Regulated stepwise ESDPT mechanism associated with chalcogen substitutions in BDIBD derivatives.

Inspired by the brilliant photochemical and photophysical properties of organic molecules containing chalcogenide substitutions that could be potentially applied across various disciplines, in this work, the effects of the atomic electronegativity of chalcogens (O, S, and Se) on hydrogen bond interactions and excited state proton transfer (ESPT) are mainly focused. We present characteristic oxygen-hydroxybenzazole-substituted 2,5-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene-1,4-diol (BDIBD) derivatives that contain intramolecular double hydrogen bonds. The main objective of this study was to explore in detail the influence of the change of chalcogen atomic electronegativity on dual hydrogen bond interaction and ESPT behavior. By comparing the structural changes and infrared (IR) vibrational spectra of BDIBD derivative (BDIBD-O, BDIBD-S and BDIBD-Se) fluorophores in S0 and S1 states, combined with the preliminary detection of hydrogen bond interaction via the core-valence bifurcation (CVB) index and predicted hydrogen bonding energy (EHB), we conclude that dual hydrogen bonds should be strengthened in the S1 state, which is favorable for the occurrence of ESPT reactions. The charge recombination behavior of hydrogen bonds, induced by photoexcitation, further illustrates this point. By constructing potential energy surfaces (PESs) based on restrictive optimization and by searching the transition state (TS) structure, we finally elucidate stepwise excited-state double proton transfer (ESDPT). Specifically, we confirm that a change in atomic electronegativity has a regulatory effect on the ESDPT behavior in BDIBD derivatives, that is, lower atomic electronegativity is more conducive to stepwise ESDPT.

Dual Network Hydrogels Based on PRP and SA Promote the Retention Rate and Vascularization of Transplanted Fat.

BACKGROUND: Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. METHODS: We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. RESULTS: DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. CONCLUSIONS: DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat survival. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Spatially Asymmetric Nanoparticles for Boosting Ferroptosis in Tumor Therapy.

Despite its effectiveness in eliminating cancer cells, ferroptosis is hindered by the high natural antioxidant glutathione (GSH) levels in the tumor microenvironment. Herein, we developed a spatially asymmetric nanoparticle, Fe3O4@DMS&PDA@MnO2-SRF, for enhanced ferroptosis. It consists of two subunits: Fe3O4 nanoparticles coated with dendritic mesoporous silica (DMS) and PDA@MnO2 (PDA: polydopamine) loaded with sorafenib (SRF). The spatial isolation of the Fe3O4@DMS and PDA@MnO2-SRF subunits enhances the synergistic effect between the GSH-scavengers and ferroptosis-related components. First, the increased exposure of the Fe3O4 subunit enhances the Fenton reaction, leading to increased production of reactive oxygen species. Furthermore, the PDA@MnO2-SRF subunit effectively depletes GSH, thereby inducing ferroptosis by the inactivation of glutathione-dependent peroxidases 4. Moreover, the SRF blocks Xc- transport in tumor cells, augmenting GSH depletion capabilities. The dual GSH depletion of the Fe3O4@DMS&PDA@MnO2-SRF significantly weakens the antioxidative system, boosting the chemodynamic performance and leading to increased ferroptosis of tumor cells.

Bioactive decellularized adipose matrix prepared using a rapid, nonchemical/enzymatic method for adipogenesis.

Recent developments in the field of regenerative surgeries and medical applications have led to a renewed interest in adipose tissue-enriched mesenchymal stem cell scaffolds. Various advantages declared for the decellularized adipose matrix (DAM) have caused its extensive use in the transfer of stem cells or growth factors for soft tissue regeneration induction. Meanwhile, the long-term application of detergents toward DAM regeneration has been assumed as a risky obstacle in this era. Herein, a rapid, mechanical protocol was developed to prepare DAM (M-DAM) without chemicals/enzymes and was comprehensively compared with the ordinary DAM (traditional chemical method). Accordingly, this method could effectively hinder oils and cells, sustain the structural and biological elements, and contain a superior level of collagen content. In addition, more protein numbers, as well as higher basement membrane elements, glycoproteins, and extracellular matrix-related proteins were detected in the regenerated M-DAM. Also, superior adipogenesis and angiogenesis proteins were distinguished. The noncytotoxicity of the M-DAM was also approved, and a natural ecological niche was observed for the proliferation and differentiation of stem cells, confirming its great potential for vascularization and adipogenesis in vivo. The suggested technique could effectively prepare the modified DAM in variant constructions of tablets, powders, emulsions, hydrogels, and different three-dimensional-printed structures. Hence, this rapid, mechanical process can produce bioactive DAM, which has the potential to be widely used in various research fields of regenerative medicine.

Surface curvature-induced oriented assembly of sushi-like Janus therapeutic nanoplatform for combined chemodynamic therapy.

BACKGROUND: Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency. RESULTS: Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform. CONCLUSIONS: In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.

Comparative and phylogenetic analysis of complete chloroplast genome sequences of Salvia regarding its worldwide distribution.

Salvia is widely used as medicine, food, and ornamental plants all over the world, with three main distribution centers, the Central and western Asia/Mediterranean (CAM), the East Aisa (EA), and the Central and South America (CASA). Along with its large number of species and world-wide distribution, Salvia is paraphyletic with multiple diversity. Chloroplast genomes (CPs) are useful tools for analyzing the phylogeny of plants at lower taxonomic levels. In this study, we reported chloroplast genomes of five species of Salvia and performed phylogenetic analysis with current available CPs of Salvia. Repeated sequence analysis and comparative analysis of Salvia CPs were also performed with representative species from different distribution centers. The results showed that the genetic characters of the CPs are related to the geographic distribution of plants. Species from CAM diverged first to form a separate group, followed by species from EA, and finally species from CASA. Larger variations of CPs were observed in species from CAM, whereas more deficient sequences and less repeated sequences in the CPs were observed in species from CASA. These results provide valuable information on the development and utilization of the worldwide genetic resources of Salvia.

Mitofusin-2 gene polymorphisms and metabolic dysfunction associated fatty liver disease: a case-control study in a Chinese population.

OBJECTIVES: Mitofusion-2 (Mfn2) may have a role in mitochondrial oxidative stress and insulin resistance that can promote the development of metabolic dysfunction associated fatty liver disease (MAFLD). This retrospective and case control study aimed to explore the relationships between common Mfn2 single nucleotide polymorphisms (SNPs) and MAFLD in a northern Han Chinese population. METHODS: Six Mfn2 SNPs (rs2336384, rs873458, rs873457, rs4846085, rs2878677, and rs2236057) were genotyped using the ligase detection reaction in 466 MAFLD patients and 423 healthy controls. Genotype and allele frequencies were calculated, along with haplotype analysis and pairwise linkage disequilibrium. RESULTS: The genotype distribution of rs2336384, rs2878677, and rs2236057 among the MAFLD patients showed a significantly different pattern from that of healthy controls. The data showed that an increased risk of MAFLD was significantly correlated with patients carrying the GG genotype of rs2336384, CC genotype of rs873457, TT genotype of rs4846085, TT genotype of rs2878677, and the AA genotype of rs2236057. Moreover, The GGCTTA haplotype was found to be adversely linked with MAFLD by haplotype analysis. CONCLUSION: The current findings suggest a strong link between certain Mfn2 gene polymorphisms and MAFLD.

Heme oxygenase 1 alleviates nonalcoholic steatohepatitis by suppressing hepatic ferroptosis.

BACKGROUND: Heme oxygenase 1 (HO-1) has an influential but insufficiently investigated effect on ferroptosis, which is a novel form of programmed cell death and may play an effect on nonalcoholic steatohepatitis (NASH). However, the understanding of the mechanism is limited. Herein, our study aimed to explore the mechanism and role of HO-1 in NASH ferroptosis. METHODS: Hepatocyte conditional HO-1 knockout (HO-1HEPKO) C57BL/6J mice were established and fed a high-fat diet (HFD). Additionally, wild-type mice were fed either a normal diet or a HFD. Hepatic steatosis, inflammation, fibrosis, lipid peroxidation, and iron overload were assessed. AML12 and HepG2 cells were used to investigate the underlying mechanisms in vitro. Finally, liver sections from NASH patients were used to clinically validate the histopathology of ferroptosis. RESULTS: In mice, HFD caused lipid accumulation, inflammation, fibrosis, and lipid peroxidation, which were aggravated by HO-1HEPKO. In line with the in vivo results, HO-1 knockdown upregulated reactive oxygen species accumulation, lipid peroxidation, and iron overload in AML12 and HepG2 cells. Additionally, HO-1 knockdown reduced the GSH and SOD levels, which was in contrast to HO-1 overexpression in vitro. Furthermore, the present study revealed that the NF-κB signaling pathway was associated with ferroptosis in NASH models. Likewise, these findings were consistent with the liver histopathology results of NASH patients. CONCLUSION: The current study showed that HO-1 could alleviate NASH progression by mediating ferroptosis.

Multifunctional Janus Nanoplatform for Efficiently Synergistic Theranostics of Rheumatoid Arthritis.

Progress has been made in the application of nanomedicine in rheumatoid arthritis (RA) treatment. However, the whole process of monitoring and treatment of RA remains a formidable challenge due to the complexity of the chronic autoimmune disease. In this study, we develop a Janus nanoplatform (denoted as Janus-CPS) composed of CeO2-Pt nanozyme subunit on one side and periodic mesoporous organosilica (PMO) subunit on another side for simultaneous early diagnosis and synergistic therapy of RA. The Janus nanostructure, which enables more active sites to be exposed, enhances the reactive oxygen species scavenging capability of CeO2-Pt nanozyme subunit as compared to their core-shell counterpart. Furthermore, micheliolide (MCL), an extracted compound from natural plants with anti-osteoclastogenesis effects, is loaded into the mesopores of PMO subunit to synergize with the anti-inflammation effect of nanozymes for efficient RA treatment, which has been demonstrated by in vitro cellular experiments and in vivo collagen-induced arthritis (CIA) model. In addition, by taking advantage of the second near-infrared window (NIR-II) fluorescent imaging, indocyanine green (ICG)-loaded Janus-CPS exhibits desirable effectiveness in detecting RA lesions at a very early stage. It is anticipated that such a Janus nanoplatform may offer an alternative strategy of functional integration for versatile theranostics.

Site-specific anisotropic assembly of amorphous mesoporous subunits on crystalline metal-organic framework.

As an important branch of anisotropic nanohybrids (ANHs) with multiple surfaces and functions, the porous ANHs (p-ANHs) have attracted extensive attentions because of the unique characteristics of high surface area, tunable pore structures and controllable framework compositions, etc. However, due to the large surface-chemistry and lattice mismatches between the crystalline and amorphous porous nanomaterials, the site-specific anisotropic assembly of amorphous subunits on crystalline host is challenging. Here, we report a selective occupation strategy to achieve site-specific anisotropic growth of amorphous mesoporous subunits on crystalline metal-organic framework (MOF). The amorphous polydopamine (mPDA) building blocks can be controllably grown on the {100} (type 1) or {110} (type 2) facets of crystalline ZIF-8 to form the binary super-structured p-ANHs. Based on the secondary epitaxial growth of tertiary MOF building blocks on type 1 and 2 nanostructures, the ternary p-ANHs with controllable compositions and architectures are also rationally synthesized (type 3 and 4). These intricate and unprecedented superstructures provide a good platform for the construction of nanocomposites with multiple functionalities and understanding of the structure-property-function relationships.

Adverse Effect of Nonalcoholic Fatty Liver Disease on the Therapeutic Response in Patients with Chronic Hepatitis B.

Background and Aims: The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation. Methods: Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR). Results: We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR. Conclusions: In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

[Comprehensive evaluation of Pinellia ternata germplasm resources based on phenotypic trait classification].

The evaluation of germplasm resources is the prerequisite for the development, utilization, and conservation of Chinese medicinal resources. The selection of excellent germplasm is the key to the breeding and orderly production of Pinellia ternata. In this study, 21 germplasm materials of P. ternata from major production areas in China were collected and analyzed for population diversity after phenotypic preliminary screening. The results have revealed that the P. ternata population has abundant phenotypic variation, and the phenotypic changes could be divided into five phenotypes in terms of organ trait variation. Further analysis of variation in 20 quantitative traits of the population revealed that the coefficient of variation for adenosine content(339.05%) was the largest, while the coefficient of variation for the underground plant height(16.35%) was the smallest. Correlation analysis showed that there was a strong correlation among various traits, with 52 pairs of traits showing highly significant correlation(P<0.01) and 19 pairs of traits showing a significant correlation(P<0.05). The 21 germplasms in the test could be classified into three major clusters by cluster analysis, with Cluster Ⅱ having the highest number and content of nucleosides, making it suitable for the selection and breeding of P. ternata varieties with high content of nucleosides. The yield in Cluster Ⅲ was higher than that in other groups, making it suitable for the selection and breeding of P. ternata varieties with a high yield. All trait indicators could be simplified into five principal component factors through principal component analysis, and the cumulative contribution rate was up to 86.04%. Further, comprehensive analysis using membership function and stepwise regression analysis identified nine traits, such as plant height, main leaf length, and underground plant height as characteristic indicators for the comprehensive evaluation of germplasm resources of P. ternata. BX007, BX008, and BX005 were identified as germplasms with both high yield and high uridine content, with BX007 having the highest uridine content of 479.51 µg·g~(-1). It belonged to the germplasm of P. ternata with double bulbils and could be cultivated as a potential good variety. Based on the phenotypic classification of P. ternata, systematic resource evaluation was carried out in this study, which could lay a foundation for the excavation of genetic resources and the breeding of new varieties of P. ternata.

Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis.

OBJECTIVE: The aim of this study was to find novel biomarkers and develop a non-invasive, effective diagnostic model for hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis. METHOD: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to assess the expression of differentially expressed genes (AGRN, JAG1, CCL5, ID3, CCND1, and CAPN2) in peripheral blood mononuclear cells (PBMCs) from healthy subjects, chronic hepatitis B (CHB), and liver fibrosis/cirrhosis (LF/LC) patients. The molecular mechanisms underlying AGRN-regulated CHB were further explored and verified in LX2 cells, in which small interfering RNA (siRNA) was used to block AGRN gene expression. Finally, enzyme-linked Immunosorbent Assay (ELISA) was used to measure AGRN protein expression in 100 healthy volunteers, 100 CHB patients, and 100 LF/LC patients, and the efficacy of the diagnostic model was assessed by the Area Under the Curve (AUC). RESULTS: AGRN mRNA displayed a steady rise in the PBMCs of normal, CHB, and LF/LC patients. Besides, AGRN expression was markedly elevated in activated LX2 cells, whereas the expression of COL1 and α-SMA decreased when AGRN was inhibited using siRNA. In addition, downregulation of AGRN can reduce the gene expression of ß-catenin and c-MYC while upregulating the expression of GSK-3ß. Furthermore, PLT and AGRN were used to develop a non-invasive diagnostic model (PA). To identify CHB patients from healthy subjects, the AUC of the PA model was 0.951, with a sensitivity of 87.0% and a specificity of 91.0%. The AUC of the PA model was 0.922 with a sensitivity of 82.0% and a specificity of 90.0% when differentiating between LF/LC and CHB patients. CONCLUSION: The current study indicated that AGRN could be a potential plasma biomarker and the established PA model could improve the diagnostic accuracy for HBV-related liver diseases.

Cascading Alignment for Unsupervised Domain-Adaptive DETR with Improved DeNoising Anchor Boxes.

Transformer-based object detection has recently attracted increasing interest and shown promising results. As one of the DETR-like models, DETR with improved denoising anchor boxes (DINO) produced superior performance on COCO val2017 and achieved a new state of the art. However, it often encounters challenges when applied to new scenarios where no annotated data is available, and the imaging conditions differ significantly. To alleviate this problem of domain shift, in this paper, unsupervised domain adaptive DINO via cascading alignment (CA-DINO) was proposed, which consists of attention-enhanced double discriminators (AEDD) and weak-restraints on category-level token (WROT). Specifically, AEDD is used to aggregate and align the local-global context from the feature representations of both domains while reducing the domain discrepancy before entering the transformer encoder and decoder. WROT extends Deep CORAL loss to adapt class tokens after embedding, minimizing the difference in second-order statistics between the source and target domain. Our approach is trained end to end, and experiments on two challenging benchmarks demonstrate the effectiveness of our method, which yields 41% relative improvement compared to baseline on the benchmark dataset Foggy Cityscapes, in particular.

The genomic and bulked segregant analysis of Curcuma alismatifolia revealed its diverse bract pigmentation.

Compared with most flowers where the showy part comprises specialized leaves (petals) directly subtending the reproductive structures, most Zingiberaceae species produce showy "flowers" through modifications of leaves (bracts) subtending the true flowers throughout an inflorescence. Curcuma alismatifolia, belonging to the Zingiberaceae family, a plant species originating from Southeast Asia, has become increasingly popular in the flower market worldwide because of its varied and esthetically pleasing bracts produced in different cultivars. Here, we present the chromosome-scale genome assembly of C. alismatifolia "Chiang Mai Pink" and explore the underlying mechanisms of bract pigmentation. Comparative genomic analysis revealed C. alismatifolia contains a residual signal of whole-genome duplication. Duplicated genes, including pigment-related genes, exhibit functional and structural differentiation resulting in diverse bract colors among C. alismatifolia cultivars. In addition, we identified the key genes that produce different colored bracts in C. alismatifolia, such as F3'5'H, DFR, ANS and several transcription factors for anthocyanin synthesis, as well as chlH and CAO in the chlorophyll synthesis pathway by conducting transcriptomic analysis, bulked segregant analysis using both DNA and RNA data, and population genomic analysis. This work provides data for understanding the mechanism of bract pigmentation and will accelerate breeding in developing novel cultivars with richly colored bracts in C. alismatifolia and related species. It is also important to understand the variation in the evolution of the Zingiberaceae family. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00081-6.

Advances in molecular mechanisms underlying cadmium uptake and translocation in rice.

The increasing cadmium (Cd) pollution in paddy fields has severely threatened China's ecological and food safety. Cultivation of low Cd accumulation varieties to reduce Cd content in rice or cultivation of Cd-tolerant varieties for phytoremediation are considered effective methods to control Cd pollution in paddy fields. However, the underlying molecular mechanism of Cd absorption and transport by rice plants needs to be deciphered to cultivate these varieties. Here, we summarized the molecular mechanisms underlying Cd absorption and transport in rice, as well as the variation of Cd accumulation among rice varieties, the QTLs related to Cd accumulation in rice, and discusses the direction of future research.

Versatile synthesis of dendritic mesoporous rare earth-based nanoparticles.

Rare earth-based nanomaterials that have abundant optical, magnetic, and catalytic characteristics have many applications. The controllable introduction of mesoporous channels can further enhance its performance, such as exposing more active sites of rare earth and improving the loading capacity, yet remains a challenge. Here, we report a universal viscosity-mediated assembly strategy and successfully endowed rare earth-based nanoparticles with central divergent dendritic mesopores. More than 40 kinds of dendritic mesoporous rare earth-based (DM-REX) nanoparticles with desired composition (single or multiple rare earth elements, high-entropy compounds, etc.), particle diameter (80 to 500 nanometers), pore size (3 to 20 nanometers), phase (amorphous hydroxides, crystalline oxides, and fluorides), and architecture were synthesized. Theoretically, a DM-REX nanoparticle library with 393,213 kinds of possible combinations can be constructed on the basis of this versatile method, which provides a very broad platform for the application of rare earth-based nanomaterials with rational designed functions and structures.

Identification and Validation of Novel Biomarkers for Hepatocellular Carcinoma, Liver Fibrosis/Cirrhosis and Chronic Hepatitis B via Transcriptome Sequencing Technology.

Purpose: The aim of this study was to identify and validate novel biomarkers for distinguishing among hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB). Patients and Methods: Transcriptomic sequencing was conducted on the liver tissues of 5 patients with HCC, 5 patients with LF/LC, 5 patients with CHB, and 4 healthy controls. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining, and were verified in validation set (n=200) and testing set (n=400) via enzyme-linked immunosorbent assay (ELISA). Results: A total of 9 hub mRNAs were identified by short time-series expression miner and weighted gene co-expression network analysis. Of note, the results of qRT-PCR and IHC staining demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited gradually increasing trends in the four groups. Subsequent ELISA tests on the validation cohort indicated that the plasma levels of SHC1, SLAMF8 and IL-32 also gradually increased. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish among CHB, LF/LC and HCC. The performance of APFSSI model for discriminating CHB from healthy subjects (AUC=0.966) was much greater compared to SHC1 (AUC=0.900), SLAMF8 (AUC=0.744) and IL-32 (AUC=0.821). When distinguishing LF/LC from CHB, APFSSI was the most outstanding diagnostic parameter (AUC=0.924), which was superior to SHC1, SLAMF8 and IL-32 (AUC=0.812, 0.684 and 0.741, respectively). Likewise, APFSSI model with the greatest AUC value displayed an excellent performance for differentiating between HCC and LF/LC than other variables (SHC1, SLAMF8 and IL-32) via ROC analysis. Finally, the results in the test set were consistent with those in the validation set. Conclusion: SHC1, SLAMF8 and IL-32 can differentiate among patients with HCC, LF/LC, CHB and healthy controls. More importantly, the APFSSI model greatly improves the diagnostic accuracy of HBV-associated liver diseases.

Contribution of K solubilising bacteria (Burkholderia sp.) promotes tea plant growth (Camellia sinesis) and leaf polyphenols content by improving soil available K level.

K+ availability is important for growth and quality of tea (Camellia sine sis L.). K solubilising bacteria convert insoluble K to available K. This study was conducted to screen K solubilising bacteria isolated from tea rhizosphere soil in Qimen county, Anhui province, China. The maximum K solubilisation colony (the ratio of diameter halo/colony was 2.54) was identified as Burkholderia sp. (storage number: M2021105) by biochemistry and molecular analysis. Pot experiments (Laterite) showed that the inoculation of Burkholderia sp. significantly improved tea plant height (Zhongcha108, 1 year old) and total polyphenols content by 21.14% and 21.58% compared with the control, respectively. Higher polyphenol level promoted the formation of theaflavin in the fermentation experiments. Further experiments showed that tartaric acid and pryuvic acid produced by Burkholderia sp. are important components associated with K solubilisation in vitro . Burkholderia sp. significantly increased soil available K by 15.12%; however, there was no significant difference in available N and P, and Cu, Mg, Zn and Ca compared with the control. K content in inoculated tea roots and leaves was significantly higher (50% and 10%, respectively) than the control. Compared with the control, exogenous supply of 60mgkg-1 K significantly increased levels of polyphenol (53.97%), theaflavin (16.31%), theaflavin-3-gallate (20%), theaflavin 3'-gallic acid ester (32.24%) and theaflavin 3,3'-gallic acid ester (40.95%). Due to its ability to enable higher available soil K, ur study indicated that Burkholderia sp. have potential to increase total polyphenols content be a bio-inoculant for biofortification of tea.

Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling.

BACKGROUND/AIMS: The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. MATERIALS AND METHODS: Wistar rats were used to generate a model of carbon tetrachloride (CCl4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. RESULTS: YQHX markedly alleviated morphological alterations in CCl4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl4-meidated activation of the transforming growth factor-beta (TGF-ß)/Smad signaling pathway. Notably, CCl4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P = 0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. CONCLUSION: YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis.