoplasia, 54 (30.3%) as high‐grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B‐high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B‐low and JNET2B‐high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592–0.804) between the two endoscopists who reassessed the endoscopic images. Conclusion: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision‐making. [ABSTRACT FROM AUTHOR]